The FDA has approved a supplemental new drug application to add overall survival (OS) and other secondary end point data from the phase 3 ARAMIS trial (NCT02200614) to the prescribing information for darolutamide (Nubeqa) for the treatment of patients with nonmetastatic prostate cancer (nmCRPC).

Darolutamide led to a 31% reduction in the risk of death, extending survival for patients with nmCRPC (HR, 0.69; 95% CI, 0.53-0.88; P = .003).

 The additional findings comprise time to pain progression (HR, 0.65; 95% CI, 0.53-0.79; P <.0001) and time to the initiation of cytotoxic chemotherapy (HR, 0.58; 95% CI, 0.44-0.76; P <.0001).

Moreover, the prescribing information was also updated to include additional guidance on drug interactions. The final analysis of the trial reinforced the safety profile of darolutamide with an extended follow-up of median 29 months for the overall study population.

"A key goal of cancer treatment is to ensure that patients can live longer while minimizing side effects," said Scott Z. Fields, MD, senior vice president and head of Oncology Development at Bayer's Pharmaceutical Division. “[Darolutamide] has a proven efficacy and safety profile in men with nmCRPC and delayed the effects of disease progression in men who are otherwise generally asymptomatic. This update also gives physicians added certainty that [darolutamide] should be prescribed to appropriate patients at nmCRPC diagnosis to help ensure optimal outcomes for these men.”

In July 2019, the FDA approved darolutamide for the treatment of patients with nmCRPC based on data from ARAMIS, which showed that the combination of the androgen receptor inhibitor plus ADT resulted in a 59% reduction in the risk of metastases or death versus placebo/ADT in this population (n = 1509; HR, 0.41; 95% CI, 0.34-0.50; 2-sided P <.0001).

 The median MFS was 40.4 months in those who received darolutamide plus androgen deprivation therapy (ADT; n = 955) versus 18.4 months with placebo/ADT (P <.001).

In the multicenter, double-blind, placebo-controlled, randomized phase 3 trial, investigators examined the safety and efficacy of darolutamide in patients with nmCRPC who were on standard ADT and at high risk for developing metastatic disease. Participants were randomized 2:1 to receive darolutamide at a twice-daily dose of 600 mg in combination with ADT or placebo/ADT.

All patients had an ECOG performance status of 0-1. The primary end point of ARAMIS was MFS, while secondary end points comprised OS, time to pain progression, time to initiation of first cytotoxic chemotherapy, time to first symptomatic skeletal event, and characterization of safety and tolerability.

Data for OS had been immature at the time of the primary analysis. At a median follow-up of 29.0 months, the OS at 3 years was 83% (95% CI, 80-86) and 77% (95% CI, 72-81) in the investigational and control arms, respectively.

The OS benefit with darolutamide/ADT still proved to be statistically significant despite 31% (n = 170) of patients in the placebo/ADT having crossed over to the investigational arm. Overall, 55% of patients (n = 307) in the control arm ended up crossing over to darolutamide/ADT or went on to receive another life-prolonging treatment prior to the analysis.

Fifty-five percent of patients on the control arm received subsequent treatment with darolutamide or other life-prolonging therapy. Of 384 patients in the placebo group who had discontinued treatment prior to the unblinding of the data, 137 were given a subsequent life-prolonging treatment beyond darolutamide; these included docetaxel, abiraterone acetate (Zytiga), and enzalutamide (Xtandi). In the investigational arm, 15% of 955 patients were given subsequent treatment beyond darolutamide.

Additional results indicated that darolutamide/ADT resulted in a significantly longer time to pain progression compared with placebo/ADT, at 40.3 months versus 25.4 months, respectively. At 3 years, the percentage of participants who had not yet received their first cytotoxic chemotherapy was 83% versus 75% of those in the investigational and control arms, respectively.

Moreover, the percentage of patients who had not experienced a first symptomatic skeletal event was 96% versus 92%, respectively, at 3 years. The time to first symptomatic skeletal event was significantly improved with darolutamide (HR, 0.48; 95% CI, 0.29-0.82; P = .005).

Regarding safety, 85.7% of patients who received darolutamide/ADT experienced toxicities versus 79.2% of those on placebo/ADT in the double-blind treatment period; 70.0% of patient who crossed over during the open-label period also experienced adverse effects (AEs). In the darolutamide/ADT arm, 8.9% of patients discontinued treatment versus 8.7% of patients in the placebo/ADT arm. Incidence of serious AEs and grade 5 toxicities in the investigational and control arms proved to be consistent with what had previously been revealed in the primary analysis.

1. US FDA approves addition of overall survival and other secondary endpoint data to Nubeqa (darolutamide) prescribing information. News release. Bayer. January 8, 2021. Accessed January 8, 2021. http://bwnews.pr/2XAIhDL.

2. Nubeqa (darolutamide tablets). Prescribing information. Bayer; 2021. Accessed January 8, 2021.

3. Fizazi K, Shore N, Tammela TL, et al. Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. N Engl J Med. 2020;383(11):1040-1049. doi:10.1056/NEJMoa2001342.

This article was originally posted on OncLive as, "

FDA Updates Label for Darolutamide in Nonmetastatic CRPC to Include OS Data

Articles

FDA Updates Darolutamide Label for Prostate Cancer

The FDA has approved the oral gonadotropin-releasing hormone (GnRH) receptor antagonist relugolix (Orgovyx) as a treatment for patients with advanced prostate cancer.

The regulatory decision was based on data from the pivotal phase 3 HERO trial, where relugolix showcased superiority over leuprolide (Lupron) in terms of sustained testosterone (T)-suppression through 48 weeks, fast T-recovery following discontinuation, and a 50% reduction in major adverse cardiovascular events (MACE) in patients with advanced disease.

In the international, 48-week, phase 3 trial, a total of 934 patients with androgen-sensitive advanced prostate cancer were randomized in a 2:1 fashion to either oral relugolix at a once-daily dose of 120 mg following a one-time 360 mg loading dose (n = 624) or a 3-month depot injection of leuprolide acetate (n = 310). In a subset of 184 patients, investigators examined testosterone recovery.

To be eligible for enrollment, patients to have confirmed advanced prostate cancer, have received at least 1 year of androgen deprivation therapy (ADT), a serum prostate-specific antigen higher than 2.0 ng/mL, and an ECOG performance status of either 0 or 1.

If patients were expected to receive chemotherapy or undergo surgery within 2 months of ADT administration, had previous ADT for longer than 18 months for prior systemic cytotoxic treatment for their disease, had active liver disease, or severe cardiovascular risk conditions, they were excluded from the trial.

A total of 563 patients who received relugolix completed treatment versus 276 patients who received leuprolide. Additionally, 9.5% of patients in the investigational arm versus 10.3% in the control arm discontinued treatment early. The remaining participants underwent randomization but they did not receive treatment.

Baseline characteristics were found to be balanced between the arms. Approximately 50% of patients who enrolled on the trial experienced biochemical recurrence following definitive treatment for prostate cancer. Moreover, 28.9% of patients were enrolled in North America and 11.5% were enrolled in Japan. Almost all patients, or over 90%, had at least 1 cardiovascular risk factor.

Additional data demonstrated that 96.7% (95% CI, 94.9%-97.9%) of patients who were given relugolix achieved and maintained castration through 48 weeks compared with 88.8% of those who received leuprolide. The 7.9%-difference (95% CI, 4.1%-11.8%) showed noninferiority (margin — 10%) and superiority (P <.0001) of relugolix to leuprolide. Notably, all secondary end points evaluated also showcased superiority for relugolix over leuprolide (P <.0001).

In those who were assessed for testosterone recovery, median T-levels in the relugolix and leuprolide arms were 270.76 ng/dL and 12.26 ng/dL, respectively, 90 days following discontinuation of treatment.

Updated data from HERO showed that relugolix was not found to achieve statistical superiority with regard to castration resistance—free survival compared with leuprolide through 48 weeks in this population.4 Specifically, 74% of patients with metastatic disease in the relugolix arm were castration resistance free in this time period versus 75% of those in the leuprolide arm (HR, 1.03; 95% CI, 0.68-1.57; P = .84).

With regard to safety, MACE incidence was found to be lower in the investigational arm versus the control arm, at 2.9% versus 6.2%, respectively. The rest of the profiles of the 2 agents proved to be comparable with the exception of that factor.

Specifically, toxicities experienced by more than 10% of patients who received relugolix or leuprolide included hot flash (54.3% vs 51.6%, respectively), fatigue (21.5% vs 18.5%), constipation (12.2% vs 9.7%), diarrhea (12.2% vs 6.8%), arthralgia (12.1% vs 9.1%), and hypertension (7.9% vs 11.7%). Diarrhea reported on the trial was only grade 1 or 2 and did not lead to treatment discontinuation.

1. FDA approves first oral hormone therapy for treating advanced prostate cancer. News release. FDA. December 18, 2020. Accessed December 18, 2020. http://bit.ly/2Ws5nvz.

2. Shore ND, George DJ, Saad F, et al. HERO phase III trial: results comparing relugolix, an oral GnRH receptor antagonist versus leuprolide acetate for advanced prostate cancer. J Clin Oncol. 2020;38(suppl 15):5602. doi:10.1200/JCO.2020.38.15_suppl.5602

3. Shore ND, Saad F, Cookson MS, et al. Oral relugolix for androgen-deprivation therapy in advanced prostate cancer. N Engl J Med. 2020;382(23):2187-2196. doi:10.1056/NEJMoa2004325

4. Myovant Sciences announces results of additional secondary endpoint of castration resistance-free survival from phase 3 HERO study of relugolix in advanced prostate cancer. News release. Myovant Sciences. September 29, 2020. Accessed December 3, 2020. https://bit.ly/3cFMooy.

This article was originally published on OncLive. 

FDA Approves Orgovyx for Advanced Prostate Cancer Treatment

The FDA approved Gallium 68 PSMA-11 (Ga 68 PSMA-11), a drug for PET imaging of prostate-specific membrane antigen (PSMA) positive levels in men with suspected prostate cancer metastasis, who may be curable by surgery or radiation therapy.

Ga 68 PSMA-11, which can also be used for patients with suspected prostate cancer recurrence, based on PSA levels, is a radioactive diagnostic agent given via intravenous injection. The drug can help determine treatment decisions, and spare individuals from unnecessary surgery.

“Ga 68 PSMA-11 is an important tool that can aid health care providers in assessing prostate cancer,” said Alex Gorovets, MD, acting deputy director of the Office of Specialty Medicine in FDA’s Center for Drug Evaluation and Research, in a statement.

GA 68 PSMA-11 binds to PSMA — an antigen that usually occurs in elevated levels for men with prostate cancer. The radioactive drug emits positrons and can be seen on a PET scan, thus indicating prostate cancer within the body.

The drug was evaluated in 2 prospective clinical trials, including a total of 960 men who each had 1 injection of Ga 68 PSMA-11. In the first trial, men with positive readings in their pelvic lymph nodes on Ga 68 PSMA-11 PET had a clinically meaningful rate of metastatic cancer that was confirmed by surgical pathology.

The second study involved patients with rising serum PSA levels after prostate surgery or radiotherapy. Nearly three-fourths (74%) had at least 1 positive cancer lesion detected by Ga 68 PSMA-11. Local recurrence or metastasis was confirmed in 91% of patients.

There were no major adverse events with Ga 68 PSMA-11. Common reactions included nausea, diarrhea, and dizziness. Additionally, clinicians should be aware that there is a risk of misdiagnosis if the agent binds to non-malignant cells.

“With this first approval of a PSMA-targeted PET imaging drug for men with prostate cancer, providers now have a new imaging approach to detect whether or not the cancer has spread to other parts of the body.”

The FDA approved Gallium 68 PSMA-11 (Ga 68 PSMA-11), a drug for PET imaging of prostate-specific membrane antigen (PSMA) positive levels in men with suspected prostate cancer metastasis, who may be curable by surgery or radiation therapy.
 

FDA Approves PSMA-Targeted Imaging Drug for Prostate Cancer

Our expert faculty spoke to nurses, patients and caregivers regarding clinical trials, advancements in treatment, and managing side effects. A special topic of discussion was for nurses, focusing on their role in supporting patients with bladder cancer.

Live on the webinar, participants also had the opportunity to submit questions to be answered live by our expert panel.

Developments in treatment of advanced bladder cancer

Managing side effects of cancer treatment

Multi-faceted role of nurses supporting patients with cancer.

MS. KRISTIE KAHL:  Hi, everyone.  Welcome to today's live broadcast of the CURE Educated Patient Webinar in Advanced Bladder Cancer.  I'm Kristie Kahl, Editorial Director of CURE.  We're pleased to bring you this webcast, presented by CURE, and in partnership with the Bladder Cancer Advocacy Network, Estellos Pharma, and CGEN. 

We have a few important announcements before we begin.  We encourage you to ask questions during the event, which you can submit by typing them into the Q&A box.  You will be receiving a survey via email tomorrow.  As a thank you for watching the full webinar and completing our survey, you'll be entered to win one of three Visa gift cards.

We're pleased to be joined today by our moderator, Dr. Jonathan Rosenberg, Chief of the Genitourinary Oncology Service at Memorial Sloan-Kettering Cancer Center, Ms. Asia McCoy, Clinical Trials Nurse at Memorial Sloan-Kettering Cancer Center, and Ms. Karen Sasche, sorry, Sasche, a patient advocate at the Bladder Cancer Advocacy Network.  Thank you for joining us today, and we will now pass off to our moderator to begin the discussion.

DR. JONATHAN ROSENBREG:  Thank you so much, and it has been a pleasure to be here today with you.  So, I'm going to first start out talking a little bit about what the standard of care is for advanced bladder cancer, and then we'll talk about--and we think about taking care of patients, both on clinical trials, and with standard treatments, and think about it from the patient perspective and the patient advocate perspective as well.

So, when we think about patients with metastatic bladder cancer, we have to consider that the standard of care still remains chemotherapy as the first line treatment for most patients.  There have been several large clinical trials that have recently showed us that chemotherapy is not beaten by immunotherapy; that in fact, for most patients, chemotherapy is the best place to start, and the standard regimens usually are gemcitabine with a platinum drug, although there are some patients who are getting chemotherapy regimens, such as MVAC.

We know that from other trials that have been done recently, that if you have chemotherapy and you do well, that you can go on to get immunotherapy as a maintenance treatment, after you complete your first line chemotherapy, because we know those patients live longer and do better, and actually had a fairly substantial improvement in the average survival for patients who get immunotherapy.

We also know that some patients whose tumors express very high levels of PDL-1, which is a target of the immune drugs, the immune checkpoint drugs, that they may be patients who may get immunotherapy in the front line setting instead of chemotherapy, and that's the discussion you have to have with your doctor.  It's a somewhat subtle discussion around what options might be appropriate for you if you're first diagnose with advanced cancer, and then for patients where chemotherapy or immunotherapy has stopped working, we have two new drugs that are very exciting

One is a drug called enfortumab vedotin, which is something called an antibody drug conjugate, which basically takes chemotherapy and attaches it to an antibody that's targeted to a molecule on the surface of cancer cells, and selectively delivers it to the bladder cancer cells preferentially above all the other cells in the body, reducing the side effect profile of the medicine for patients, and so that is a new treatment that was just FDA-approved a little under a year ago, done inexpensively [phonetic] in clinical trials, and also another drug erdafitinib, which is an oral medication targeting a molecule called FGFR3, or the fibroblast growth factor receptor 3, and that drug is a pill taken once a day by patients who have mutations in that gene, and it's about 15 to 20 percent of patients who have metastatic bladder cancer, will have those mutations in the genes of their cancer, and might be candidates to use that.

But when we're thinking about the types of treatments for advanced cancer, we really have to consider the patient in front of us, and the medical conditions they have, the comorbidities that they have, the limitations, functionally or other ways in their life that they may have, and so Asia, when we're thinking about putting people on clinical trials or on other treatments, how do you engage a patient around some of these issues around side effects, and how we might guide patients as far as treatment?

MS. ASIA MCCOY:  So, I have to agree with you, Dr. Rosenberg, in terms of looking at the big picture when it comes to patients, and nurses are really pros at that, so one of the more significant things that I like to zero in on is, if the patient has been treated with anything in the past, whether that has been surgery or radiation therapy, if they've had chemo, if they've had some type of targeted drug, and now, you know, the landscape has been really changed with the introduction of immunotherapy drugs that we're using for bladder cancer, and also targeted therapy, and another thing that we have to consider, too, is the identification of mutations, where we can introduce targeted [break in audio].

     You also want [break in audio] functional statuses.  Is this someone that is still working, still maintaining their regular lifestyle, or is this someone who needs assistance to do everything, including activities and daily living, so, you know, is cooking a chore for them, is bathing a chore for them, is getting dressed a chore for them?  You want to kind of incorporate treatment and potential side effects to round out this picture and eventually come to the best therapy for the patient.

DR. ROSENBERG:  And it's important in that context, really - - , what's actually happening in the patient's life, who's helping them, who do they have as resources, do they need help, are they completely independent?  Some people want to be independent, but maybe actually aren't able to handle it, and identifying those, and finding the resources, and that's where our nursing colleagues are very good at sussing a lot of that out, in fact, probably better than a lot of doctors are, I would say.

     What--in terms of communication between doctors and patients, Karen, you've been on both sides of this, perhaps uniquely, and what advice do you have for physicians and nurses and other healthcare providers to really understand the advances in treatment and how it affects patients.

MS. KAREN SACHSE:  Well, the thing I really want to zero in on is the fact that information that you're talking about in the session with the family, it needs to be written down, because I have to tell you how many times I went home, and I was there as eyes and ears for my husband, and I went home, and it was like, now, what was that drug, what was it all about, and so having it written down, and having it in simple language, even though patients are--may have gone to college, or are very sophisticated, when they're sick and when they're stressed out, they have a very difficult time interpreting high level language, so keeping it very simple and in plain English, I would say, is really important.

DR. ROSENBERG:  Yeah, I spent a lot of time training fellows, and one of the things that I harp on with them is that, don't use jargon, explain it to the patient as if you'd explain it to your parents or your siblings, because it's very easy to--you lose people very quickly that way, and it's--our job is really--in addition to treating patients, is to really educate them about the treatment, about the disease, and about their options, and if they walk out of the room with their head spinning, it's not a good experience for anybody, unfortunately, and only will prompt more questions the next day.

So, what do you--how do you counsel patients--let's say patients come to you asking, where can I get information, and how can we--and are there resources, Asia, that you point them to, or Karen, that you found useful?

MS. MCCOY:  Oh, definitely.  At our institution, we have a patient education resource section, and that's where all of our patient education fact cards live, so when we're doing education with patients, we have them referenced there--they signed off on, it's really like a guideline whenever they're going on study, and I'm using the term, informed consent, because my specialty is clinical trials.  I am a clinical trials nurse at Memorial Sloan-Kettering Cancer Center, and that document is written in layman's terms, really easy language to comprehend and break down and understand, so we have that compiled with the patient education fact cards that are also written in layman's terms, and those speak to the drugs that they're going to be treated with, if it's something that is approved by the Food and Drug Administration.

If it is an investigational drug that is not approved by the FDA, then that onus is on the clinical trials nurse to break down how that drug works, and then we also have Beacon as a resource.  I've given that information to many patients who have gone online and gotten a lot of resources, joined groups, some are even interested in becoming patient advocates, so as much as you can give, and also assessing the need, because as Karen stated, writing down things was really beneficial for her in her situation.

So, patients learn in different ways.  Sometimes they are visual learners.  They like to actually see things, or they like to hear things, so if we have those resources, it is upon--it's on the nurse to make sure that we can connect the patient and their caregiver with that information, also making sure that a second party or third party is available.  It's always really good to have a second set of eyes and a second set of ears, so if a patient comes in on their own, and they express to me that they're not confident with intaking all the information that we're giving, we will get somebody on the phone, or get somebody on Facetime to kind of take notes or listen in, so there's more than one individual getting that information.

DR. ROSENBERG:  Karen, anything you want to add?

MS. SACHSE:  I just want to say, one of the things that I did that was really helpful was, I put together a notebook, and had it labeled, different sections for lab work, for appointments, I mean, I took notes at every appointment--

DR. ROSENBERG:  [Crosstalk] medical charts.

MS. SACHSE:  Yeah, and you know, I mean, in the clinic where we were, their record was not computerized at the time, and so it was actually very helpful for the nurses to have all that information, because I had it right at my fingertips, but then all the handouts that the nurses would give us went in that notebook, and it was--just helped me stay organized, and I brought it to every appointment, and it was like my bible.

DR. ROSENBERG:  Yeah, those are very helpful when patients--not every patient, I think, works--is as organized as you are, would be, or were, but those are actually very helpful for the doctor when the patient walks in with a binder and says--especially if it's someone who gets part of their care in other places, oh, this was done on this date, and they just flip through it and show it to you, and you don't have to reinvent the wheel, but that puts the onus--that's great if they can do that, I don't want to put the onus on them for it.

MS. SACHSE:  Well, I know, and the other thing that was really helpful is, I learned to get copies of the scans, and so I would bring those around to different providers, because as with bladder cancer, it's multi-disciplinary, and different specialists, and so again, it really came in handy, and it was really helpful to the providers.

DR. ROSENBERG:  I can imagine.  So, I wanted to shift gears a little bit and talk about some side effects.  I wanted to just briefly review some of the types of side effects we see from the types of treatments that we are currently giving for advanced bladder cancer, for metastatic bladder cancer.  So, for patients who receive chemotherapy, some of our medications lead to peripheral neuropathy, which can mean numbness and tingling in the fingers or the toes.  That can be progressive in some patients, annoying in most patients if it happens, and sometimes, really affect quality of life and mobility if it gets severe.

Other side effects often include fatigue, which is unfortunately a side effect of many types of cancer treatments, not only chemotherapy.  In addition, patients who get chemotherapy are at risk for infection, often because their white blood cells may become very low, and their neutrophils, which are the infection-fighting cells, may be catastrophically low, very, very low,

For patients who are receiving immunotherapy as the mainstay of treatment, so these are the IV medications that are antibodies targeting molecules on the surface of immune cells, that these medications actually can trigger autoimmunity, where your body is attacking itself in ways that are sometimes predictable, and other times very unpredictable, and what I tell patients is that probably a third of patients have few or no side effects if they're getting single drug immunotherapy.  About another 40 or 50 percent of patients have mild to moderate side effects that can be managed pretty easily, and then anywhere from 10 to 20 percent of patients may have more severe side effects that could require hospitalization or high doses of immunosuppression, and then very, very rarely, people can die from side effects, both chemotherapy or immunotherapy, or any cancer treatment.  It is a very rare event, but unfortunately, it does occur.

For patients receiving the antibody drug conjugate, enfortumab vedotin, neuropathy, fatigue, and high blood sugar are issues that we see, and for patients receiving the targeted therapy, erdafitinib, you can get mouth sores, changes in the fingernails, and it also raises your blood phosphorus levels, which have to be monitored and dealt with if they get very high.

So, side effects, there's no free lunch in cancer treatments, unfortunately.  I wish there was; it would make all of our days much easier, and patients much happier, but while we work towards less toxic treatments, we've learned how to manage a lot of these things, and ameliorate them or adjust doses and modify treatments, and really, frankly, the oncology nurses are at the forefront of this, both clinical trials and not clinical trials oncology nurses.  Asia, how do you go about assessing these things when you see patients in terms of how they're doing, and in terms of what things you want to focus on with the doctor about the patient, and with the patient?

MS. MCCOY:  So, from having a special knowledge, experience [break in audio] these therapies, you kind of know how to zero in and ask the right questions and peel back the layers to kind of figure out what's going on with a patient.  Sometimes, patients and their caregivers are very, very detailed; they will let you know everything that's happening at every moment, and then you have another [break in audio] patient - - to try to get that information out of them, to try to help and to try to intervene, so really having a focus assessment depending on what drug the patient is being treated with, and also a knowledge, having a knowledge of that particular patient.

It's almost like treating a patient like they're in a silo, even though you may have several patients who are on that clinical trial, so with knowing all of those things, you kind of know how to pick and pull, get to the bottom of the situation, and discuss it with the disease management team to come up with the best solution and best intervention to help the patient and manage the patient.

DR. ROSENBERG:  And as a patient, do you have to be - - , to describe what your symptoms are and let the team taking care of you know about them, it's--we really try--people try--you try to ask all the questions, but sometimes, we don't get to the heart of it as well as we good, if the patient is not willing to be forthcoming about what's happening.

MS. MCCOY:  I have to say, that's something that we focus on, too, on patient education, not to cut you off, Dr. Rosenberg, but we try to make a stamp and a note of letting the patient and their caregivers know that this is a 50/50 partnership.  We're here to treat them, keep them safe while we're treating them, manage any side effects or symptoms, but it is their responsibility to know what's going on, what's happening with the drug that they're being treated with, to monitor themselves, to care for themselves, and to also communicate with us and not wait to communicate.  Because if we can fix it at the very beginning, instead of it escalating and getting to a point where we have to fix the problem and hold off on your treatment, we would much rather do that.

DR. ROSENBERG:  Absolutely, I agree with you.  And how did nurses help you manage your experience with your cancer treatment, as well as your husband's?  I mean, what was--and being a nurse, how did you relate to that and watch it happen?

MS. SACHSE:  Well, I think the biggest think that the nurses did, and I find the--really, a very important role is the anticipatory guidance to really know the treatments, know the drugs, and to really be able to say, these are the potential things that can happen, and like I said, and if it's written down, then I'd go to my book and say, hey, we're having this, this is a side effect, and this is okay. 

One of the practices that we dealt with had a call-in line, so that between visits, if we were having an issue, we could call in and talk to a nurse directly, and that was nice, because then we didn't have to go through a lot of different people and a lot of different steps, but I will have to say that as far as managing side effects, one of the biggest things that--it was like a light bulb went off for my husband, when he was referred to palliative care, and they were just rock stars as far as managing his pain, his nausea, you know, his loss of appetite, and I just can't say enough about palliative care and partnering with them to really help to mitigate these side effects for patients.

DR. ROSENBERG:  Yeah, and not only do they help with side effects in an enormous way, there are actually studies that have shown that simply by seeing palliative care in addition to your oncologist, you actually live longer than if you just--your oncologist, and if it was that fancy, expensive new drug, we'd be all over it, and everyone would get it, but because it's palliative care, people have an idea that, oh, why do I need these people, you know, but it really makes a huge difference for many patients, and one of the things that I feel lucky with is that we have palliative care within our own practice, actually.  We are co-located with a palliative care physician and team who are very accessible with us, at least before Covid, and I'm sure they'll be back once Covid is under control, but it really--I can't say enough about how helpful they can be, and it's a working partnership between the oncology team and the palliative care team, because they can focus on a lot of things while the oncologists, and the oncology team focuses on the cancer, it's really very helpful as a relationship.

So, one other thing we wanted to talk about specifically was clinical trials, because every treatment that every cancer patient gets these days, used to be in a clinical trial before it became a standard, accepted cancer treatment.  It's the only way that patients--that new treatments end up getting to be approved for patients for use widely.  The goal is not the trial, the goal is to develop better therapies, so that we treat our patients better, that people live longer and live better.

I just want to make one point, actually, that by the way, going back to what you were saying about palliative care, I think some patients think about palliative care as hospice care, and it's not--palliative care and hospice care are not the same thing.  Hospice care is end of life care, when cancer treatment is no longer an option, whereas palliative care is really symptom management.  In fact, at MSK, we've actually--they've changed the name of the service to the symptom management service, because there was this negative connotation which really shouldn't be there about palliative care, and so I just want to make that clear to people.  It may be a little confusing sometimes.

But going back to clinical trials, this has been a time of enormous change in the treatment of advanced bladder cancer.  I've been practicing since a little after 2000, and for about the first 15 years, 14 years of my practice, there wasn't really anything new.  We did a lot of clinical trials, nothing really worked, and it really felt like you were banging your head against the wall for a long time, and there has been an explosion of opportunities and options stemming from the understanding of the biology of bladder cancer, as well as work that has frankly been done on other diseases that got translated to bladder cancer and helped bladder cancer therapy, so the immunotherapy revolution, these antibody drug conjugates, all these types of treatments didn't start necessarily on bladder cancer, but we've learned very quickly from our colleagues, and we've been able to show that a lot of these treatments are very helpful.

There are a few things that are very exciting.  There are some novel immunotherapy approaches that are being tested in large clinical trials, and we may see some results from some of these in the next few years, where we're trying to target the immune system from different approaches.  Sometimes, it increases the side effects, but it also seems to increase the good effects, at least we think so, and so that's why some of those trials are very exciting, and these are things like targeting a molecule called CTLA4, autoimmune cells, in addition to targeting PD-1 or PDL-1, so combination immunotherapy, and there are some clinical trials now looking at combinations of targeted therapies and immunotherapies, with the idea that the targeted therapy might change the immune environment within the tumor, so that the immune system can actually better attack the cancer cells, and then there are trials now testing that drug, enfortumab vedotin, in combination with immunotherapy, and preliminary data has been very, very promising, and there are large, randomized trials going on now, trying to see if it's better than the regular chemotherapy that we give, and actually, the combination of enfortumab vedotin and pembrolizumab, which is one of those checkpoint drugs, immune drugs, was named as an FDA breakthrough therapy recently, and is in clinical trials in patients who have not had prior chemotherapy.

So, it's very important to think about clinical trials.  They're not always right for everybody, but it certainly should be on the list of options for patients.  Not every patient can get onto one because of their health issues sometimes, and not every patient feels like it's the right option for them, and that's totally fine.  How do you help patients wrap their heads around a clinical trial, Asia?  I mean, the first question that someone says to me is, oh, I don't want to go in a clinical trial because I don't want to get a placebo, well, and we have to explain to them that not all trials have placebos, and that most trials don't, so how do you break things down for patients so that they're aware of what's going on?  Because implication is critical.

MS. MCCOY:  Well, what I like to do initially is assess where they are knowledge-wise.  Nowadays, our patients are very intelligent, very savvy, they have a lot of information, and they know how to get a lot of information, so it's kind of helpful to figure out where to start, by figuring out what they already know.  Also, the myths about clinical trials, and kind of dispelling a lot of that stuff, you know, some patients will use terms as, you know, you just want me to be a guinea pig, or like, I'm a lab rat, or you have to encourage them and make them feel confident about the process of being a patient on a clinical trial.

Also, informing them about their rights and responsibilities as a clinical trial patient.  Once you sign your name on an informed consent, which is a legal document that authorizes us to screen a patient for a clinical trial, and also says, the patient, from a legal standpoint, has the understanding of the clinical trial that they may become a part of.  We can really get to the heart of the matter once we get some of those things out of the way.  So yeah, trying to help the patient in the most practical way that we can to peel back the layers, so that they have an understanding, because the fact is, it means nothing if they don't understand what's happening and what's going on with the clinical trial.  You don't want somebody on a trial who feels like they have no understanding of anything that's happening once they start to receive treatment.

DR. ROSENBERG:  So one of the--the informed consent process really has to be informed as much as possible, people have to understand what's going on, even--everyone, you have to meet people where they are, but they have to end up at least understanding what's part of this, what's part of the trial and what's not, and I always tell patients that I have a responsibility to the study, but my first responsibility is to you, the patient, in that we're going to look out for your interests first, but we also have to make sure that we're not violating the protocol, and doing things that we're not allowed to do and not supposed to do.

Videos

Webinar: Advanced Bladder Cancer

The FDA has approved the FoundationOne Liquid CDx for use as a companion diagnostic with olaparib (Lynparza), which is indicated for select patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene—mutated metastatic castration-resistant prostate cancer (mCRPC).

The diagnostic will utilize a blood-based biopsy to identify patients with mCRPC who harbor BRCA1, BRCA2, and/or ATM alterations who may be appropriate candidates for treatment with the PARP inhibitor.

“With this latest companion diagnostic approval, physicians now have the option to choose either tissue or liquid-based comprehensive genomic testing based on their patients’ need and condition. Since tissue availability can be an issue for some [patients with] metastatic prostate cancer, blood-based testing is an important option to consider and critically important for informing patient care,” Brian Alexander, MD, MPH, chief medical officer at Foundation Medicine, stated in a press release.

Previously, in August 2020, the FoundationOne Liquid CDx was approved by the FDA for all solid tumors with multiple diagnostic indications.

 The decision was based on analytical and clinical validation trials that collected more than 7500 samples and 30,000 unique variants across over 30 tumor types. When the platform was evaluated across these various tumors, the test demonstrated high sensitivity and specificity, even at the low allele frequencies that were observed in the blood samples that had been collected.

FoundationOne Liquid CDx is a tool that was developed to inform treatment decisions in accordance with FDA-approved labeling and professional guidance for patients with solid tumors. The assay is indicated for use as a companion diagnostic to identify which patients are appropriate for FDA-approved targeted therapies, such as rucaparib (Rubraca), which was recently FDA approved for select adult patients with mCRPC harboring a BRCA1/2 mutation, and 3 frontline TKIs in non—small cell lung cancer (NSCLC).

In October 2020, the FDA approved the FoundationOne Liquid CDx assay for use as a companion diagnostic for 3 targeted therapies in several tumor types: alpelisib (Piqray) in advanced or metastatic breast cancer, rucaparib in advanced ovarian cancer, and alectinib (Alcensa) in a specific type of NSCLC. The regulatory agency also allowed for a label expansion for the test to report additional select copy number alterations and genome rearrangements.

In May 2020, olaparib received regulatory approval for patients with deleterious or suspected deleterious germline or somatic HRR gene—mutated mCRPC who have progressed on previous treatment with either enzalutamide (Xtandi) or abiraterone acetate (Zytiga) based on data from the phase 3 PROfound trial.

Data from the trial demonstrated that treatment with olaparib reduced the risk of disease progression or death by 66% compared with abiraterone acetate or enzalutamide (hazard ratio [HR], 0.34; 95% CI, 0.25-0.47; P <.0001) in patients with BRCA1/2- or ATM-mutated mCRPC. In the entire population of patients with mCRPC who had mutations in genes for BRCA1/2, ATM, CDK12, or 11 other HRR-mutated genes, the PARP inhibitor resulted in a 51% reduction in the risk of disease progression or death versus either of the antiandrogen agents (HR, 0.49; 95% CI, 0.38-0.63; P <.0001).

The PARP inhibitor was also found to result in a statistically significant improvement in overall survival (OS) in patients with mCRPC who harbored BRCA1/2 or ATM mutations. In this subset, the median OS with olaparib was 19.1 months versus 14.7 months with enzalutamide or abiraterone (HR, 0.69; 95% CI, 0.50-0.97; P =.0175).

Cohort A of the trial comprised patients with alterations either in BRCA1/2 or ATM (n = 245), while cohort B included patients with other HRR gene mutations, such as BARD1, BRIP1, CDK12, CHEK1/2, FANCL, PALB2, PPP2R2A, RAD51B/C/D, or RAD54L. Patients were randomized 2:1 to receive either olaparib or physician’s choice of abiraterone plus prednisone or enzalutamide.

Additional results showed that the confirmed overall response rate (ORR) with olaparib in cohort A was 33.3% versus 2.3% with the antiandrogen agents (odd ratio [OR], 20.86; 95% CI, 4.18-379.18; P <.0001).

Moreover, the median time to progression had not yet been reached with the PARP inhibitor versus 9.92 months with the antiandrogen agents, translating to a 56% reduction in the risk of pain progression (HR, 0.44; 95% CI, 0.22-0.91; P =.0192). In this cohort, the median radiographic progression-free survival (rPFS) was 7.4 months with olaparib versus 3.6 months with hormonal therapy. In cohort B, the HR for rPFS was 0.88 by blinded review (95% CI, 0.58-1.36).

In both cohorts A and B, the median rPFS was 5.8 months with the PARP inhibitor versus 3.5 months with the antiandrogen agents. Additionally, in the combined cohorts, the ORRs with olaparib and the antiandrogen agents were 21.7% and 4.5%, respectively (OR, 5.93; 95% CI, 2.01-25.40; P =.0006). The median OS was 17.5 months and 14.3 months with olaparib and the hormonal agents, respectively (HR, 0.67; 95% CI, 0.49-0.9; P =.0063).

In May 2020, the tissue-based comprehensive genomic profiling test, FoundationOne CDx, was approved for use as a companion diagnostic for olaparib, according to Foundation Medicine, Inc.

“[Today’s] approval of this companion diagnostic will allow more patients to access genomic testing, regardless of specimen type, and provide oncologists with another tool to guide personalized treatment decisions,” added Alexander in the release.

1. Foundation Medicine expands indication for FoundationOne Liquid CDx to be used as a companion diagnostic for LYNPARZA. News release. Foundation Medicine, Inc. November 9, 2020. Accessed November 9, 2020. https://bit.ly/32oFxfi.

2. Lynparza approved in the US for HRR gene-mutated metastatic castration-resistant prostate cancer. News release. AstraZeneca. May 20, 2020. Accessed November 9, 2020. https://bit.ly/36eCJlP.

3. FDA approves FoundationOne Liquid CDx to serve as Rubraca (rucaparib) companion diagnostic to identify eligible patients with BRCA1/2-mutant, metastatic castration-resistant prostate cancer (mCRPC). News release. Clovis Oncology, Inc. August 26, 2020. Accessed November 9, 2020. https://bwnews.pr/2EEVIMm.

4. FDA approves Foundation Medicine’s FoundationOne Liquid CDx, a comprehensive pan-tumor liquid biopsy test with multiple companion diagnostic indications for patients with advanced cancer. News release. Foundation Medicine, Inc. August 26, 2020. Accessed November 9, 2020. https://bit.ly/2EtxNQs.

This article was originally published on OncLive as, "

FDA Approves FoundationOne Liquid CDx as Companion Diagnostic for Olaparib in Prostate Cancer.

The FDA has approved the FoundationOne Liquid CDx for use as a companion diagnostic with olaparib (Lynparza), which is indicated for select patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene–mutated metastatic castration-resistant prostate cancer (mCRPC).

FDA Approves Companion Diagnostic, FoundationOne Liquid CDx, for Olaparib in Prostate Cancer

The FDA has lifted the clinical hold placed on the phase 1 PSMA-101-001 study (NCT04249947) of the CAR T-cell therapy P-PSMA-101 in patients with metastatic castration-resistant prostate cancer (mCRPC), according to Poseida Therapeutics, Inc, the drug developer.

The company announced plans to resume the trial immediately, noting that they have agreed to make amendments to the protocol in an effort to increase patient compliance and safety. Some of these modifications are with regard to study inclusion and exclusion criteria, as well as frequency of monitoring and laboratory testing.

In August 2020, the regulatory agency made the decision to place a clinical hold on the trial examining P-PSMA-101 after a notification of a patient death had been issued by the company.

The patient, who had reportedly progressed on many anticancer agents prior to receiving the CAR T-cell therapy in late July 2020, had normal laboratory results after the first week of treatment; the patient did not showcase any clinical symptoms suggestive of an adverse effect, according to the company.

Despite this, the patient missed his follow-up visits that were scheduled for day 10 and day 14 following treatment with the product. During that time span, he reportedly presented with symptoms that resulted in hospitalization. On day 19, the patient experienced hepatic failure and died.

At the time of the report, the cause of the hepatic failure had not been confirmed, although the patient experienced symptoms that proved to be consistent with macrophage activation syndrome (MAS). It is known, however, that MAS can be caused by other events beyond treatment with CAR T-cell therapy, such as autoimmune disease or infection.

Moreover, the patient developed blurred vision and was diagnosed with uveitis, according to the company. The toxicity was determined to potentially be linked with P-PSMA-101 per investigator assessment, although the company announced that they would be looking into this further.

No other participants enrolled to the study experienced severe toxicities of reduced vision, uveitis, MAS, or hepatic failure. Moreover, no patients reported cytokine release syndrome or neurotoxicity with the product.

Designed to target prostate-specific membrane antigen, P-PSMA-101 was developed using Poseida’s piggyBac DNA Modification System, which produces agents with a high percentage of stem cell memory cells.3 These cells are able to reconstruct T-cell subsets, such as effecter T cells, which play a key role in eliminating cancer cells. Additionally, the higher composition of stem cell memory cells is hypothesized to be able to potentially overcome challenges associated with earlier-generation CAR T-cell therapies, according to the company.

The open-label, multicenter, dose-escalating phase 1 trial was designed to identify the optimal dose of the CAR T-cell product for safe administration in patients with mCRPC.

 Patients had to have metastatic disease that continued to grow despite prior treatment for advanced CRPC in order to participate. Moreover, they had to have recovered from any serious toxicities that occurred from previous treatment. If they had acceptable organ function with predetermined parameters and an ECOG performance status ranging from 0 to 1, they were eligible for inclusion.

However, if patients had unacceptable venous access and/or contraindications to leukapheresis or they had an active second malignancy beyond mCRPC, active autoimmune disease, a history of significant central nervous system disease, or an active systemic infection, they could not participate. If they had received anticancer medications within 2 weeks of conditioning chemotherapy, immunosuppressive treatment within 2 weeks of initiating leukapheresis, or systemic corticosteroid therapy in that time, they were not permitted.

The primary end point of the trial is safety, establishing the maximum-tolerated dose, and efficacy. In the trial, patients were given either single or multiple doses of P-PSMA-101; the first participant received treatment with the CAR T-cell product on May 20, 2020.

1. Poseida Therapeutics announces clinical hold lifted on phase I autologous CAR-T study in prostate cancer. News release. Poseida Therapeutics, Inc. November 2, 2020. Accessed November 2, 2020. https://prn.to/385OmOE.

2. Gergen MJ. Form 8-L: Poseida Therapeutics, Inc. United States Securities Exchange Commission. August 17, 2020. Accessed November 2, 2020. https://bit.ly/2CEl4cR.

3. Poseida Therapeutics announces dosing of first patient on phase 1 clinical trial of P-PSMA-01 autologous CAR-T for metastatic castration-resistant prostate cancer. News release. Poseida Therapeutics, Inc. May 20, 2020. Accessed November 2, 2020. https://bit.ly/3kQVjY5.

4. A phase I study of P-PSMA-01 CAR T-cell therapy in men with metastatic castration-resistant prostate cancer. Memorial Sloan Kettering Cancer Center. November 2, 2020. https://bit.ly/32iKLsn.

5. P-PSMA-01 CAR-T cells in the treatment of subjects with metastatic castration-resistant prostate cancer (mCRPC). ClinicalTrials.gov. Updated July 13, 2020. Accessed November 2, 2020. https://www.clinicaltrials.gov/ct2/show/NCT04249947.

FDA Lifts Hold on Phase 1 Trial of CAR T-Cell Therapy P-PSMA-101 in mCRPC

The FDA has lifted the clinical hold placed on the phase 1 PSMA-101-001 study (NCT04249947) of the CAR T-cell therapy P-PSMA-101 in patients with metastatic castration-resistant prostate cancer. 

FDA Lifts Hold on CAR T-Cell Trial for Prostate Cancer

A novel surgical technique called the “hood technique” for robotic-assisted radical prostatectomy was shown to achieve early return of urinary continence without a negative impact on complications and cancer outcomes among men with localized prostate cancer, according to study findings published in European Urology.

The findings indicate that the hood technique allows for early return of continence after surgery without compromising positive surgical margin rates by sparing musculofascial structures anterior to the urethral sphincter complex.

“A common [adverse] effect that patients worry about following a radical&#8239;prostatectomy is urinary incontinence,” said Ashutosh Tewari, MD, senior author of the trial.

 “This study shows that [by] using a novel surgical technique, the&#8239;robotic-assisted radical prostatectomy ‘hood technique,’ we can reduce postoperative urinary incontinence and facilitate early return of continence in patients with localized&#8239;prostate&#8239;cancer.”

The robotic-assisted radical prostatectomy hood technique is performed with the goal of preserving the detrusor apron, puboprostatic ligament complex, arcus tendinous, endopelvic fascia, and pouch of Douglas. Moreover, the technique preserves tissue after robotic-assisted radical prostatectomy by creating a “hood” to safeguard the membranous urethra, external sphincter, and supportive structures.

Currently, radical prostatectomy is the standard of care for patients with localized prostate cancer. However, despite improvements in surgical technique, patients may develop urinary incontinence as a result of surgery.

Identifying novel techniques to reduce the risk of urinary incontinence is key to improving patients’ quality of life, which can be significantly impacted as a result of radical prostatectomy.

The institutional review board—approved study enrolled 300 patients with localized prostate cancer who underwent robotic-assisted radical prostatectomy with the hood technique. Patients were accrued between April 2018 and March 2019 to Mount Sinai Health System, where the study was conducted. 

Patients with anterior tumor location based on biopsy or multiparametric MRI were excluded from the study.

Among all patients, the median age was 64 years. All but 1 patient participated in the 12-month follow-up following robotic-assisted radical prostatectomy with the hood technique.

Pre- and intraoperative variables, as well as postoperative functional and oncological outcomes and complications were collected as clinical data. Additionally, descriptive statistical analysis was performed.

At 1, 2, 4, 6, 12, 24, and 48 weeks after catheter removal, the continence rates among patients were 21%, 36%, 83%, 88%, 91%, 94%, and 95%, respectively. The positive surgical margin rate was 6%. 

A minority of patients (9.7%; n = 30) experienced complications after robotic-assisted radical prostatectomy, including Clavien-Dindo grade I (5.7%; n = 17), grade II (3.6%; n = 11), and grade III (0.4%; n = 1) complications. 

The hood technique might offer an alternative approach to the traditional robotic-assisted radical prostatectomy anterior approach.2 Moreover, the novel technique may confer early continence, low positive surgical margin rate, and the ability to visualize anatomical landmarks.2 

Regarding limitations, the study was conducted within a single institution, so therefore, the results may not be applicable to the general patient population. Additionally, the study was nonrandomized and lacked a comparative arm.

1. Wagaskar VG, Mittal A, Sobotka S, et al. Hood technique for robotic radical prostatectomy—preserving periurethral anatomical structures in the space of retzius and sparing the pouch of Douglas, enabling early return of continence without compromising surgical margin rates. Published online October 14, 2020. Accessed October 21, 2020. Eur Urol. doi:10.1016/j.eururo.2020.09.044

2. Mount Sinai study shows novel surgical technique for prostate cancer improves urinary continence. News release. Newswise. October 16, 2020. Accessed October 21, 2020. https://bit.ly/3m2pyuK

This article originally appeared on OncLive as, "

Alternative Surgical Technique Induces Early Return of Continence in Localized Prostate Cancer.

Robotic-assisted radical prostatectomy was shown to achieve early return of urinary continence without a negative impact on complications and cancer outcomes among men with localized prostate cancer.

New Prostate Cancer Surgical Technique Improves Continence

The FDA has granted a priority review designation to a supplemental biologics license application and supplemental new drug application for nivolumab (Opdivo) plus cabozantinib (Cabometyx) for the treatment of patients with advanced renal cell carcinoma, according to Bristol Myers Squibb and Exelixis, Inc.

The applications are based on data from the phase 3 CheckMate-9ER trial, which showed that the combination resulted in a 49% reduction in the risk of disease progression or death, significantly improved overall survival (OS), and doubled objective response rates (ORRs) versus sunitinib (Sutent) when used as a frontline treatment in patients with RCC.

Specifically, the median progression-free survival (PFS) was 16.6 months with nivolumab plus cabozantinib versus 8.3 months with sunitinib at a median follow-up of 18.1 months (HR, 0.51; P <.0001). The combination also demonstrated a tolerable toxicity profile, with a low rate of drug-related discontinuations in patients with advanced disease.

Under the Prescription Drug User Fee Act, the FDA must make a decision on the applications by February 20, 2021.

“We have witnessed practice-changing advancements in the treatment of RCC in recent years, but we recognize the importance of providing patients and physicians with additional options that can help them take control of the disease,” said Mark Rutstein, vice president and development program lead of Opdivo at Bristol Myers Squibb.1 “In the CheckMate-9ER, combining [nivolumab] and [cabozantinib], 2 proven agents with strong clinical legacies in advanced RCC, led to superior efficacy across all end points. We look forward to working with the FDA to bring this potential treatment option to physicians and their patients who choose an immunotherapy plus TKI regimen.”

In the international phase 3 trial, a total of 651 patients with advanced RCC were randomized to receive either nivolumab/cabozantinib (n = 323) or sunitinib (n = 328) as frontline treatment. To be eligible for participation, they had to have treatment-naïve advanced or metastatic disease, a clear cell component, and any International Metastatic RCC Database Consortium (IMDC) risk score.

Participants were randomized in a 1:1 fashion. Those in the combination arm received intravenous nivolumab at 240 mg every 2 weeks in combination with oral cabozantinib at a daily dose of 40 mg. In the control arm, patients were given oral sunitinib at a daily dose of 50 mg on a 4-weeks-on/2-weeks-off cycle. Patients received treatment until progressive disease or intolerable toxicity.

The primary end point of the trial was PFS, and key secondary end points included OS, ORR, and safety. An exploratory end point of CheckMate-9ER was health-related quality of life (HRQoL).

Results from CheckMate-9ER presented during the 2020 ESMO Virtual Congress showed that the combination proved beneficial across several subgroups analyzed, including age, sex, PD-L1 expression, bone metastases, IMDC risk group, and geographic region.

The median OS had not yet been reached in either treatment arm, translating to a 40% reduction in the risk of death with nivolumab/cabozantinib (HR, 0.60; P = .0010).

Moreover, the ORR with nivolumab/cabozantinib in this setting was 55.7% versus 27.1% with sunitinib (P <.0001). In the investigational arm, the complete response (CR) rate was 8.0%, the partial response (PR) rate was 47.7%, and the stable disease (SD) rate was 32.2%. Also, 5.6% of patients experienced disease progression, while 6.5% were not evaluable or not assessed. In the control arm, the CR, PR, and SD rates were 4.6%, 22.6%, and 42.1%, respectively. Additionally, 13.7% experienced progressive disease and 17.1% were not evaluable or not assessed.

With regard to safety, any-grade and high-grade treatment-related adverse effects (TRAEs) proved to be comparable between the 2 arms. More than half of the participants on the combination arm needed dose reductions of cabozantinib because of toxicities. Additionally, 15.3% of those who received the combination experienced TRAEs that led to treatment discontinuation; 8.8% of those who received sunitinib discontinued treatment due to TRAEs.

Moreover, 3.1% of participants discontinued both nivolumab and cabozantinib because of toxicities, 5.6% discontinued nivolumab only, and 6.6% discontinued cabozantinib only.

The rate of serious toxicities was also comparable between the 2 arms, although liver toxicity was found to be more frequently reported with the combination. Nineteen percent of participants on nivolumab/cabozantinib needed treatment with corticosteroids because of immune-associated AEs; of these patients, 4% required corticosteroids for at least 30 days.

Additionally, nivolumab/cabozantinib was found to improve HRQoL versus sunitinib. HRQoL was maintained over time with the combination compared with sunitinib, which had a consistent deterioration per Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI)-19 total score. The between-arm differences were found to be significant at almost all time points.

The combination also improved disease-related symptoms (DRS), while those who were given sunitinib experienced a decline per FKSI-Disease-DRS.

“With their complementary mechanisms of action and evidence that [cabozantinib] may promote a more immune-permissive environment, we believe there is opportunity for additive or synergistic effects with this potential combination regimen,” said Gisela Schwab, MD, president of product development and medical affairs and chief medical officer of Exelixis.1 “Based on strong supporting data from CheckMate-9ER, the acceptance of our application is important progress in our efforts to make [cabozantinib] in combination with [nivolumab] available to patients with advanced kidney cancer who need additional treatment options. We look forward to working with the FDA throughout the ongoing review process.

Nivolumab and cabozantinib are currently approved in separate indications in RCC. In April 2018, the FDA gave the green light to nivolumab/ipilimumab (Yervoy) as a first-line treatment for intermediate- and poor-risk patients with advanced RCC. Prior to that, in 2015, the PD-1 inhibitor received regulatory approval for use as a monotherapy in the treatment of patients with metastatic RCC after previous antiangiogenic therapy.

In 2017, cabozantinib received approval by the FDA for the treatment of treatment-naïve patients with advanced RCC; the agent was initially approved for use in those who had progressed on 1 prior antiangiogenic treatment.

1. US Food and Drug Administration accepts for priority review applications for Opdivo (nivolumab) in combination with Cabometyx (cabozantinib) in advanced renal cell carcinoma. News release. Bristol Myers Squibb and Exelixis, Inc. October 19, 2020. Accessed October 19, 2020. https://bit.ly/3o5OvY9&#8203;

2. Choueiri TK, Powles T, Burotto M, et al. Nivolumab + cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: first results from the randomized phase 3 CheckMate 9ER trial. Ann Oncol. 2020;31(4). Abstract 696O.

FDA Grants Priority Review to Nivolumab Plus Cabozantinib in Advanced RCC.

The FDA has granted a priority review designation to a supplemental biologics license application and supplemental new drug application for nivolumab (Opdivo) plus cabozantinib (Cabometyx) for the treatment of patients with advanced renal cell carcinoma. 

Nivolumab Plus Cabozantinib Gets Priority Review for Advanced RCC Treatment

A new drug application (NDA) has been submitted to the FDA for TLX591-CDx (illumet), a radiopharmaceutical product that targets prostate-specific membrane antigen (PSMA), for the imaging of prostate cancer through the use of positron emission tomography, according to an announcement from Telix Pharmaceuticals Limited.1

The application for the product is comprised of clinical findings collected from over 600 patients who participated in prospective and retrospective clinical trials that were conducted by Telix Pharmaceuticals or in collaboration. The NDA is also based on definitive peer-reviewed clinical research that had been conducted at the University of California, Los Angeles (UCLA), the Peter MacCallum Cancer Centre, and Heidelberg University Hospital.

“We are pleased to have achieved this significant milestone with the submission of the first commercial NDA for PSMA imaging in the United States,” Bernard Lambert, MD, president of Telix Pharmaceuticals USA, stated in a press release. “Telix has engaged with the FDA since July 2019, with valuable guidance resulting in what we believe to be a comprehensive submission. Subject to FDA approval, we look forward to bringing this product to market with our commercial partners to serve the needs of men living with prostate cancer.”

TLX591-CDx is a radiopharmaceutical for the imaging of metastatic prostate cancer. The imaging product comes in a “cold kit” to allow for quick preparation of 68Ga-PSMA-11 injection, rapid radiolabeling at room temperature with high radiochemical purity; it is compatible with the 68Ga generators that are already commercially available.2

The product is being used in research efforts under investigational new drug applications at Emory University Hospital, Memorial Sloan Kettering Cancer Center, and Endocyte.

The pharmaceutical company has also partnered with Cardinal Health, UPPI, and Pharmacologic in the United States for pharmacy preparation purposes, as well as to distribute the kit as an investigational product for use in investigator-sponsored research efforts.

Imaging with 68Ga-PSMA-11 PET has been shown to result in significant changes in the management of biochemically recurrent prostate cancer. In a prospective, single-arm trial, referring physicians applied 68Ga-PSMA-11 PET&shy;—based recommended management changes to 72% (n = 98) of 136 patients.3 68Ga-PSMA-11 PET resulted in the prevention of unnecessary diagnostic tests and a reduction in the proportion of patients with unknown sites of disease.

The study had included participants with prostate adenocarcinoma and biochemical recurrence. These patients were recruited at UCLA and the University of California, San Francisco.

A new drug application has been submitted to the FDA for TLX591-CDx, a radiopharmaceutical product that targets prostate-specific membrane antigen, for the imaging of prostate cancer through the use of positron emission tomography.

Genitourinary Cancer