The FDA has granted priority review to the new drug application for the HIF-2α inhibitor belzutifan (MK-6482) for the potential treatment of patients with von Hippel-Lindau (VHL)–associated renal cell carcinoma (RCC) that does not require immediate surgery.

The application was based on findings from the phase 2 Study-004 trial (NCT03401788), in which the agent demonstrated a confirmed overall response rate (ORR) of 36.1% (n = 22/61; 95% CI, 24.2%-49.4%) in this patient population.

Under the Prescription Drug User Fee Act, the FDA is slated to make a decision on the application by September 15, 2021.

“VHL disease is a rare genetic condition for which there is no systemic treatment option available and is associated with a high risk of cancer development in multiple organs. In fact, up to 70% of patients with VHL develop RCC during their lifetime,” Scot W. Ebbinghaus, MD, vice president of clinical research at Merck Research Laboratories, stated in a press release. “This priority review validates the important progress we have made to expand and diversify Merck’s oncology pipeline with innovative, new therapeutic approaches. We look forward to working closely with the FDA to bring belzutifan to patients in need.”

A rare autosomal dominant hereditary disorder caused by germline pathogenic variants of the 

 gene, VHL disease is linked with benign and malignant tumors such as clear cell RCC, pancreatic neuroendocrine tumors, central nervous system (CNS) hemangioblastomas, and retinal lesions.

 The majority, or 70%, of those with this disease will go on to develop clear cell RCC.

Belzutifan is a potent, selective, small molecule HIF-2α inhibitor showcased antitumor activity with an acceptable toxicity profile when utilized in patients with advanced clear cell RCC in a phase 1 trial.3 Here, after a median follow-up of 27.7 months, belzutifan induced an ORR of 25% (95% CI, 15%-39%) in patients with heavily pretreated, advanced clear cell RCC. 

In the open-label, single-arm phase 2 trial, investigators set out to examine belzutifan as a potential option for patients with VHL disease–associated RCC. To be eligible for enrollment, patients had to have at least 1 measurable tumor and an ECOG performance status of 0 or 1. Patients could not have previously received systemic therapy, nor could they have metastatic disease.

A total of 61 patients were enrolled to the trial. Participants received oral belzutifan at a once-daily dose of 120 mg until either progressive disease or intolerable toxicity. The primary end point of the trial was ORR in this patient population per RECIST v1.1 criteria and independent review committee. Key secondary end points included disease control rate, duration of response, duration of response (DOR), time to response (TTR), progression-free survival (PFS), time to surgery, and safety in RCC tumors.

The median age of study participants was 41 years, 52.5% were male, and the majority (82.0%) had an ECOG performance status of 0. The median number of prior surgeries received per patient was 4. All patients had pancreatic lesions, 82.0% had CNS hemangioblastoma, and 26.2% had retinal lesions.

Additional results from the trial presented during the 

 showed that 36.1% of patients experienced a partial response to belzutifan, 62.3% had stable disease, and 1.6% of patients were not evaluable. The median TTR was 31.1 weeks (range, 11.6-61.0) and. the median DOR had not yet been reached (range, 11.9-62.3).

The PFS rate with the agent at 52 weeks was 98.3%.

Moreover, 91.8% of patients (n = 56/61) experienced a reduction in the size of their target clear cell RCC lesions with the HIF-2α inhibitor.

Regarding safety, all patients experienced any-grade toxicities, while 98.4% experienced any-grade toxicities that were related to treatment. Additionally, 24.6% experienced toxicities that were grades 3 to 5 in severity, while 13.1% had grade 3 toxicities that were treatment related. Approximately 3% of patients experienced a toxicity that resulted in treatment discontinuation, 1.6% of which were determined to be related to the therapy. One patient died, but the death was not determined to be associated with the treatment.

The most frequently reported toxicities of any grade included anemia (90.2%), fatigue (60.7%), headache (37.7%), dizziness (36.1%), nausea (31.1%), dyspnea (19.7%), arthralgia (18.0%), upper respiratory tract infection (18.0%), increased alanine aminotransferase level (16.4%), and myalgia (16.4%). Grade 3 effects included anemia (6.6%), fatigue (4.9%), and dyspnea (1.6%). No grade 4 or 5 effects were reported.

The agent is also under exploration in phase 3 trials as a single agent and as part of a combination in previously treated patients, as well as in a combination being examined in the frontline treatment of patients with advanced clear cell RCC.

FDA granted a breakthrough therapy designation to belzutifan

 for the treatment of patients with VHL disease–associated RCC who have nonmetastatic tumors of less than 3 centimeters, unless immediate surgery is required.

Merck receives priority review from FDA for new drug application for HIF-2α inhibitor belzutifan (MK-6482). News release. Merck. March 16, 2021. Accessed March 16, 2021. 

Iliopoulos O, Jonasch E, Donskov F, et al. Phase II study of oral hypoxia-inducible factor 2α inhibitor MK-6482 for Von Hippel-Lindau (VHL) disease-associated clear cell renal cell carcinoma (ccRCC). 

. 2021;39(suppl 6):333. doi:10.1200/JCO.2021.39.6)suppl.333

Bauer TM, Choueiri TK, Papadopoulos KP, et al. The oral HIF-2 α inhibitor MK-6482 in patients with advanced clear cell renal cell carcinoma (RCC): updated follow-up of a phase I/II study. 

. 2021;39(suppl 6):273. doi:10.1200/JCO.2021.39.6_suppl.273

This article was originally published on OncLive as, "

FDA Grants Priority Review to Belzutifan for VHL Disease–Associated RCC

Articles

The FDA has granted priority review to the new drug application for the HIF-2α inhibitor belzutifan for the potential treatment of patients with von Hippel-Lindau–associated renal cell carcinoma that does not require immediate surgery.

Belzutifan Granted Priority Review for VHL Disease–Associated RCC

The FDA has approved tivozanib (Fotivda) for the treatment of adult patients with relapsed/refractory advanced renal cell carcinoma (RCC) following 2 or more prior systemic therapies.1

The approval is primarily based on findings from the phase 3 TIVO-3 trial, in which tivozanib demonstrated a significant improvement in progression-free survival (PFS) compared with sorafenib (Nexavar), with similar overall survival (OS), in patients with highly relapsed/refractory metastatic RCC.2

“Today’s approval of Fotivda provides a new tool for treating patients with kidney cancer who have relapsed or become refractory to 2 or more prior systemic therapies,” said lead study author Brian Rini, MD, chief of Clinical Trials at Vanderbilt Ingram Cancer Center. “With advances in RCC treatment, patients are living longer, increasing the need for proven, well-tolerated treatment options in the relapsed or refractory setting. The TIVO-3 study is the first positive phase 3 study in RCC patients who received 2 or more prior systemic therapies, and also the first phase 3 RCC study to include a predefined population of patients who have received prior immunotherapy, the current standard of care in earlier-line treatment. With this approval, I believe Fotivda represents an attractive intervention, and expect it to play a meaningful role in the evolving RCC treatment landscape.”

Data showed that the final hazard ratio (HR) for OS was 0.97 (95% CI, 0.75-1.24; 

 = .78). Moreover, an updated analysis of the data found that, with a median follow-up of 38 months for tivozanib and 40 months for sorafenib, the median OS was 16.4 months for tivozanib (95% CI, 13.4-22.2) and 19.2 months for sorafenib (95% CI, 15.0-24.2). A subset analysis showed the greatest benefit was derived by the cohort of patients who previously received a checkpoint inhibitor and VEGF inhibitor, with an HR of 0.55, or 2 VEGF TKIs, with an HR of 0.57.

Prior findings showed an increased median PFS for tivozanib when compared with sorafenib at 5.6 months versus 3.9 months, respectively (HR, 0.73; 95% CI, 0.56-0.94; 

The TIVO-3 study was a controlled, multicenter, open-label, phase III trial which randomized 350 patients with highly refractory metastatic RCC who had failed ≥2 prior regimens, including VEGF-TKI treatment, 1:1 to receive either oral tivozanib or sorafenib. Crossover between arms was not permitted.

Eighteen percent (n = 31) of patients in the tivozanib arm achieved partial response, compared with 8% (n = 14) of those in the sorafenib arm. The objective response rate was 34% for tivozanib versus 24% for sorafenib.

Treatment with tivozanib was found to be generally well-tolerated, and the safety profile was favorable when compared with sorafenib. Treatment-related adverse events (TRAEs) were reported in 84% (n = 146) of patients receiving tivozanib and 94% (n = 160) of those receiving sorafenib. Serious TRAEs occurred in 11% (n = 19) of patients treated with tivozanib versus 10% (n = 17) of patients who received sorafenib.

The most common grade 3 or 4 AE reported in patients receiving tivozanib and sorafenib was hypertension (21% vs 14%, respectively). The most commonly reported any grade AEs associated with tivozanib were hypertension (38%), diarrhea (33%), fatigue (29%), and decreased appetite (27%).

The investigators reported significantly reduced dose reductions and interruptions due to AEs for tivozanib versus sorafenib (48% vs 63%; 

 = .0164), despite nearly double the average time of cycles initiated for the tivozanib arm (11.9 months vs 6.7 months, respectively). Treatment related AEs leading to permanent discontinuation were 8% for tivozanib compared with 15% for sorafenib.

“We believe in Fotivda's potential to provide a differentiated treatment option for the growing number of individuals in the [United States] with relapsed or refractory RCC, and today marks the culmination of many years of hard work and determination of many individuals to bring this therapy to patients,” said Michael Bailey, president and chief executive officer of AVEO Oncology. “With today’s approval, AVEO begins its journey as a commercial-stage company, a noteworthy accomplishment in our industry. On behalf of the entire AVEO team, I would like to thank all the patients, their families, and caregivers whose tireless efforts made this day possible.”

AVEO Oncology Announces U.S. FDA Approval of FOTIVDA® (tivozanib) for the Treatment of Adult Patients with Relapsed or Refractory Advanced Renal Cell Carcinoma. AVEO Oncology. News release. March 10, 2021. Accessed March 10, 2021. https://bwnews.pr/3byYtgo

Pal SK, Escudier B, Atkins MB, et al. TIVO-3: Final OS analysis of a phase III, randomized, controlled, multicenter, open-label study to compare tivozanib to sorafenib in subjects with metastatic renal cell carcinoma (RCC). Presented at: 2020 ASCO Virtual Program; May 27, 2020. Abstract 5062.

FDA Approves Tivozanib for Relapsed/Refractory Advanced RCC

Advanced practice providers are essential in treating patients with genitourinary cancers, especially as there is a shortage of clinicians in this space. 

Meredith E. Donahue, APRN-BC, shares how her career path brought her to urology, the numerous ways she supports a urology department, and how others may pursue a similar professional focus. Donahue is an advanced practice registered nurse in the Department of Urology at Vanderbilt University, Nashville, Tennessee. She was interviewed by 

™ Editor-in-Chief Raoul S. Concepcion, MD, FACS, director of the Comprehensive Prostate Center and clinical associate professor of urology at Vanderbilt University School of Medicine.

Please explain how you ended up in urology. Did you receive specialized training after obtaining your master of science in nursing?

After graduating from Furman University [in Greenville, South Carolina], with a bachelor’s in science, I was open to any job options when I landed at Urology Associates in Nashville, Tennessee. After my initial exposure to urology, I realized this is where I wanted to spend the rest of my career practicing.

When I started my master’s, I tried my best to experience every part of medicine but ultimately found myself coming back to urology, and specifically urologic oncology. When it came time to figure out next steps and what to do with a master’s, it was obvious that a urology nurse practitioner (NP) fellowship was the best next step for me. Fortunately, I was accepted to Vanderbilt University Medical Center’s Department of Urology NP Fellowship, where I was able to receive a year of specialized training in urology.

There are multiple ways to become an APP. For NPs, one must have a bachelor’s in nursing or any bachelor of science [degree], a registered nurse license, and complete a master of science in nursing. … For physician assistants (PAs), one completes a bachelor’s degree in any field and then completes a master’s program. Both tracks prepare students to [work with] patients as generalists but offer little to no specialty training unless sought out by the student. Thus, making the transition into a specialty like urology may be quite difficult.

That’s where APP fellowships have proved to be pivotal in training APPs in specialty practice to be confident and independent providers. There are only a handful of urology APP fellowships across the country, so it is not reasonable to think all APPs can be trained in that way. It is important to provide adequate onboarding and education for APPs starting a new position in a specialty. With that said, it is exciting to be a part of this growing field of urology APP fellowships.

My now-colleague Gilbert Comola [ANP, CURN], who also completed an APP fellowship in urology, is the director of the fellowship and worked with the Office of Advanced Practice to develop a comprehensive training program in urology that includes spending time with each subspecialty of urology in the outpatient setting and in the operating room, as well as providing inpatient care to primary urology patients and consults. In the fellowship, I was also given dedicated time with our physicians to learn how to perform cystoscopies. With this skill, I can perform hematuria evaluations and stent pulls, or [can] address acute concerns that may require Foley [catheter] placement under cystoscopic guidance. In the fellowship, I had required didactic work as well as attendance at weekly conferences and lectures. This correlated with what I was learning clinically and has ultimately kept me eager to continue attending these educational opportunities beyond the fellowship.

What is your current position in the Department of Urology at the Vanderbilt University School of Medicine?

I am a nurse practitioner in the department of urology and more specifically with our oncology team. I primarily support Joseph Smith, MD, and David Penson, MD. I have my own template every day, but when Dr Smith and Dr Penson are in clinic, I help support them by seeing patients and obtaining new patient histories, and by keeping the patient flow moving. I am also fortunate to share patients with all our urologic oncology [physicians]: Sam Chang, MD; Amy Luckenbaugh, MD; Dan Barocas, MD; and Kelvin Moses, MD. I am lucky to work with all these physicians because I can continue to learn from each of them in different ways.

My current position is all outpatient, working 5 days a week with 1 administrative day. Typically, I spend this time catching up on notes, fielding the urgent/emergent calls for my patients and my MDs, following up on results, and performing peer-to-peer consults. At this point, APPs in our clinic do not take any call.

What are your daily clinical responsibilities as they relate to patients with genitourinary (GU) cancer?

Most of my days are seeing new, return, and postoperative patients. These visits are interspersed along with following up on labs, imaging, and managing urgent and emergent calls from my patients and the patients of the physicians I primarily work with. I also spend half a day seeing patients in our advanced prostate cancer clinic with Dr Moses as well as half a day running our BCG clinic, instilling different intravesical therapies. All these roles certainly keep me busy and challenge me every day.

What challenges has the coronavirus disease 2019 (COVID-19) pandemic lockdown created in helping your patients with cancer, and how have you overcome these?

At the start of the pandemic, the most difficult part was patients asking us whether they were at higher risk by coming to Vanderbilt versus higher risk by delaying surveillance imaging, treatments, or addressing onset signs/symptoms. At the beginning, we didn’t have answers to these questions; I don’t think anyone did. Fortunately, our team quickly learned how to adjust and appropriately guide our patients to keep them safe during the pandemic but also safely and appropriately manage their GU malignancy. Of course, this wasn’t easy. This required our team and me to learn and stay up to date on all the ever-changing COVID-19 data.

You may not have asked, but for every challenge during this time, I like to find the silver linings. During this pandemic, I have found patients to be more open to discuss how they are feeling physically … emotionally and mentally about their health and diagnosis. In my (biased) opinion, [receiving a diagnosis of] a GU malignancy is one of the most vulnerable diagnoses a patient can encounter. It’s always a special moment when I see that wall come down, that wall of fear and embarrassment having to discuss not only a malignancy but also parts of their body they may have never talked about before. I think this pandemic has shown patients and even our society that it is OK to talk with health care providers about how you are feeling both physically and emotionally. It is exciting to see this shift and is a reminder that cancer is not just a diagnosis of their physical body but also of the patient’s mental and emotional health.

Can you think of situations in which, because of your training, APPs can be better utilized to enhance quality and efficiency of care for patients with GU cancer?

Although I am a GU oncology NP, there are numerous adverse events (AEs) from the management of these malignancies that require input from other disciplines of urology, including voiding dysfunction, sexual medicine, and endourology, requiring me to have knowledge in each of these areas. Having training in all of urology during my fellowship has given me the tools and confidence to manage these issues on my own and the understanding of when to refer for a higher level of care. For example, the most common AEs of radical prostatectomy are urinary incontinence and erectile dysfunction. The fellowship allowed me to learn from our experts in each of these areas to appropriately manage patients on my own and [to gain] an understanding of when to advance the level of care for possible surgical therapies. So I can confidently manage a postprostatectomy PSA [prostate-specific antigen] but also any other urologic concerns that arise post-therapy. Another benefit that I and one of my supervising physicians, Dr Smith, identified is that I am able to commit more time to management of these significant life-altering issues and formulate surveillance plans for our patients, ultimately allowing him more time for new patients, operating, or seeing our more complex patients.

Regarding managing postsurgical complications in this population, having spent time in the operating room as well as with our inpatient service has given me invaluable tools to acutely take care of patients in the possible urgent/emergent concerns in the postoperative period. It gave me awareness to know what I can manage in the outpatient versus when to admit someone for inpatient care.

Over the next 5 years, how do you think the role of the APP will evolve, given the advancement of diagnostic testing and plethora of new therapies (and indications) across the various tumor types?

It is certainly an exciting time, witnessing and being a part of the advancements in diagnostic tests as well as novel therapies in urologic oncology. APPs are and will continue to be critical in the implementation and education for patients during the advancement of new tests and therapies.

During the past few months, I have worked closely with our medical oncology team and the hereditary cancer clinic to bring germline testing into the urology clinic for [patients at high risk of prostate cancer who] qualify based on the latest NCCN [National Comprehensive Cancer Network] guidelines. As an APP, I have the time to both set up the logistics of having a new test to offer as well as the time to spend with patients educating them on germline testing in high-risk prostate cancer. There have certainly been logistic hurdles along the way with incorporating a new test into our flow of these, but I have been fortunate to work with a multidisciplinary team to make this process both easy to understand and streamlined for our patients. As we mature our process in offering genomic testing in the urology clinic, our hope is that this multidisciplinary approach can be adopted at other institutions nationwide. Across urologic oncology, there are new and developing testing and therapies, including prostate-specific membrane antigen scanning, blue light cystoscopy, and novel intravesical treatments. With these complex advances comes the increasing need for a team-based approach in the care of our patients. The APP plays a special role as a medical provider closely working with the physician in management, as the patient advocate, and as a liaison for the multidisciplinary approach that these advances will require us to take.

Of course, this will require APPs to stay prudent on learning these changes and updates. We have all our APPs join the American Urological Association, which has vast amounts of education, lectures, and of course guidelines. Likewise, we encourage having NCCN accounts as well as memberships in the Society of Urologic Nurses and Associates and other groups to keep ourselves educated on the quickly changing landscape of urologic oncology.

You are employed in a very highly specialized academic environment. What do you think would be the major critical pieces that independent urology groups should be considering in order to incorporate APPs into their advanced cancer care model?

APP utilization in urology is a topic that [many of my colleagues and I] are always working to improve and maximize. Before incorporating APPs into advanced cancer care, it is critical to start early with adequate education and training. As APPs, we are trained in primary care, where we learn how to medically manage patients. But making the transition to specialize and focus on a particular discipline can be a difficult task. That is where urology groups must take responsibility to provide adequate time and resources for newly hired APPs (those who did not complete a fellowship) to learn how to confidently manage the breadth of urology patients, and in this case urologic oncology patients. My APP colleagues and I have created a formal onboarding plan for newly hired APPs that requires more work on the front end but ultimately pays off when we have a new APP who can function independently.

Having worked in an independent urology group prior to becoming an NP, I have a good sense of the similarities and differences of independent groups versus academic urology. Regarding utilization of APPs, I don’t think our roles differ drastically. In independent urology groups, APPs likely work more as general providers [because] the physicians tend to see all areas of urology. If independent urology groups want to specialize their APPs into oncology roles, there are certainly efficient ways to do so.

Once you have an appropriately trained APP, the options for incorporating them into your advanced cancer care model are endless. An easy way to incorporate APPs into your model is to have the APP see the returns and [patients undergoing routine cancer surveillance]. This could be seeing patients for routine PSA monitoring or surveillance imaging and labs for patients with a history of urothelial carcinoma or renal neoplasms. This allows our MDs more time to see the new patients, the more complex patients, and even more time in the operating room. We even take advantage of this model in our advanced prostate cancer clinic. For example, patients [doing well on therapy whose PSA is stable], I can see … independently, draw labs, give any injections, address AEs/concerns, and send on their way, ultimately leaving Dr Moses more time with our new and more complex patients who often require extensive counseling and evaluation.

Again, in our model at Vanderbilt, our BCG/intravesical therapy clinic is managed by an APP. This includes not only giving patients their treatments but also managing adverse events, questions, and concerns from the patients. This is an excellent way to utilize APPs, because intravesical therapies often come with a host of AEs that must be medically managed. Likewise, having an APP run an intravesical therapy clinic gives patients another provider who understands their pathology, diagnosis, and scheduled treatment plan.

An nurse practitioner discusses how she supports multiple providers in a large academic practice.

APPs Are Key in GU Cancer Care

While second-generation androgen receptors such as apalutamide (Erleada) and enzalutamide (Xtandi) have improved outcomes for men with nonmetastatic castrate-resistant prostate cancer (nmCRPC), they can come with adverse events (AEs) that are often unresolved, according to recent research presented at the 2021 Genitourinary Cancers Symposium.

“The objective of the present study was to describe the patient characteristics, the frequency of a disease or adverse events amongst patients receiving apalutamide or enzalutamide [and] how these adverse events are managed in a real-world setting, and what is the health care resource utilization for these patients,” said study author Arif Hussain, MD, professor of medicine at the University of Maryland Medical System.

The researchers analyzed 368 patients with nmCRPC who were taking apalutamide and 333 on enzalutamide. In this group, 72% and 78.8% experienced 1 or more AE in the apalutamide and enzalutamide group, respectively. Hussain noted that they did not investigate outcomes for darolutamide (Nubeqa) because they did not have sufficient data on the drug at the time of the study.

The most common AEs in the apalutamide and enzalutamide groups were:

Fatigue/asthenia (30.2% vs 38.7%, respectively)

Notably, cognitive and mental changes were also observed in 5.4% of men on apalutamide and 7.8% of men on enzalutamide.

From the total group, the researchers further analyzed 125 patients on apalutamide and 125 patients on enzalutamide who experienced 1 or more AE for a more in-depth evaluation. Nearly three-fourths of this group was Caucasian; 84% and 88% had an ECOG score between 0-1; and the median prostate-specific antigen (PSA) score was 13 ng/ml and 11 ng/ml for apalutamide and enzalutamide, respectively.

Many patients on apalutamide and enzalutamide (43.6% vs. 39.4%, respectively) did not have their AEs resolved. For those who did have toxicities resolved, it took an average of 60 and 56 days for the apalutamide and enzalutamide groups, respectively.

The most common approaches for AE management in the apalutamide and enzalutamide arms were:

Treatment for the AE (36.8% vs. 39.2%, respectively)

The researchers ultimately concluded that there is a resource use burden to manage AEs for these agents, and patients and providers should discuss toxicities before deciding on a treatment regimen.

“The results demonstrate the importance of safety and tolerability, which should be key considerations and shared clinician-patient decision-making regarding androgen receptor inhibitor targeted therapy in nmCRPC patients,” Hussain said.

Jiang S, Varghese D, Appukkuttan S, et. al. Frequency, management, and resource use of adverse events (AEs) in nonmetastatic castrate-resistant prostate cancer (nmCRPC) patients receiving apalutamide or enzalutamide: A real-world study. Presented at: 2021 Genitourinary Cancers Symposium. Feb. 11-13. Virtual. Abstract 217.

While the majority of patients on androgen receptor therapy experienced adverse events, more than a third did not have them resolved. 

Better Treatment Needed for Androgen Receptor Adverse Events

The FDA has accepted and granted a priority review designation to the biologics license application for Vicineum for use in patients with high-risk Bacillus Calmette-Guérin (BCG)–unresponsive non–muscle invasive bladder cancer (NMIBC), according to an announcement from Sesen Bio, the developer of the drug.

The regulatory agency will review the application for Vicineum within 6 months, compared with the standard 10 months from the date of the filing. The FDA is not planning to hold an advisory committee meeting to discuss the application; the agency is slated to make its final decision on Vicineum on, or before, August 18, 2021.

“We have been meeting with the FDA regularly for the past 2 years on the application for Vicineum. We understand the FDA’s position and guidance very clearly and have found the review process to be collaborative and engaging,” Thomas Cannell, DVM, president and chief executive officer of Sesen Bio, stated in a press release. “With these critical FDA decisions, we have reached an inflection point for the Company. In addition to a clear regulatory path forward, we have continued to strengthen our balance sheet in preparation for the potential launch of a product we believe represents a significant advancement over available therapies.”

A recombinant fusion protein, Vicineum, was designed to target epithelial cell adhesion molecule–specific antigens on the surface of tumor cells to deliver 

 Exotoxin A, a potent inhibitor of protein synthesis.

The agent is under examination in the open-label, multicenter, single-arm, phase 3 VISTA trial (NCT024492339) as a treatment for patients with NMIBC who had previously received the current standard of care, BCG.

Results showed that among 89 patients with carcinoma 

 with or without papillary disease that was determined to be refractory or recurred less than 11 months following their last course of BCG, the complete response (CR) rate achieved with Vicineum was 40% (95% CI, 330%-51%) at 3 months. At 6 months, the rate was 28% (95% CI, 19%-39%), whereas it was 21% (95% CI, 13%-31%) and 17% (95% CI, 10%-26%) at 9 months and 12 months, respectively.

Although BCG is an effective option for many patients, tolerability and disease recurrence continue to pose a challenge. If the option does not demonstrate efficacy or the patient can no longer receive it, they are recommended to undergo radical cystectomy. Thus, new options are needed for this population.

The trial completed registration in 2018, with 133 patients enrolled across 3 cohorts based on histology and time to disease recurrence following at least 2 courses of BCG with at least 5 doses in the first course and 2 doses in the second course.

To be eligible for enrollment, patients had to have disease that is refractory or has relapsed after BCG treatment, they had to have a Karnofsky performance status of 60 or greater, and acceptable organ function.

If patients were pregnant or breastfeeding, had evidence of urethral or upper tract transitional cell carcinoma within the past 2 years, had hydronephrosis, received any intravesicular or other chemotherapy treatment within 2 weeks or an investigational 4 weeks before initial dose of the study treatment, they were excluded.

Primary efficacy end points of the trial included CR rate and duration of response (DOR) for patients in cohort 1, while secondary end points comprised time to disease recurrence for patients in cohort 3, as well as time to cystectomy, progression-free survival, event-free survival, and overall survival (OS) for patients across all cohorts.

As of the May 29, 2019 data cutoff, the 82 patients with carcinoma 

 with or without papillary disease that was determined to be refractory or recurred within 6 months of their last course of BCG who comprised cohort 1 experienced CR rates of 39%, 26%, 20%, and 17%, at 3 months, 6 months, 9 months, and 12 months, respectively.

Cohort 2 comprised patients with carcinoma 

 with or without papillary disease that was determined to be refractory or recurred after 6 months, but less than or equal to 11 months, following their last course of BCG. Here, the CR rate at 3 months and 6 months was 57%; it was 43% at 9 months and 14% at 12 months.

The median DOR for patients enrolled to cohort 1 was 273 days (95% CI, 122–not applicable [NA]) per the Kaplan–Meier method. Moreover, additional data from an ad-hoc analysis of pooled data for 93 patients in cohorts 1 and 2 showed that among those who experienced a response to treatment at 3 months, 52% achieved a complete response for 12 months or longer following the start of treatment.

High-risk papillary disease was linked with higher rates of progression and recurrence. The median time to disease recurrence in the 40 patients included in cohort 33 was 402 days (95% CI, 170-NA).

Additionally, of all 133 patients who received Vicineum, more than 75% were estimated to continue to be cystectomy free at 2.5 years. Ad-hoc analysis of responders and non-responders for all patient indicated that about 88% of those who responded to treatment were estimated to remain cystectomy free at 3 years.

Ninety percent of all 133 patients who received the agent were estimated to continue to be free of disease progression at 2 years or longer, and 29% of all patients were estimated to remain event free at 12 months. Also, 96% of all patients were estimated to have an OS of 2 years or longer.

Regarding safety, 95% of toxicities experienced by patients across treatment cohorts were grade 1 or 2 in severity. The most frequently reported adverse effects (AEs) associated with treatment included dysuria (14%), hematuria (13%), and urinary tract infection (12%). Toxicities were determined to be manageable and reversible. Only 3% (n = 4) of patients discontinued treatment with Vicineum because of toxicity. Fourteen percent of patients experienced serious AEs (SAEs), irrespective of treatment attribution. Four treatment-associated SAEs were observed in 3 patients and included grade 33 acute kidney injury, grade 2 pyrexia, grade 4 cholestatic hepatitis, and grade 5 renal failure.

Sesen Bio announces FDA acceptance and priority review of its biologics license application for Vicineum. News release. Sesen Bio. February 17, 2021. Accessed February 17, 2021. 

Sesen Bio reports positive, preliminary data update from phase 3 VISTA trial for high-risk non-muscle invasive bladder cancer. News release. Sensen Bio. August 8, 2019. Accessed February 17, 2021. 

Vicinium treatment for subjects with non-muscle invasive bladder cancer previously treated with BCG. ClinicalTrials.gov. Updated October 14, 2020. Accessed February 17, 2021. 

https://clinicaltrials.gov/ct2/show/NCT02449239

FDA Grants Priority Review to Vicineum for High-Risk, BCG-Unresponsive NMIBC

The FDA has accepted and granted a priority review designation to the biologics license application for Vicineum for use in patients with high-risk Bacillus Calmette-Guérin–unresponsive non–muscle invasive bladder cancer.

Vicineum Granted Priority Review for High-Risk, BCG-Unresponsive Bladder Cancer

Patients with metastatic urothelial carcinoma (mUC) who had a higher tumor mutational burden (TMB) tended to have more immune-related adverse events (irAEs) than those with low TMB. Additionally, high TMB and irAEs rates were associated with better response rates with immunotherapy, according to recent research presented at the 2021 Genitourinary Cancers Symposium.

“It has been shown previously in the literature that TMB serves as a candidate biomarker of clinical outcomes from immune checkpoint inhibitors in urothelial carcinoma. In addition, the immune-related adverse events have been associated with a better [immune checkpoint inhibition] efficacy in multiple cancers,” said study author Elie W. Akl, MD, of the Dana-Farber Cancer Institute.

“So, we hypothesized that the immune response against new antigens is partly responsible for [irAEs] and investigated the association between [irAEs] and TMB and response to [immune checkpoint inhibition].”

The study involved 101 patients with mUC who were being treated with immune checkpoint inhibition (either single-agent or combination) at the Dana-Farber Cancer Institute.

About a third of patients (32%) reported irAEs. Six patients had grade 1 irAEs, 20 patients had grade 2, and 6 patients had grade 3. Those who experienced irAEs had a higher average TMB (15.4/mb) than those without irAEs (9.8/mb). Notably, the cutoff for TMB-high was 10/mb (non-synonymous exonic mutations per megabase).

Ninety-four patients had radiological data available at the time of the study. Among them, 50% of patients with irAEs responded, to therapy, compared to only 16% of patients without irAEs (

“However, when both adverse events and response were included in the multivariable regression, the association between adverse events and TMB was not significant,” Akl explained.

Patients who experienced an irAE and had a high TMB had an overall response rate of 56%, about double the rate of patients who had an irAE but low TMB, at 28.6%. That finding was statistically significant. A total of 21.2% of patients with high TMB but no irAE responded, and 10.3% of patients with low TMB and no irAE responded.

The researchers did not find any correlation between TMB and grading of irAE.

Looking ahead, Akl said the further research is warranted to better understand the associations between TMB, irAEs, and immunotherapy response.

“Further evaluation in metastatic urothelial carcinoma is needed to confirm this relationship between TMB adverse events and response, a larger cohort and explore specific mutations signature that may be associated with immune-related adverse events,” he said.

Patients with metastatic urothelial carcinoma with higher tumor mutational burden and who experienced immune-related adverse events tended to have higher response rates to immune checkpoint inhibitor. 

High TMB, Adverse Events May Predict Immunotherapy Response in mUC 

Reductions in prostate-specific antigen (PSA) screening are likely responsible for the recent increase in metastatic prostate cancer cases in the United States, according to epidemiologic data from a study presented during the 2021 Genitourinary Cancers Symposium.

“To reduce the incidence of metastatic prostate cancer in the United States, we support policies that promote shared decision making to optimize PSA screening, such as the updated United States Preventive Services Task Force [USPSTF] guidelines,” presenting study author Vidit Sharma, MD, a chief resident in the Department of Urology at Mayo Clinic, said during a poster presentation of the data.

PSA screening was found to reduce metastases and mortality in patients with prostate cancer, according to results from the randomized ERSPC trial. However, screening has also been known to result in significant harms from overdiagnosis and overtreatment of low-risk prostate cancer, Sharma noted. As a result, the USPSTGF found insufficient evidence to recommend PSA screening in 2008 and went on to recommend against it in 2012.

“Several subsequent studies have found that there has been a rise in prostate cancer diagnosis since that change,” Sharma said. “Although the implication of these studies is that decreases in PSA screening were responsible for the rise in metastases, this has not been directly demonstrated.”

The objective of this study was to test the hypothesis that reductions in PSA screening were responsible for increased incidence of metastatic prostate cancer at diagnosis. To do this, investigators examined statewide variation in PSA screening, as well as statewide variation in the incidence of metastatic disease at diagnosis from 2002 to 2016.

Investigators extracted age-adjusted incidence of metastatic prostate cancer diagnosis per 100,000 men from the North American Association of Central Cancer Registries for each state. Additionally, survey-weighted PSA screening estimates for men 40 years of age or older were extracted from the Behavioral Risk Factor Surveillance System, which collected data on PSA screening every 2 years from 2002 onward.

These data were then analyzed in a multi-panel time series by state, using a random effects linear regression model, which looked at random effect at the state level, as well as related changes in PSA screening to incidence of prostate cancer metastases within and between states.

Results showed a significant variation in the incidence of PSA screening between states in men aged 40 years or older (range, 40.1%-70.3%). However, after 2010, a significant decrease in the median percentage of PSA screening across all states (range, 61.8%-50.5%) was observed. Additionally, investigators also noted a significant variation in the incidence of age-adjusted metastatic prostate cancer at diagnosis by state (range, 3.3 to 14.3 per 100,000 men) until 2010, when median incidence increased across all states.

Investigators found that states with larger decreases in PSA screening, there was a larger increase in the incidence of metastatic prostate cancer at diagnosis. Data from the random effects linear regression model confirmed that reductions in PSA screening were related to rises in metastatic disease at diagnosis (-14.9; 95% CI, 12.3-17.5 per 100,000; 

“Overall, variation in PSA screening explained 27% of variation in metastatic disease at diagnosis,” Sharma concluded.

Vidit Sharma, Abhishek Venkataramana, et al. Association of reductions in PSA screening across states with increased metastatic prostate cancer in the United States

. 2021;39(suppl 6):228. doi:10.1200/JCO.2021.39.6_suppl.228

Reduction in PSA Screening Associated with Increased Incidence of Metastatic Prostate Cancer in the United States

Reductions in prostate-specific antigen screening are likely responsible for the recent increase in metastatic prostate cancer cases in the United States.

Metastatic Prostate Cancer Rates Rise as PSA Screening Decreases

Sapanisertib failed to show significant activity and a favorable toxicity profile in patients with refractory metastatic renal cell carcinoma (mRCC) regardless of mTOR or PTEN status, according to findings from a phase 2 study (NCT03097328) that were presented during the 2021 Genitourinary Cancers Symposium.

At a median follow-up of 10.4 months (range, 1.0-27.4), the objective response rate (ORR) was 5.3% (n = 2; 90% CI, 1.0%-15.6%). The median progression-free survival (PFS) was 2.5 months (95% CI, 1.8-3.7), and the median overall survival (OS) was 11.2 months (95% CI, 9.3-not reached).

“Sapanisertib had poor tolerability and minimal activity in patients with treatment refractory metastatic RCC, and there was no clear benefit among patients with mTOR or PTEN alterations,” Bradley McGregor, MD, lead study author, and clinical director of the Lank Center for Genitourinary Oncology, senior physician at Dana-Farber Cancer Institute, and instructor of medicine at Harvard Medical School, said in a virtual presentation of the data.

Treatment options following progression on a checkpoint inhibitor and VEGF TKI are limited for patients with mRCC. Approved rapalogs, which have modest activity in mRCC, inhibit only mTORC1, whereas sapanisertib inhibits the entire mTOR pathway by targeting mTORC1 and mTORC2.

The multicenter, single-arm study enrolled 38 patients with clear cell mRCC who had received at least 2 prior lines of therapy and non-clear cell mRCC who had received at least 1 prior line of therapy with an ECOG performance status of 0 to 2.

Patients underwent a mandatory baseline biopsy that evaluated PTEN status and over 477 genes, including TSC1, TSC2, mTOR, PIK3CA, and PTEN, prior to receiving 30 mg of oral sapanisertib weekly.

The primary end point was ORR. Secondary end points included PFS, OS, safety, and toxicity. ORR and PFS by PTEN immunohistochemistry status and oncopanel-identified mutations in the mTOR pathway served as correlative end points.

Regarding patient characteristics, the median age at the time of enrollment was 62 (range, 28-75). The majority of patients had clear cell histology (73.7%; n = 28), followed by non-clear cell RCC (26.3%; n = 10), which encompassed chromophobe RCC (n = 2), papillary RCC (n = 6), translocation RCC (n = 1), and unclassified RCC (n = 1). The majority of patients had intermediate-risk disease (76.3%; n = 29) per International Metastatic RCC Database Consortium risk assessment, followed by favorable- (13.2%; n = 5) and poor-risk disease (10.5%; n = 4).

The majority of patients were heavily pretreated, having received 4 or more prior lines of therapy (39.5%; n = 15). Though, patients who received 1 (13.2%; n = 5), 2 (21.1%; n = 8), and 3 (13.2%; n = 5) prior lines of therapy were also represented. A total of 5 patients (13.2%) had an unknown number of prior treatments.

The majority of patients had received a prior checkpoint inhibitor (75.8%; n = 25) but not an mTOR inhibitor (60.6%; n = 20).

Additional results showed that 2 patients experienced an unconfirmed partial response (PR; 5.3%), 15 patients experienced stable disease (SD; 39.4%), 17 patients experienced progressive disease (44.7%), and 2 patients were not evaluable (5.3%).

The median time on treatment was 1.6 months (range, 0.3-13.8). At the time of data cutoff, 2 patients remained on treatment (5.3%), 36 had discontinued treatment (94.7%), 29 had progressive disease (PD; 76.3%), 4 had unacceptable toxicity (10.5%), 1 withdrew (2.6%), 1 discontinued by patient decision (2.6%), and 1 discontinued by physician discretion (2.6%).

No clear benefit between mTOR and PTEN alterations and clinical benefit with sapanisertib was reported.

Among patients with intact PTEN (n = 12), 1 experienced a PR, 6 experienced SD, and 5 experienced PD. Among patients with diminished PTEN expression or PTEN loss (n = 7), 1 experienced an unconfirmed PR, 2 experienced SD, and 4 experienced PD.

Among patients with an mTOR pathway mutation (n = 6), 1 experienced an unconfirmed PR, 1 experienced SD, and 4 experienced PD. Among patients without an mTOR pathway mutation (n = 21), 2 experienced a PR, 1 experienced an unconfirmed PR, 8 experienced SD, and 9 experienced PD.

Treatment-related adverse effects consisted of nausea (50%; n = 19) fatigue (39%; n = 15, vomiting (34%; n = 13), mucositis (32%; n = 12), anorexia (21%; n = 8), diarrhea (18%; n = 7), rash (18%; n = 7), dyspnea (13%; n = 5), hyperglycemia (13%; n = 5), constipation (11%; n = 4), hyperkalemia (11%; n = 4), cough (8%; n = 3), dehydration (8%; n = 3), dry mouth (8%; n = 3), muscle weakness (8%; n = 3), pruritus (8%; n = 3), hyponatremia (5%; n = 2), elevated creatinine (3%; n = 1), myocardial infarction (3%; n = 1), syncope (3%; n = 1), and pneumonitis (3%; n = 1). No grade 4 or 5 toxicities occurred.

“Additional work is needed to find new targets for patients with advanced RCC,” concluded McGregor.


McGregor BA, Adib E, Xie W, et al. Biomarker-based phase II study of sapanisertib (TAK-228), an mTORC1/2 inhibitor in patients with refractory metastatic renal cell carcinoma (mRCC). J Clin Oncol. 2021(suppl 6):306. doi:10.1200/JCO.2021.39.6_suppl.306

This article was originally published on OncLive as, "Sapanisertib Imparts Poor Activity and Toxicity Profile in Refractory mRCC."

Sapanisertib failed to show significant activity and a favorable toxicity profile in patients with refractory metastatic renal cell carcinoma (mRCC) regardless of mTOR or PTEN status. 

Sapanisertib: Poor Activity, More AEs in mRCC

A shorter course of stereotactic body radiotherapy (SBRT) has been shown to have encouraging efficacy with favorable toxicity when used in patients with high-risk prostate cancer in a multi-institutional, international setting, according to findings from a study published in the 

International Journal of Radiation Oncology, Biology, Physics

Led by investigators at the University of California, Los Angeles (UCLA) Jonsson Comprehensive Cancer Center, the study found that SBRT, which delivers higher doses of radiation therapy over the course of 5 or fewer treatments, is safe and as effective as the standard 45-day course of radiation therapy in this patient population.

 However, further prospective studies are needed to determine the optimal dose and target volume of SBRT in these patients.

“These findings suggest that SBRT, which condenses radiation treatment for prostate cancer into as few as 4-5 sessions (as compared with 20-45 sessions previously), is safe and effective in a broad setting for patients with high-risk prostate cancer,” lead study author Amar U. Kishan, MD, an assistant professor of radiation oncology at the David Geffen School of Medicine at UCLA and researcher at the UCLA Jonsson Comprehensive Cancer Center, told 

. “This has previously been shown in patients with low- and intermediate-risk prostate cancer but extending these findings to [those with] high-risk prostate cancer broadens applicability [of this approach].”

SBRT can be considered for patients with high-risk prostate cancer, as long as they have social or medical hardships that prevent longer courses of radiation therapy, according to 2020 National Comprehensive Cancer Network guidelines. However, guidelines issued by the European Association of Urology are less supportive of this. 

The latter note that the major evidence to support ultra-hypofractionation for this patient population is based on data yielded from a subset of 126 patients who were enrolled to the randomized phase 3 HYPO-RT-PC trial (ISRCTN45905321). Participants did not receive concurrent androgen deprivation therapy (ADT), which is now considered a standard of care for patients with high-risk disease receiving definitive radiotherapy. The authors of that trial concluded that their general conclusions of oncologic equivalency may not be applicable to patients with high-risk prostate cancer. Other published prospective data supporting SBRT for this patient population are limited.

Earlier research led by investigators at UCLA provided significant evidence that a shortened regimen of radiation therapy could be a feasible treatment option for patients with low- and intermediate-risk prostate cancer.

 Investigators decided to broaden this study to see whether a shorter treatment course of radiation could be used in patients with more aggressive disease.

For this research, investigators collected patient-level data from 7 institutions with phase 2 studies and prospective databases. Data were pooled for a total of 344 patients with a minimum follow-up of 24 months. Biochemical recurrence-free survival (BCRFS) and distant metastasis-free survival (DMFS) were estimated using a Kaplan-Meier framework, while Fine and Gray competing risk and Cox proportional hazards regression models were created to evaluate the association between time to biochemical recurrence (BCR) and time to distant metastasis and prespecified variables of interest. Logistic regression models were developed to evaluate associations between acute and late grade 2 or higher genitourinary and gastrointestinal and a priori determined variables, like age, dose per fraction, ADT use, and nodal radiotherapy.

The median follow-up on the study was 49.5 months (range, 35.8-61.9). Seventy-two percent of patients (n = 248) received ADT, with a median duration of 9 months. Results showed that the estimated BCRFS and DMFS rates at 4 years were 81.7% (95% CI, 77.2%-86.5%) and 89.1% (95% CI, 85.3%-93.1%), respectively. Seventeen percent of patients (n = 59) had a BCR and 8% (n = 26) experienced distant metastases.

Multivariable competing risk analyses revealed that 7 Grey (Gy) per fraction versus 8 Gy per fraction was significantly linked with increased risk of BCR (subdistribution HR [sHR], 2.15; 95% CI, 1.07-4.32; P = .03), as was natural log initial prostate-specific antigen (sHR, 1.42; 95% CI, 1.0-1.08; P = .02). Additionally, investigators did not observe any significant predictors of time to distant metastases.

Cause-specific models showed comparable results with regard to BCR and distant metastases. Here, a 1-year increase in age at treatment was found to be significantly linked with increased BCR risk (HR, 1.04; 95% CI, 1-1.07; P = .035).

BCRFS was found to be significantly greater in the patients who received ADT (log-rank P = .009), although no significant difference was observed with DMFS (log-rank P = .097). The cumulative incidence of BCR was observed to be substantially lower in the patients who received ADT (P value, .017 per Gray’s test), while the cumulative incidence of distant metastases was not different (P value, 0.36 per Gray’s test). 

Regarding safety, acute grade 2 or greater genitourinary (GU) toxicity was reported in 18% of patients, while 5% of patients experienced gastrointestinal (GI) effects. No acute grade 3 or higher GU or GI effects were observed. Notably, a dose per fraction of 7 Gy was linked with lower odds of acute grade 2 or higher GU toxicity, while a dose per fraction of 8 Gy was associated with higher odds of this toxicity (odds ratio [OR], 0.09; 95% CI, 0.02-0.48; P = .005).

The 4-year cumulative incidence estimate for late grade 2 or higher GU toxicity was 17.6% (95% CI, 13.6%-21.9%), while this estimate was 6.4% (95% CI, 3.7%-10.1%) for GI toxicity.

Moreover, the crude incidences of late grade 3 or higher GU toxicity was 2.3% versus 0.9% for GI toxicity, with a median time to onset of 21 months and 22 months, respectively.

Although the results of this study highlight the efficacy of this approach, and overall toxicity rates were low and consistent with prior data with SBRT in patients with low- and intermediate-risk disease, the study still had limitations. For one, this analysis focused on multiple single- arm phase 2 studies and prospective registries. Due to the non-randomized nature of the study, this research cannot provide level I evidence to support SBRT for use in this patient population. 

The ongoing randomized PACE-C trial is expected to provide additional level 1 evidence concerning the efficacy of SBRT vs conventional radiotherapy among patients with HRPCa.

“There are several intriguing avenues [for future exploration]. First and foremost, large randomized trials, such as PACE-C run out of the United Kingdom, will be critical to cement SBRT as the standard option, as opposed to a standard option, so we eagerly await that,” Kishan told OncLive. “Second, multiple ongoing studies are [being done] to find out how we can best optimize treatment in patients with more aggressive features, perhaps by adding drugs or selectively increasing the dose, and de-escalating treatments in patients with less aggressive features. Third, technological advances, such as direct magnetic resonance imaging—guided radiotherapy, may help us improve the precision of this treatment further and [this is] being actively studied.”

1. van Dams R, Jiang NY, Fuller, DB, et al. Stereotactic body radiotherapy for high-risk localized CARcinoma of the prostate (SHARP) consortium: analysis of 344 prospectively treated patients. Int J Radiat Oncol Biol Phys. Published online January 22, 2021. doi:10.1016/j.ijrobp.2021.01.016

2. Study finds shorter radiation regimen safe, effective for men with advanced prostate cancer. News release. UCLA Health. January 25, 2021. Accessed January 26, 2021. http://bit.ly/3cfs4MM.

A shorter course of stereotactic body radiotherapy (SBRT) has been shown to have encouraging efficacy with favorable toxicity when used in patients with high-risk prostate cancer in a multi-institutional, international setting, according to findings from a study published in the International Journal of Radiation Oncology, Biology, Physics.

Shorter SBRT Treatment Is Safe, Efficacious in High-Risk Prostate Cancer

“This combination of cabozantinib and nivolumab significantly improved key efficacy measures compared to sunitinib — progression-free survival, overall survival and objective response rate – while showing a low rate of treatment discontinuations due to side effects. The therapeutic benefit demonstrated in CheckMate -9ER and quality of life measures explored emphasize the role of this combination for patients with advanced kidney cancer,” said Toni Choueiri, MD, Director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and the Jerome and Nancy Kohlberg Professor of Medicine at Harvard Medical School.

The approval is based off findings from the phase 3 CheckMate-9ER trial, which analyzed cabozantinib plus nivolumab compared to sunitinib in patients with previously untreated advanced or metastatic RCC. Results, which were published at the European Society of Medical Oncology Virtual Congress, showed that the combination improved overall survival and compared to the sunitinib arm.

CheckMate-9ER findings also showed that the cabozantinib/nivolumab arm doubled average progression-free survival (PFS) over the sunitinib arm, at 16.6 months and 8.3 months, respectively. Objective response rate was also doubled in the cabozantinib/nivolumab arm, 56% versus 27% respectively.

“While significant progress has been made in the treatment landscape for advanced kidney cancer over the last several years, patients still need more therapeutic options to treat this disease as we search for a possible cure,” said Bryan Lewis, President and Co-founder of KidneyCAN.

“As patients are living longer with advanced kidney cancer, focusing on the safety and effectiveness of new treatments has become even more important. The findings for the combination of Cabometyx and Opdivo in the CheckMate -9ER trial make the FDA approval of this combination a notable development for the patient community,” Lewis said.

Adverse events (AEs) with were consistent with what was previously seen with cabozantinib (a TKI inhibitor) and nivolumab (an immunotherapy agent). Common AEs that occurred in 20% or more of patients included: diarrhea, fatigue, hepatotoxicity, palmar-plantar erythrodysesthesia, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough and upper respiratory tract infection

The FDA approved cabozantinib (Cabometyx) plus nivolumab (Opdivo) for the frontline treatment of patients with advanced renal cell carcinoma (RCC).
 

Genitourinary Cancer