Most patients are fit to receive a PARP inhibitor for the treatment of ovarian cancer, according to Paula Anastasia, RN, MN, AOCN; however, certain patients may need to start on a lower dose.

Anastasia, a gynecologic oncology clinical nurse specialist for UCLA Health, recently presented on 

 Anastasia discussed the circumstances in which a patient may not be fit for PARP inhibition, even if it was standard of care.

Patients who have poor performance status, for example, or other comorbidities may require an adjusted dosage. However, it is important to note that lower doses do not translate to sub therapeutic benefit.

Other important considerations include individual adverse event profiles, chemotherapy responses, and whether a patient is able to adhere to the administration guidelines, as these are oral medications.

Anastasia also illuminates the fact that, for many patients, the price of these therapies represents a major barrier to care. “These medications can be very expensive, and I’ve [seen] copays of $0 and I’ve [seen] copays of $5000 to $10,000,” she said.

According to Anastasia, ineligibility because of financial burden is not talked about in regard to PARP inhibitors, and although there are copay assistance programs, they are largely underutilized. She notes that she has been successful in obtaining grants for her patients and that leveraging pharmaceutical companies can be helpful.

“It can sometimes be time consuming, but the copay assistance programs, and access groups will do some of the legwork for us.”

Videos

Paula Anastasia, RN, MN, AOCN, highlights circumstances in which patients may not be eligible to receive benefit with a PARP inhibitor. 

Paula Anastasia on PARP Inhibitor Ineligibility Factors for Women With Ovarian Cancer

Understanding the role of maintenance PARP inhibitor therapy and the importance of germline testing for all women with a diagnosis of ovarian cancer are 2 areas of importance for oncology nurses, according to Paula Anastasia, RN, MN, AOCN.

Maintenance therapy with PARP inhibitors has been documented to improve progression-free survival (PFS) in women with stage III-IV ovarian cancer following a complete response (CR) or partial response (PR) to platinum-based chemotherapy. Three agents are approved by the FDA for the treatment of ovarian cancer: olaparib (Lynparza), rucaparib (Rubraca), and niraparib (Zejula).

Treatment adverse effects [AEs] of anemia, nausea, and other hematological effects should be monitored with continued communication between patients and nurses.

“When I started [nursing] 30 years ago, my patients who [had] stage 3 [disease], on average, lived 2 years,” said Anastasia, a gynecologic Oncology Clinical Nurse Specialist for UCLA Health. “Now my patients are living 5 years, 10 years, and longer. They may be on chemotherapy on and off for the long term, but there are long-term remissions and treatment breaks, because we have more and more treatments available. The PARP inhibitors are really providing PFS [benefit] and with the recent data from olaparib in SOLO-1 [NCT01844986] and SOLO2 [NCT01874353], we are seeing our patients [remain] on frontline maintenance olaparib post chemotherapy [and are] disease free for 3 to 5 years.”

Anastasia added that there is still a long way to go with defining the role for PARP inhibitors. “Long-term survival has expanded with the use of PARP inhibitors and maintenance therapy. We didn’t have maintenance therapy 3 years ago. Now with all these studies we’re [in the stage of] tweaking and finding the right dose and the right concoction for the right patients.”

®, Anastasia discussed how multipanel testing is key for identifying patients who have a germline mutation and are therefore at risk of developing other cancers and how customization of care, such as changing of dosing, is importance in determining appropriate PARP inhibitor treatments.

Please highlight how PARP inhibitor therapies are changing the field?

[There were updates at] the Society of Gynecologic Oncology and at ASCO. [These] were very exciting…but they’re not ready for primetime. There’s a lot of new information with combination therapy using PARP inhibitors with the goal to extend survival benefit for patients.

The rucaparib study [ATHENA-MONO; NCT03522246], is looking at frontline maintenance therapy, comparing rucaparib with placebo. Right now, there are 2 PARP inhibitors [approved] for frontline maintenance therapy—olaparib and niraparib. Rucaparib is not approved for frontline [maintenance] yet.

[In ATHENA-MONO] rucaparib showed a median PFS [improvement] in patients who have a homologous recombinant–deficiency [HRD] compared with placebo. [The study] was talked about, saying [it would support] a new FDA indication, but fortunately, or unfortunately, the FDA is being very cautious. They are now saying no, we’re not going to provide approval until [the data] reach 50% maturity and that can take another 2 years. These data are still premature [at] 25%. Time is of essence, but it’s also important to have safety data and look at overall PFS and then in addition, overall survival.

What are some key considerations when selecting a PARP inhibitor for your patient?

Eligibility [for the 2 approved PARP inhibitors] is different based on whether they have a germline or a [genomic] tumor mutation. It’s important that if patients don’t have a germline mutation, they should have tumor testing to see if there’s a deficiency in the homologous recombination pathway. If patients have a deficiency, they would be eligible for a PARP inhibitor, [and studies have shown that] patients who have a germline or an HRD-positive tumor have a better clinical benefit with a PARP inhibitor.

Niraparib is approved for all comers, whether they have a germline or tumor mutation. That’s important in determining a PARP inhibitor and personalized and individualized care is important to pay attention to the patient’s prior AEs from chemotherapy.

As we go forward, after frontline therapy, if patients are in a clinical remission or partial remission—which [we expect] 80% of patients will be—[they] will be offered a PARP inhibitor. Most patients who received 1 line of chemotherapy have sturdy bone marrow, but there is a percentage who don’t, so we want to know, how did patients do with their frontline therapy? Did they require growth factors? Were there dose reductions? Do they have a history of hypertension, which may indicate whether they would tolerate niraparib? All those questions personalize care.

What is the nurse’s role in genetic testing and helping patients understand the importance of it, interpreting results, and helping them make sense of what's going on?

I can't emphasize enough that all patients should have genetic testing.

When we talk about genetic testing, germline testing, now we want panel testing because in addition to the 

 pathogenic variants, there are other pathogenic variants in that family [such as] 

. Sometimes, if clinics aren’t experienced in doing genetic testing, then these targets may be missed. We’re fortunate [at UCLA] that we have a genetic counselor on site, and I know that every [practice] does not have that luxury. There are online genetic counselor services and in addition to testing, all patients should also have counseling [and the opportunity] to ask what does this information mean?

If a patient carries a germline mutation there are other cancer risks: breast cancer, pancreatic cancer, melanoma, etc. In addition, if we’ve identified a germline mutation in our patients, we want to do cascade or family testing—siblings, parents, aunts, uncles, cousins. If we can help prevent cancer by testing a family member, we’ve done a very good thing. I think a lot of that is very helpful and there are support groups, for patients who have germline mutations. I think part of our role as nurses is letting them know that this is part of standard of care.

The other thing that we don’t talk enough about is health care disparities. There is so much data out there and not all ethnic groups are having genetic testing. We do a disservice to our patients if we’re not testing, because then they may be missing out on receiving a PARP inhibitor as a maintenance therapy, or in a recurrent setting. Not only is it a hindrance to the patient, but we’re also not doing cascade testing on their family members, and therefore preventing cancers for them as well.

[We also need to be] aware of our own practices and instill trust in our patients because we want what's best for them [and we must discover] what is important to the patient.

What data are available surrounding tolerability and dose changes for patients receiving PARP therapy? What have you found useful in helping patients who may be experiencing toxicities with continued treatment?

I always tell my nurses…you may not be an expert on knowing the doses. That’s what the package inserts are for, that’s what the pharmacist is for. 

Looking at [data from studies of] niraparib, patients who weighed less than 77 kg and/or have platelet [counts] less than 150,000, should be started at 200 mg daily, as opposed to FDA-approved dose, which is 300 mg. I [was involved in] the original studies and saw a tremendous grade 4 thrombocytopenia when these patients were receiving the 300-mg dose. It was almost counterintuitive because we had dose delays and patients couldn’t receive the therapeutic drug on time.

We check their [complete blood count] CBC every week when we first start niraparib. If they’re on olaparib, we check it monthly. The goal is to see their tolerability; we are looking for any hematological changes. 

I remind patients that when they get [intravenous] IV therapy, we are basing those doses on their height and weight, but with oral medications, it’s one size fit all. If we need delay or dose reduce, again, that’s [based on] their body’s metabolism. I remind them that we are individualizing and personalizing their care.

What AEs should patients be looking for when they’re on a PARP inhibitor?

With the first line maintenance patients do so much better and communication is key.

The classic effects are fatigue, nausea, and then hematological AEs. We oversee the hematological AEs and that’s why we really mandate that they have their labs drawn [more frequently at the start] so we can tweak things. 

Nausea is more like underlying queasiness, and I tell patients to take an antinausea medicine at bedtime, just to see if we can mitigate [it].

Are there any patients who may not be a good fit for PARP inhibitors, even when it is standard of care?

I think most patients are fit to have PARP inhibitors; however, sometimes we must start at a lower dose. Just because we’re starting at a lower dose does not mean it’s going to be sub therapeutic. [It’s important to consider] if the patient is able to take oral medications [and if] they are going to be adherent.

There may also be patients who have a poor performance status and have comorbidities. There is a very small percentage of patients for whom [PARP inhibitors] might not be the right fit. But for the majority, paying attention to individual AE profiles, chemotherapy response, and if they benefit from having a lower dose than the FDA approved starting dose [are important considerations].

What kind of conversations need to happen between patients and providers before starting these therapies?

Something we don’t talk about is the financial [burden]. These medications can be very expensive, and I’ve [seen] copays of $0 and I’ve [seen] copays of $5000 to $10,000. There are copay assistance programs, and I don't think we utilize them enough, but I’ve been able to get grants for patients and the pharmaceutical companies have been very helpful.

It can sometimes be time consuming, but the copay assistance programs, and access groups will do some of the legwork for us.

Pthuri B, O’Cearbhaill R, Eskander R, Armstrong D. Frontline PARP inhibitor maintenance therapy in ovarian cancer: a Society of Gynecologic Oncology practice statement. 

 2020;159(1):8-12. doi:10.1016/j.ygyno.2020.07.097

Articles

 Paula Anastasia, RN, MN, AOCN, discusses the value of germline testing 
and the role of maintenance PARP inhibitor therapy in optimized ovarian cancer treatment. 

Nurses Play Key Role in Facilitating Maintenance Therapy With PARP Inhibitors in Ovarian Cancer

Each month, we take a look back at the most popular 

Topics from July 2022 include key advances in cancer survivorship toxicity management and efforts towards targeting 

mutations in the treatment paradigm for patients with pancreatic cancer. Additionally, recently reported data showed the potential quality-of-life benefit observed with ribociclib (Kisqali) for patients with hormone receptor–positive, HER2-negative breast cancer.

Other top stories include an interview with Gretchen McNally PhD, ANP-BC, AOCNP, on the need for naloxone training for oncology nurses and advanced practice providers (APPs) and a conversation between 2 palliative care experts on why buprenorphine should be considered for the treatment of cancer-related pain.

5. Frontline Ribociclib-Related Quality of Life Favorable to Abemaciclib in HR+/HER2-Advanced Breast Cance

Ribociclib was favorable over abemaciclib (Verzenio) in reducing diarrhea, fatigue, appetite loss, and arm symptoms (such as pain or swelling in the shoulder or arm and difficulty raising the arm), according to a matched-adjusted indirect comparison using published data from individual patients treated in the MONALEESA-2 (NCT01958021) and MONARCH-3 trials (NCT02246621).

4. Targeting KRAS Mutations May Help Address Unmet Need in Pancreatic Cancer Treatment

In recent years, the identification of genetic mutations such as 

 in pancreatic cancer has shifted the treatment landscape toward targeted therapies. Despite this progress, combination chemotherapy remains the standard frontline treatment for patients with localized or advanced disease. Today, many investigators are turning their eye to 

 mutations, as these mutations are the most common genetic alterations for patients with pancreatic cancer and may represent a viable treatment landscape, according to Philip A. Philip, MD, PhD, FRCP.

3. Key Advances in Cancer Survivorship Toxicity Management

, Lidia Schapira, MD, FASCO, highlights from the 2022 ASCO Symptoms and Survivorship track anddiscusses key advances in the treatment of toxicities that may present later in cancer survivorship care. She discusses the importance of baseline measurements and health equity considerations in clinical practice and underscores the potential effect evolving technologies may have on the treatment landscape.

2. Are Oncology Nurses Underutilized in Positively Affecting the Opioid Epidemic?

a nurse practitioner in hematology at The Ohio State University Comprehensive Cancer Center– Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, discusses how oncology nurses might have the opportunity to save more lives with proper naloxone training. Responses obtained from nurses and APPs at McNally’s institution demonstrated that they would feel comfortable administering naloxone, provided they had the proper training, and would be interested in pursuing educational trainings on the agent

1. Experts Make the Case for Buprenorphine Use in Cancer-Related Pain Management

At the Annual Meeting on Supportive Care in Cancer, Mary Lynn McPherson, PharmD, BCPS, FAAHPM, and Amy A. Case, MD, FAAHPM, argued that buprenorphine should play a larger role in cancer-related pain management because of its unique pharmacology and consequent safety profile. As a partial agonist, buprenorphine has less μ-receptor signaling, which may result in fewer opioid-related adverse events. However, this does not mean buprenorphine is not an effective analgesic. It has a higher binding affinity compared with most full μ-opioid agonists, suggesting that it is a very effective pain management option.

Each month, we take a look back at the most popular Oncology Nursing News® stories. Here are the top 5 stories from July 2022.


Oncology Nursing News Top Stories: July 2022

Phase 3 findings from the PRIME trial (NCT03709316) showed that Chinese patients with newly diagnosed advanced ovarian cancer who received maintenance therapy with niraparib (Zejula) following complete response (CR) or partial response (PR) to first-line chemotherapy had superior outcomes vs those who received placebo.

Among patients who achieved a CR to frontline chemotherapy, those treated with niraparib (n = 212) achieved a median progression-free survival (PFS) of 29.4 months (95% CI, 19.3–not estimable [NE]) compared with 8.3 months (95% CI, 7.3-12.0) with placebo (n = 103; HR, 0.45; 95% CI, 0.32-0.61; 

 < .001). In the subgroup of patients who experienced a partial response to chemotherapy, those who were treated with maintenance niraparib (n = 43) had a median PFS of 19.3 months (95% CI, 11.1-NE), vs 8.3 months (95% CI, 5.6-11.1) with placebo (n = 26; HR, 0.45; 95% CI, 0.23-0.86; 

Notably, those who were treated with niraparib and achieved a CR to first-line chemotherapy experienced a numerically longer PFS than those who experienced a PR (HR, 0.67; 95% CI, 0.43-1.05).

“In [patients treated with] niraparib, those with a CR achieved numerically longer median PFS than those with a PR, which warrants further investigation in a larger study given the small sample size of the PR subgroup,” Rutie Yin, lead study author, member of the Department of Gynecology and Obstetrics, and the Key Laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education at the West China Second University Hospital at Sichuan University, and colleagues, wrote in a poster of the data presented during the 2022 ASCO Annual Meeting.

Although platinum-based chemotherapy generates responses in patients with advanced ovarian cancer, approximately 75% of patients with advanced disease will relapse within 18 to 24 months of treatment. In April 2020, the 

FDA approved niraparib for the maintenance treatment

 of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a CR or PR to frontline platinum-based chemotherapy, regardless of biomarker status.

 A few months later, in September 2020, 

the China National Medical Products Administration approved niraparib

The PRIME trial was designed to further evaluate the PARP inhibitor in newly diagnosed patients with advanced ovarian cancer who achieved a response following first-line chemotherapy. The trial enrolled patients who were at least 18 years of age with FIGO stage III/IV ovarian cancer who had a high-grade serous or endometroid tumor. Other key inclusion criteria included receiving prior primary or interval cytoreductive surgery and a CR or PR to first-line platinum–based chemotherapy.

Once enrolled, patients were randomized 2:1 to receive 200 mg of oral niraparib or placebo once daily. Those with a body weight of at least 77 kg and a platelet count of at least 150,000 µL were given 300 mg of niraparib or placebo once daily.

Stratification factors included the presence of germline 

 mutations (yes vs no), homologous recombination deficiency status (positive vs negative), prior neoadjuvant chemotherapy (yes vs no), and response to first-line chemotherapy (CR vs PR).

PFS per blinded independent central review in the intention-to-treat (ITT) population served as the primary end point of the trial. Secondary end points included overall survival (OS) and time to next treatment in the ITT population, PFS and OS in the HRD subgroup, and safety.

Prior data presented at the 2022 SGO Annual Meeting on Women’s Cancer

 showed that in the ITT population, treatment with maintenance niraparib resulted a median PFS of 24.8 months (95% CI, 19.2-NE) compared with 8.3 months (95% CI, 7.3-11.1) in the placebo arm (HR, 0.45; 95% CI, 0.34-0.60; 

 < .001).4 Data presented during the 2022 ASCO Annual Meeting further explored the safety and efficacy of niraparib in patients based on their responses to first-line chemotherapy.

Baseline characteristics were comparable across the 4 subgroups of responders. Most patients in each subgroup had FIGO stage III disease, did not receive neoadjuvant chemotherapy, did not have germline 

 mutations, and had optimal residual disease (R0 and R1) following surgery.

Regarding safety, the toxicity profile of niraparib was consistent with what has been reported in prior clinical trials, with no new safety signals revealed.

The rates of any treatment-emergent adverse effects (TEAEs) in the complete responders who received niraparib, complete responders who received placebo, partial responders given niraparib, and partial responders administered placebo were 99.1%, 92.2%, 100%, and 100%, respectively. In the niraparib-treated CR subset and niraparib-treated PR subset, TEAEs leading to dose interruption occurred in 60.8% and 72.1% of patients, respectively. TEAEs resulting in dose reduction occurred in 37.7% and 53.5% of patients, respectively. TEAEs led to treatment discontinuation in 5.7% and 11.6% of patients, respectively.

In the CR and PR niraparib-treated subgroups, the rates of grade 3 or higher TEAEs were 54.2% and 55.8%, respectively. The most common grade 3 or higher TEAEs were anemia (18.9% and 14%), decreased neutrophil count (18.9% and 11.6%), decreased platelet count (12.3% and 23.3%), and decreased white blood cell count (7.1% and 4.7%).

Yin R, Li N, Wu L, et al. Efficacy of niraparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer in phase 3 PRIME study: A subgroup analysis by response to first-line platinum-based chemotherapy. 

. 2022;40(suppl 16):5551. doi:10.1200/JCO.2022.40.16_suppl.5551

FDA approves niraparib for first-line maintenance of advanced ovarian cancer. News release. FDA. April 29, 2020. Accessed July 14, 2022. 

Zai Lab announces NMPA approval of Zejula (niraparib) for first-line maintenance treatment of ovarian cancer in China. News release. Zai Lab Limited. September 10, 2020. Accessed July 14, 2022. 

Li N, Zhu J, Yin R, et al. Efficacy and safety of niraparib as maintenance treatment in patients with newly diagnosed advanced ovarian cancer using an individualized starting dose (PRIME Study): a randomized, double-blind, placebo-controlled, phase 3 trial. Presented at: 2022 SGO Annual Meeting on Women’s Cancer; March 18-21, 2022. Phoenix, Arizona.

Chinese patients with newly diagnosed advanced ovarian cancer whose disease responsed to first-line chemotherapy experienced significantly improved progression-free survival with niraparib. 

PARP Inhibitor Niraparib Shows Efficacy as Maintenance Treatment in Advanced Ovarian Cancer 

Recommendations for the use of liquid biopsies to detect circulating tumor DNA (ctDNA) were recently released by the European Society for Medical Oncology (ESMO). Investigators reviewed available evidence to provide tumor-specific and general consensus on the use of ctDNA and clarify quality standards required for decision-making.

The assay, which is minimally invasive and can provide more convenient and rapid results compared with tissue samples, has become increasingly used in clinical practice to molecularly profile tumors. The release of ctDNA is believed to be proportional to tumor growth with more ctDNA being shed as a tumor grows.

In early-stage cancers, ctDNA has a role in screening, neoadjuvant monitoring, identification of molecular residual disease (MRD), molecular relapse monitoring, and early assessment of treatment response. Of note, the guideline authors state there is a lack of clinical evidence to support the recommendation of ctDNA assays in these areas.

“New technologies currently in development, such as methylation pattern-based sequencing, fragmentation pattern-based sequencing or novel ultra-sensitive mutation detection methods, have the potential to optimize utility in these new settings,” the study authors wrote. “Multiple clinical trials are underway that may provide the evidence base to adopt ctDNA assays for decision making in multiple clinical scenarios.”

However, ctDNA assays have a larger role for patients with advanced disease as it can be used to guide adoptive adjuvant strategies upon clinical relapse, identify biomarkers to guide therapy and monitor response to therapy, and, upon disease progression, ctDNA assays can be used to identify acquired resistance mechanisms and the emergence of driver and resistance clones.

The evaluation of ctDNA varies and a single ctDNA assessment is fit for all purposes. Investigators noted that the ctDNA fraction changes based on tumor features such as extent of necrosis, disease burden, tumor location, inflammation, rates of proliferation and apoptosis, tumor microenvironment and host-related phenomena. Treatments such as chemotherapy, targeted therapy, radiation, and immunotherapy can also affect levels of ctDNA and ctDNA fraction.

Liquid genotyping consists of polymerase chain reaction (PCR)-based technologies and many studies have shown positive predictive values between ctDNA liquid biopsy and tissue-based PCR and next-generation sequencing testing in advanced malignancies (95%-99%). High accuracy of liquid biopsy in breast, gastrointestinal and lung cancer for single-nucleotide variants have been reported in large prospective studies of liquid biopsy.

The ESMO guidelines include tumor-specific recommendations for tier 1 and tier 2 variants across tumor types including the following:

 ctDNA genotyping recommended in treatment-naïve patients with cancer with resistance to prior TKIs. ctDNA testing may not have adequate sensitivity to detect 

 true high copy number gain as resistance mechanism to osimertinib (Tagrisso) or lorlatinib (Lorbrena). Further, amplification and fusion detection is suboptimal with ctDNA assays, and should be repeated in tissue where possible.

mutations should preferentially be tested in ctDNA. 

fusions only when advanced tissue biopsy not available.

 ctDNA testing if tissue not available or when fast turnaround time is needed for urgent therapeutic decision-making.

 V600E/microsattelite instability for chemotherapy-naïve metastatic colorectal cancer is recommended when tissue testing is not feasible or urgent therapeutic decision-making. 

 pathogenic or likely pathogenic somatic variants may be carried out if tissue not available.

 for potential PARP inhibitor therapy. Caution is needed when interpreting results of ctDNA assays due to false-positive CHIP mutations in DNA repair genes.

Pancreatic, hepatocellular, endometrial, urothelial, thyroid, and soft tissue sarcoma

In terms of general tumor site recommendations, the ESMO guideline committee noted the occasions where tissue testing may provide confirmatory or more accurate guidance for treatment decision-making. These include interpretation of pathogenic variants such as 

; retesing results that are deemed “not detected” by ctDNA; and for the detection of fusions and copy number events. Further, liquid biopsy should not be taken when a tumor is responding to treatment.

Liquid biopsy may have limitations for the detection of specific deviations, and they risk false negative results and the authors recommend that clinicians take these into consideration when evaluating the results. A false negative result may occur when a patient’s plasma sample does not have sufficient levels of ctDNA or ‘non-shedding’ happens, preventing the detection of a variant. False positive results may occur when clonal expansion takes place in apoptotic hematopoietic cells, where plasma DNA mainly originates; the frequency of clonal hematopoiesis of indeterminate potential (CHIP) increases with age, previous systemic cancer treatment and smoking. False positives can be minimized with either the sequencing of white blood cell DNA or the pairing sequencing of a tumor tissue sample. Additional limitations of ctDNA testing include a low tumor fraction presence in the sample, which prevents reliable assessment of variant allele fraction and limits copy number alteration analysis.

The guidelines recommend that clinicians consult a molecular tumor board for to assess results.

Pascual J, Attard G, Bidard FC, et al. ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group. 

. Published online July 6, 2022. doi:10.1016/j.annonc.2022.05.520

In early-stage cancers, ctDNA has a role in screening, neoadjuvant monitoring, identification of molecular residual disease (MRD), molecular relapse monitoring, and early assessment of treatment response.



ESMO Guideline on Liquid Biopsy Address Quality Standards for Clinical Implementation

The combination of mental, physical, and emotional toxicities of cancer treatment result in a very large burden for patients, according to Lidia Schapira, MD, FASCO. Therefore, finding innovative strategies to improve supportive care and symptom management should be top of mind for all practicing oncology providers.

Schapira, who is a professor of medicine, and director of the Cancer Survivorship Program, at Stanford University, met with 

® to discuss key takeaways from this year’s Symptoms and Survivors’ track at the 2022 ASCO Annual meeting. Schapira’s clinical research is focused on the psychosocial aspects of cancer care and issues that relate to patient experience and health equity, and she participated on the track as an invited speaker in a poster discussion session.

One key takeaway from the session is the value of uniform baseline measurements in clinical practice, she said.

“Having good baseline measurements in clinical practice, and of course, in research, is essential, especially in the field of symptom management,” she told 

®, explaining that a great example of this was an ASCO presentation on vitamin D insufficiency-related peripheral neuropathy which compared the clinician assessment and patient reported assessment of neuropathy.

In this study, participants were evaluated at baseline for 25-OH-vitamin D (D2 + D3) via LC-MS assay. Investigators used logistic regression to identify the association between vitamin D insufficiency and grade 3 or greater sensory neurotoxicity. Vitamin D insufficiency was defined as 20 ng/mL with higher levels signifying vitamin D sufficient status.

Results were adjusted for paclitaxel regimen assignment, age, self-reported race, and body mass index and found that the rate of grade 3/4 chemotherapy-induced peripheral neuropathy (CIPN) was 21% (n = 397) among patients with sufficient status compared with 14% (n = 794) among those with vitamin D insufficiency (odds ratio [OR], 1.57; 95% CI, 1.14-1.15; 

= .005). After adjusting for covariates, the odds ratio was 1.39 (95% CI, 0.98-1.97; 

“Neuropathy is one symptom that has—for decades—been very difficult for us to properly measure,” Schapira said. “The importance of this is that if we don’t quite understand just how much toxicity somebody is experiencing, we could overdose them and [induce] irreparable harm.”

According to Schapira, routine exams which standardize the measurements evaluated alongside neuropathy, as well as encouraging patients to be completely forthcoming about their experience and the symptoms they may be experiencing before it affects their function or ability to move, is critical in providing better support to patients.

“We need to be more rigorous with measurements and the definitions. It is very important to have [uniform] baseline measurements,” she said. “I was very impressed [with the SWOG investigators] and I certainly know that most of my colleagues do not do such detailed physical exams before they see a patient who is about to [receive a] taxane in their practice. [This was] well done.”

Another symptom which calls for more uniform measurement is fear of cancer recurrence, she added.

“So many cancer survivors endure some level of fear, and we do not typically assess it in a rigorous manner,” she said. “Even in research, there are different scales for measuring worry about recurrence and fear of cancer recurrence. But there are no rigid cut offs that determine what is sort of clinically very meaningful and not.”

With a growing population of cancer survivors, the prevalence of this symptoms is continuing to demand attention as well. Without clear guides and rigorous assessment, it may be unclear to a provider which patients could suffice from clinician reassurance and empathic communication and which patients require expert referrals because of disabling distress.

“This is very difficult to measure in the clinic but can really lead to somebody not being able to work [or] being very affected by these symptoms [in other ways],” she noted.

Of course, Schapira noted that these are just 2 examples where improvements are still needed, and that there are number of other potential symptoms which are hard to assess due, in part, to a lack of uniform measurements—such as hot flashes or cognitive decline, for example. Moving forward, she urges oncologists and oncology care teams to be diligent in their baseline measurements in order to improve clinical assessment capabilities.

Chen CS, McCann SE, Budd GT, et al. Vitamin D insufficiency as a peripheral neuropathy risk factor in White and Black patients in SWOG 0221. 

2022;40(suppl 16):12023. doi:10.1200/JCO.2022.40.16_suppl.12023

Lidia Schapira, MD, FASCO, discusses the importance of rigorous baseline measurement in improving the assessment and management of distressful cancer symptoms.

Uniform Baseline Measurements Are Crucial in Improving Standard of Supportive Care

The FDA has granted priority review to mirvetuximab soravtansine (IMGN853) for the treatment of patients with folate receptor alpha (FRα)–high, platinum-resistant ovarian cancer who have previously received between 1 and 3 systemic therapies.

The biologics license application (BLA), which is supported by findings from the pivotal phase 3 SORAYA trial (NCT04296890), seeks approval of mirvetuximab soravtansine under the accelerated approval pathway. The regulatory agency is scheduled to decide on the application by November 28, 2022, under the Prescription Drug User Fee Act.

“FDA’s acceptance of our BLA under priority review reinforces our belief in the potential for mirvetuximab soravtansine to serve as a new standard of care for patients with FRα-high platinum-resistant ovarian cancer,” Mark Enyedy, president and chief executive officer of ImmunoGen said in a press release. “We are pleased to be one step closer to realizing the promise of our technology and are working closely with FDA to support the evaluation of our application. We are moving quickly to build out the commercial and medical infrastructure required for a successful launch and look forward to the prospect of delivering mirvetuximab soravtansine to patients later this year.”

The global, single-arm SORAYA trial enrolled 106 patients with platinum-resistant ovarian cancer whose tumors expressed high levels of FRα and who had been treated with up to 3 prior regimens, at least 1 of which included bevacizumab (Avastin).

Study participants received intravenous mirvetuximab soravtansine at 6 mg/kg once every 3 weeks. The primary end point was confirmed investigator-assessed objective response rate (ORR), and the key secondary end point was duration of response (DOR). ORR was also assessed by blinded independent central review (BICR).

In the overall population, the median age was 62 years (range, 35-85). Fifty-one percent of patients had received a median of 3 prior lines of therapy (range, 1-4), and 48% had received a prior PARP inhibitor.

The study was designed to rule out a 12% ORR, based on expected outcomes with available single-agent chemotherapy from the AURELIA trial (NCT00976911), which was done in patients with platinum-resistant ovarian cancer who had received 1 or 2 prior lines of therapy.

Top-line data from SORAYA, which were announced in November 2021,2 indicated that the trial met its primary end point, with an investigator-assessed ORR of 32.4% (95% CI, 23.6%-42.2%) in the overall efficacy population. At a median follow-up of 8.1 months, the median DOR was 5.9 months (95% CI, 5.6-7.7).

Full data from the study, which were presented during the 2022 SGO Annual Meeting,3 demonstrated that among the 34 responders, 5 patients achieved a complete response (CR), and 29 experienced a partial response (PR). At a data cutoff of November 16, 2021, the median investigator-assessed DOR was 6.9 months (95% CI, 5.6-8.1), and the median progression-free survival was 4.3 months (95% CI, 3.7-5.1).

In the subset of patients who received a prior PARP inhibitor (n = 50), the agent elicited an ORR of 38.0% (95% CI, 24.7%-52.8%), with a median DOR of 5.7 months (95% CI, 3.5-8.1). In those who did not receive a prior PARP inhibitor (n = 51), the ORR was 27.5% (95% CI, 15.9%-41.7%), with a median DOR of 5.9 months (95% CI, 3.0–not reached).

The BICR-assessed ORR was 31.6% (95% CI, 22.4%-41.9%) among 95 patients, which included a CR rate of 5.3% and a PR rate of 26.3%.

In terms of safety, all-grade adverse effects (AEs) occurred in 86% of patients; these effects were grade 3 in 27% of patients and grade 4 in 1% of patients. Most AEs were low-grade, reversible ocular and gastrointestinal events. Serious grade 3 or higher treatment-related AEs (TRAEs) occurred in 8% of patients.

The most common grade 3 effects with mirvetuximab soravtansine included keratopathy (8%), blurred vision (6%), dry eye (2%), diarrhea (2%), fatigue (1%), asthenia (1%), decreased appetite (1%), and neutropenia (1%). One patient experienced grade 4 keratopathy.

TRAEs led to dose reductions in 19% of patients; 32% of patients experienced dose delays, and 7% required discontinuations.

Additional efficacy and safety data from the mirvetuximab soravtansine program will be presented at the 2022 ASCO Annual Meeting.

ImmunoGen continues to enroll patients to the confirmatory phase 3 MIRASOL trial (NCT04209855), which is intended to convert the potential accelerated approval to full approval. Top-line data from this study are expected to read out in early 2023.

ImmunoGen announces acceptance of biologics license application for mirvetuximab soravtansine in ovarian cancer by US Food and Drug Administration with priority review. News release. ImmunoGen, Inc. May 23, 2022. Accessed July 18, 2022. 

ImmunoGen announces positive top-line results from pivotal SORAYA trial of mirvetuximab soravtansine in ovarian cancer. News release. ImmunoGen Inc. November 30, 2021. Accessed July 18,, 2022. 

Matulonis UA, Lorusso D, Oaknin A, et al. Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression results from the SORAYA study. Presented at: 2022 SGO Annual Meeting on Women’s’ Cancers; March 18-21, 2022; Phoenix, AZ. Abstract 242.

Mirvetuximab soravtansine (IMGN853) has been granted priority review by the FDA for the treatment of patients with FRα-high, platinum-resistant ovarian cancer who have previously received between 1 and 3 systemic therapies.

Mirvetuximab Soravtansine Is Under Priority Review for FRα-High, Platinum-Resistant Ovarian Cancer

The addition of olaparib (Lynparza) to bevacizumab (Avastin) significantly delayed the onset of treatment-related toxicities in patients with newly diagnosed, advanced ovarian cancer, compared with placebo, according to a subanalysis of the phase 3 PAOLA-1/ENGOT-ov25 trial (NCT02477644). Findings were presented during the 2022 Annual ASCO meeting.

In the intention-to-treat population, the median duration of time without symptoms or toxicity for all adverse events (AEs) grade 2 or greater was 14.1 months (95% CI, 12.5-16.1) in the bevacizumab/olaparib arm and 7.7 months (95% CI, 5.9-9.1) in the placebo arm. The median onset for grade 2 or higher toxicities with symptoms was 17.2 months (95% CI, 16.0-20.1) vs 11.3 months (95% CI, 9.7-13.6), respectively.

Moreover, among patients who experienced grade 2 or higher AEs directly related to olaparib, the median duration was 21.9 months (95% CI, 20.2-22.5) vs 16.6 months (95% CI, 14.6-18.0), respectively.

“The substantial progression-free survival [PFS] benefit provided by maintenance olaparib plus bevacizumab was supported by significant TWiST [time without symptoms or toxicity] benefits—almost twice the median duration [compared with the control group],” Florence Joly, MD, PhD, Centre François Baclesse, said in a presentation of the findings. “Notably, in the HRD [homologous recombination deficiency]-positive group, [there was] almost triple the median TWiST.”

PAOLA enrolled individuals with newly diagnosed stage II-IV, high-grade, serious, or endometroid ovarian, fallopian tube and/or primary peritoneal cancer following frontline treatment with platinum-taxane based chemotherapy plus 2 or more cycles of bevacizumab and upfront or interval debulking surgery. Patients were randomly assigned 2:2 to receive either olaparib tablets at 300 mg twice daily or placebo for at least 2 years, in addition to bevacizumab, as maintenance therapy.

Previously reported findings showed that maintenance olaparib plus bevacizumab yielded superior PFS compared with bevacizumab plus placebo, following frontline treatment with platinum-based chemotherapy and bevacizumab. Of note, patients who tested positive for HRD (

mutation and a genomic instability) had a pronounced benefit from the drug combination, and experienced a median PFS of 37.2 months, compared with 17.7 months compared with bevacizumab and placebo.

At the 2022 ASCO meeting, investigators reported on safety, the trials’ secondary end point. Specifically, the TWiST analysis captured outcomes between randomization and disease progression. Patients were stratified by HRD status, and 3 different approaches were used to understand significant toxicities within the trial: investigators reported on all grade 2 or higher AEs, all grade 2 or higher AEs with symptoms, and all grade 2 or higher AEs selected to be linked with olaparib (ie, fatigue, nausea, vomiting, and anemia).

In the subset of patients with HRD-positive disease, the median duration of time without symptoms or toxicity for all AEs grade 2 or greater was 24.4 months (95% CI, 19.3-not estimable [NE]) in the olaparib arm and 7.4 months (95% CI, 5.8-11.2) in the placebo arm (

< .0001). For grade 2 or greater toxicities with symptoms, the median duration was 36.6 months (95% CI, 22.4-NE) vs 12.6 months (95% CI, 9.8-15.6), respectively (

< .0001). For severe AEs directly related to olaparib, the median duration was 36.6 months (95% CI, 31.9-NE) vs 17.4 months (95% CI, 15.1-19.4), respectively (

Among patients whose HRD status was negative or unknown, the median duration of time without symptoms or toxicity for all AEs grade 2 or greater was 8.5 months (95% CI, 6.8-11.4) in the olaparib arm and 7.7 months (95% CI, 5.9-9.1) in the placebo arm (

= .1840). For grade 2 or greater toxicities with symptoms, the median duration was 11.5 months (95% CI, 10.0-14.9) vs 10.5 months (95% CI, 8.5-14.0), respectively (

Moreover, among HRD negative patients who experienced grade 2 or higher AEs directly related to olaparib, the median duration was 16.6 months (95% CI, 14.9-18.0) vs 15.6 months (95% CI, 13.8-18.1), respectively 

Joly F, Chabaud S, Cropet C, et al. Time without symptoms or toxicity (TWiST) in patients with newly diagnosed advanced ovarian cancer receiving maintenance olaparib or placebo plus bevacizumab: analysis of PAOLA-1/ENGOT-ov25 phase III trial. 

 2022;40(suppl 16):5562. doi:10.1200/JCO.2022.40.16_suppl.5562

Patients receiving bevacizumab plus olaparib to treat newly diagnosed ovarian cancer experienced significantly longer time without signs of toxicity compared with placebo.

Bevacizumab With Olaparib Extends Time to Toxicity in Patients With Newly Diagnosed Ovarian Cancer 

Naloxone (Narcan) training for oncology nurses and advanced practiced providers (APPs) may be an opportunity to decrease addiction stigma and save lives, according to Gretchen McNally, PhD, ANP-BC, AOCNP.

McNally, who is a nurse practitioner in hematology at The Ohio State University Comprehensive Cancer Center– Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC), recently presented during the 47th Annual Oncology Nursing Society (ONS) about how oncology nurses might have the opportunity to save lives with proper naloxone training. Responses obtained from nurses and APPs at McNally’s institution demonstrated that they would feel comfortable administering naloxone, provided they had the proper training, and would be interested in pursuing educational trainings on the agent.

“This represents an opportunity for oncology nurses and APPs to positively impact the opioid epidemic, for not only patients affected by cancer, but there may be a positive trickle-down effect on families and communities,” said McNally in a presentation of the findings.

®, McNally walked through the background of Project Dawn, which stands for “deaths avoided with naloxone,” the significance of the findings of her research, and what oncology nurses should understand about naloxone’s role in the opioid epidemic.

“[Project Dawn] is partnered with several of the health care systems, including Ohio State,” McNally said. “Project Dawn supplies free naloxone to [individuals] at risk of an opioid overdose—patients who have an opioid use disorder, [have had] a previous overdose, or [are receiving] a high dose of pain medications,” she explained. 

“In October of 2021, [Project Dawn was] rolled out at the [OSUCCC]. I thought it was very innovative. They had a short 14-minute video that went through recognizing an opioid overdose and how to administer the naloxone, which in the community is usually [administered] as a nasal spray [but in] the hospital or it’s usually administered intravenously or intramuscularly.”

“I think that this is an opportunity to develop creative or innovative strategies to train health care providers and nurses,” she added. “If you think of how many nurses work at the hospital, and then go into the communities, they could really make a huge difference.”

“I always go back to thinking about Jan Rader, who was a fire chief in West Virginia. She gave a TED talk in 2019 [and] said, ‘We all have a role to play in ending the opioid epidemic, and what role will you play?’ As an oncology nurse or provider, you [may] not really think that addiction affects your patients, [but] it affects so many people, and if we can just make a small difference and save 1 life, we’re making an impact.”

McNally and coinvestigators conducted a hospital-wide survey of multidisciplinary oncology health care providers over a 4-week period. Respondents were queried about their experience and knowledge surrounding opioid use disorders. The results presented during ONS highlighted responses on the providers’ knowledge of naloxone administration.


Overall, 698 participants were included in the sample. Among these were 180 APPs and 518 nurses, and the response rates were 50% and 43%, respectively. The mean age of participants was 40.2 years for APPs and 38.4 years for nurses. Most participants were female (n = 641, 91.8%) and White (n = 631, 90.4%). The percentage of respondents who had worked in oncology for over 5 years was 62.3% for APPs and 49.7% for nurses.

Participants were asked to respond to the following statements:

“I feel comfortable administering naloxone in the community”

“I would feel comfortable with training”

“Would you be interested in attending a naloxone training class?”

For the first question, “I feel comfortable administering naloxone in the community”, a greater number of APPs (39.4%; n = 69) compared with nurses (29.1%; n = 145) responded “no.” However, the majority of both nurses (64.2%; n = 309) and APPs (60.1%; n = 104) answered “yes” to the second question, “I would feel comfortable with training.”

Gretchen McNally PhD, ANP-BC, AOCNP, discusses the potential impact advanced practice providers and nurses could have in the opioid pandemic if the correct educational opportunities were available. 

Gynecologic Cancers