Neoadjuvant Vs Adjuvant Treatment Strategies for Ovarian Cancer

Rohit Gosain, MD

Rahul Gosain, MD

Martina C. Murphy, MD

In a recent Treatment Algorithms with the Oncology Brothers program, Rohit Gosain, MD, Rahul Gosain, MD, and Martina C. Murphy, MD, discussed updated treatment options for ovarian cancer. Rohit is the medical director of the Roswell Park Hematology Oncology Southtowns and an assistant professor of oncology at Roswell Park Care Network in Buffalo, NY. Rahul is the medical director of the Wilmot Cancer Institute in Webster, NY. Murphy is an associate professor of medicine, the senior associate dean of the Graduate Medical Education (GME) program, and program director for the University of Florida Hematology/Oncology Fellowship at the University of Florida Health.

These experts first discussed post-diagnosis testing and surgery, with a particular emphasis placed on the role of next-generation sequencing in patients with ovarian cancer. Next, the experts discussed adjuvant therapy options following frontline surgery, as well as neoadjuvant therapies, with an assessment of both platinum-based chemotherapy and bevacizumab (Avastin) in both settings.

Furthermore, the experts examined the use of PARP inhibitors in treating patients with BRCA mutations and their adverse effects. The experts then discussed the treatment landscape for platinum-resistant ovarian cancer, before exploring the use of mirvetuximab soravtansine-gynx (Elahere) in patients with HER2-positive ovarian cancer.

Frontline Therapy in Ovarian Cancer

The experts began by discussing frontline treatment for patients following a biopsy-proven diagnosis of ovarian cancer. Murphy explained that staging for ovarian cancer is frequently staged surgically, with the standard of care comprising primary debulking surgery by a gynecologic oncology surgeon. However, she explained that patients who are ineligible for upfront surgery, such as those with medical comorbidities, may be considered for frontline chemotherapy. She then reiterated that a biopsy followed by primary debulking surgery was the standard for diagnostic staging prior to undergoing adjuvant therapy.

Rohit inquired as to whether next-generation sequencing (NGS) or germline testing was used following an ovarian cancer diagnosis. Murphy explained that her practice conducts guideline-recommend genetic testing and germline testing for BRCA mutations,¹ but additionally expressed that her practice utilizes NGS at the time of diagnosis. In contrast to other providers who wait until the time of recurrence to conduct NGS, she conducts testing at the time of diagnosis to better inform treatment decisions.

Neoadjuvant and Adjuvant Treatment Options

Rahul asked Murphy how her practice decides who should be considered for adjuvant therapy and what agents she considers in this setting. She began by expressing that patients with stage II to IV serous ovarian cancer are considered for platinum-based chemotherapy. For patients with stage IA to IB low-grade endometroid tumors, Murphy explained that her practice adheres to the NCCN guidelines and may either observe patients or administer platinum-based chemotherapy.

Murphy further expressed that patients with higher-risk disease, encompassing stage IC or clear cell and high-grade serous histologies, should receive platinum-based chemotherapy, due to the high rate of recurrence despite early-stage designation.

Regarding bevacizumab, Murphy noted, “It is up to the individual [clinician]. I’m a clinician and there’s controversy around bevacizumab because, in all the studies with bevacizumab in the upfront setting, it does have a progression-free survival [PFS] benefit. If you look at the studies, there’s a lot of mixed data about whether or not there’s an actual overall survival [OS] benefit… It’s not wrong to do it in the upfront setting. I tend to reserve bevacizumab for the recurrent setting.”

Rohit then inquired as to whether Murphy used platinum therapy in the neoadjuvant setting and whether there was a role for bevacizumab in the neoadjuvant setting. Murphy expressed that bevacizumab use was dependent on clinician preference, but that her practice avoided so due to logistical difficulties. She then expressed that her practice utilizes the same platinum-based chemotherapy for both neoadjuvant and adjuvant settings.

Subsequently, Rohit asked about treatment cycling in the neoadjuvant and adjuvant setting. Murphy replied that she expressed to patients that they receive 6 to 9 chemotherapy cycles in either treatment setting. She noted that after surgery she likes to give 3 cycles of therapy to make sure the disease is eradicated.

The Role of PARP Inhibitors in Treating Ovarian Cancer

Rahul expressed utilizing both neoadjuvant and adjuvant strategies in a “sandwich” method before inquiring about Murphy’s utilization of PARP inhibitors in patients who are BRCA-positive. Murphy explained that in light of emerging data, PARP inhibitors elicited the greatest benefit in patients with BRCA or BRCA-like mutations and other forms of homologous recombination deficiencies.

Murphy iterated that the benefits associated with PARP inhibitors have to be considered with treatment-related risks, which she emphasized impact on whether to treat patients with them. She explained that she primarily resorts to PARP inhibition as a last resort for patients who have not experienced responses to all other cancer therapy alternatives and for patients with BRCA and BRCA-like mutations.

Rahul then explained that practices often underestimate the adverse effects associated with oral medications. Murphy agreed, suggesting that they can be managed but may still pose risks to patients.

“I have taken patients who were perfectly fine from a hematologic standpoint and made them require transfusions [...] as a result of using these medications. Those are manageable things, but they’re not benign,” Murphy said. “Sometimes we forget that these oral medications, especially because they are taken every day, rather than every 3 or 4 weeks, can have a lot of [adverse] effects that we need to think about.”

Rohit asked about which PARP inhibitors Murphy primarily used in her practice, given an assortment of these agents are approved for ovarian cancer. Murphy expressed that she predominantly uses olaparib (Lynparza), given its effect on deleterious mutations. Alternatively, in patients with BRCA-wild type or unknown status, she uses niraparib (Zejula). She explained that personal preference and experience managing treatment-related adverse effects impact her inclination to use olaparib.

Antibody Drug Conjugates in Relapsed/Refractory Ovarian Cancer

Rohit wondered how Murphy treats patients who are platinum-resistant, experiencing disease progression less than 6 months after platinum-based chemotherapy. Murphy reiterated her use of bevacizumab in patients who are platinum sensitive, before expressing that she tests for folate receptor alpha at the time of diagnosis if platinum resistance emerges, which occurs eventually for most patients with ovarian cancer.

Murphy explained that she utilizes mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer who are receptor-positive, based on data portraying an OS benefit in this indication. Murphy stated that mirvetuximab soravtansine has its own safety concerns before expressing that she utilizes alternative molecular markers and NGS results to guide her next treatment steps.

Rahul then inquired as to whether an overlap between foliate receptor alpha expression and HER2 expression existed, as well as what Murphy’s preferred antibody drug conjugate (ADC) was treating for treating these patients. Furthermore, he contextualized the use of fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) by referring to data published in light of the approval for the agent in patients with unresectable or metastatic HER2-positive tumors.² Notably, a 45% overall response rate was observed in HER2-positive ovarian cancer, according to Rahul.

In response, Murphy explained that she strives to be strategic in how she employs anticancer agents in practice, reinforcing that her preferred frontline therapy for patients with platinum resistance is mirvetuximab soravtansine. Subsequently, she expressed that sequencing and the timing of approvals impact the use of mirvetuximab soravtansine over T-DXd in her practice, but she suggested that the use of T-DXd would not be incorrect if an oncologist had used it as the preferred option.

Citing ‘unique differences’ in ADCs such as between sacituzumab govitecan-hziy (Trodelvy) and T-DXd to treat patients with Trop-2 breast cancer,Rahul followed by asking if Murphy has witnessed any responses sequencing with one ADC after treatment while another failed to elicit a response in patients. Murphy expressed that the opportunity has not presented itself, seeing as mirvetuximab soravtansine is the only FDA-approved ADC in ovarian cancer.

“It is interesting because [mirvetuximab soravtansine] is the first ADC in the ovarian cancer space. I do not know that we have that information yet, so I cannot effectively answer your question,” Murphy said. “There is [much] that we have to learn in this space using [mirvetuximab soravtansine] and I know that it will not be the last [ADC].”

Managing Toxicities with Antibody Drug Conjugates in Ovarian Cancer Treatment

Rohit then asked Murphy if she had any insight into managing adverse effects related to mirvetuximab soravtansine. Murphy began by identifying ocular toxicities related to treatment with the agent emerging from the phase 3 MIRASOL trial (NCT04209855),³ which she expressed is feared by colleagues and patients alike. She then expressed an open discussion regarding the risks of these toxicities with patients prior to starting treatment with mirvetuximab soravtansine, emphasizing that most cases can be managed.

Furthermore, she expressed the need to have a community partner who can conduct slit lamp exams every other cycle to effectively manage ocular toxicities. She explained that these community partners can be either optometrists or ophthalmologists depending on access. She also stated that patients should only receive treatment with mirvetuximab soravtansine if assurances can be made that they will follow up with them.

Rahul followed up by expressing that when considering toxicities, approvals are not the only consideration for treatment usage, highlighting a need within his own practice to be familiar with a treatment and managing its adverse effects when used.

References

1. National Comprehensive Cancer Network. Genetic/familial high-risk assessment: breast, ovarian, and pancreatic, version 2025 Accessed December 3, 2024. https://tinyurl.com/2vd2r4fm
2. FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for unresectable or metastatic HER2-positive solid tumors. News release. FDA. April 5, 2024. Accessed December 3, 2024. https://shorturl.at/hzLQ9
3. Moore KN, Angelergues A, Konecny GE, et al. Mirvetuximab soravtansine in FRα-positive, platinum-resistant ovarian cancer. N Engl J Med. 2023;239(23):2162-2174. doi:10.1056/NEJMoa2309169