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Managed Care in GYN
Recent Developments and Considerations in the Care of Patients With Gynecologic Cancer

Released: May 30, 2024

Expiration: May 29, 2025

Laura R. Bobolts
Laura R. Bobolts, PharmD, BCOP
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Key Takeaways
  • Approvals and guideline recommendations for PARP inhibitors (eg, niraparib, olaparib, and rucaparib) as maintenance therapy for advanced ovarian cancer have evolved recently.
  • Recent clinical data reinforce the addition of PD-(L)1 inhibitors to platinum-based chemotherapy in patients with endometrial cancer, with improvement seen in progression-free and overall survival in some studies.
  • The antibody–drug conjugates mirvetuximab soravtansine, trastuzumab deruxtecan, and tisotumab vedotin have all entered the gynecologic cancer space demonstrating improved responses and/or survival in patients.

The field of gynecologic cancer care is rapidly evolving with the advent of immunotherapy and other targeted therapies for patients with ovarian, endometrial, and cervical tumors. In this commentary, I share a few highlights of the recent clinical updates presented for gynecologic cancers that were covered at a live webinar following the 2024 Academy of Managed Care Pharmacy annual meeting.

Recent Clinical Updates for Ovarian Cancer
We have had recent updates concerning PARP inhibitors in ovarian cancer in the past few years. All 3 PARP inhibitors—rucaparib, olaparib, and niraparib—had FDA indications withdrawn specifically in the treatment setting where they were given as a single agent in patients with later-line recurrent ovarian cancer. The FDA review of confirmatory trials, some of which unfortunately showed a detriment in survival for PARP inhibitor use as single agent treatment in the recurrent setting, led to the manufacturers voluntarily withdrawing the indications for PARP inhibitors as treatment in the recurrent setting. But where we do continue to see PARP inhibitors used most commonly in ovarian cancer is in the first-line setting as maintenance therapy following a complete or partial response to carboplatin/paclitaxel with or without bevacizumab. Now, there were responses across multiple biomarkers, but in patients with homologous recombination deficiency (HRD), which may include those with BRCA1/2 mutation-positive disease and those with genomic instability.  

Another recent change in the ovarian cancer space is that now the National Comprehensive Cancer Network’s (NCCN) guidelines recommend niraparib plus bevacizumab in patients who previously received bevacizumab as part of their primary ovarian cancer therapy and cannot tolerate olaparib with bevacizumab.

A question that now arises is, what if a patient did not receive a PARP inhibitor in the front-line setting as maintenance therapy? A PARP inhibitor could be used in second line as maintenance therapy if the patient had achieved a complete or partial response to platinum-based chemotherapy. It is also worth noting that we typically do not recommend using a PARP inhibitor in patients whose disease has progressed on a PARP inhibitor previously. In summary, PARP inhibitor maintenance with or without bevacizumab in the frontline setting is a cost-effective therapy in advanced disease that is likely to relapse without it.

Another recent development in the management of gynecologic cancers was the agnostic approval of the antibody–drug conjugate (ADC) trastuzumab deruxtecan (T-DXd). T-DXd is a HER2-directed monoclonal antibody together with a topoisomerase 1 inhibitor payload. It was approved for use in patients with solid tumors, including ovarian cancer, who have a HER2 immunohistochemistry score of 3+ and no other satisfactory alternative treatment options available, based on data from the phase II DESTINY-PanTumor02 trial. It is worth noting that T-DXd is highly emetogenic, so patients need that 3 to 4 drug prophylactic antiemetic regimen started 1 day prior to receiving this agent. We also know it can cause interstitial lung disease, which was seen in almost 11% of patients with ovarian cancer. So, we need to monitor patients for any shortness of breath or changes in breathing and ensure imaging and proper referrals are undertaken.

Another agent that recently received accelerated/full FDA approval in ovarian cancer is mirvetuximab soravtansine, an ADC targeting folate receptors, based on data from the phase III MIRASOL trial in patients with platinum-resistant ovarian cancer. Recent data from mirasol showed a survival improvement with mirvetuximab soravtansine when compared with the use of single-agent chemotherapy in that patient population (HR: 0.67).

Recent Clinical Updates for Endometrial Cancer
We also had new developments and updates reported at the Society of Gynecologic Oncology annual meeting for the management of advanced and/or recurrent endometrial cancer. A new standard of care has risen from adding immunotherapy to platinum-based chemotherapy (ie, carboplatin and paclitaxel) in the frontline setting. Recently we saw data presented for the phase III NRG GY018 trial exploring the addition of pembrolizumab to platinum-doublet chemotherapy vs chemotherapy alone, demonstrating progression-free survival (PFS) advantage in patients with mismatch repair deficient (dMMR) status (HR: 0.34; P <.0001). Of note, the median overall survival (OS) for NRG GY018 remains immature at this time. In addition, we saw data presented for the phase III RUBY trial investigating dostarlimab in a similar patient population (but including carcinosarcoma), also leading to an improved 2-year PFS in both dMMR (61.4% vs 15.7%) and MMR proficient (pMMR) patients (28.4% vs 18.8%), as well as 2-yr OS improvement in those patient populations (dMMR: 82.8% vs 57.5; pMMR: 66.5% vs 53.2%). Based on RUBY, dostarlimab is the only immunotherapy currently (as of May 2024) FDA approved in first-line endometrial cancer in combination with carboplatin and paclitaxel, followed by dostarlimab maintenance in patients with primary advanced or recurrent dMMR or microsatellite instability-high endometrial cancer. But on the managed care side, we need to look beyond just FDA labels. When we look within the NCCN compendium, which justifies insurance coverage for patients across the US and Puerto Rico, we see that they support dostarlimab in the similar upfront use in endometrial cancer but irrespective of biomarker status. That is really important, because that can extend off-label use; the company has submitted for FDA review to expand that label for dostarlimab to include irrespective of biomarker status—so also including this patient population that is pMMR or microsatellite stable.

Additional studies with positive data for adding immunotherapy to chemotherapy in the first-line setting include phase III AtTEnd of atezolizumab (median PFS in dMMR: NE vs 6.9 months) and phase III DUO-E exploring the quadruplet of durvalumab plus carboplatin/paclitaxel followed by maintenance durvalumab plus olaparib vs durvalumab plus carboplatin/paclitaxel followed by maintenance durvalumab only vs chemotherapy alone as first-line treatment (median PFS in dMMR: 31.8 vs NE vs 7.0 months; median PFS in pMMR: 15.0 vs 9.9 vs 9.7). DUO-E has been submitted to the FDA for approval consideration. I think it is remarkable because these results support a potential new treatment option for patients with endometrial cancer who are proficient in mismatch repair gene.

We should also keep in mind that with this new standard of care, now you have a 3- or 4-drug regimen, which can lead to more toxicity than 2 drugs. Things that we may need to be considering for all these immune-chemotherapy combinations include alopecia, fatigue, anemia, nausea, diarrhea, and colitis, as well as other immune-related adverse events (AEs) such as hypothyroidism, and pneumonitis. It is important that we stay on top of those toxicities and mitigate them as fast as we can. Studies have found a 2-fold increased risk of a patient being admitted to the hospital and staying as inpatient if they had an immunotherapy-related AE that was not adequately managed. Moreover, these patients also had an 80% higher risk of an emergency room visit. And when you look at the 6-month total cost of care it was $24,301 higher in patients who had an AE with immunotherapy vs those that did not. Much improvement has been achieved in the management of advanced and/or recurrent endometrial cancer over the last couple of years with the addition of immunotherapy to front-line chemotherapy, but we certainly need to watch for toxicities.

Recent Clinical Updates for Cervical Cancer
A key recent development in the managed care of patients with cervical cancer was the conversion of tisotumab vedotin’s accelerated approval to full approval in the first quarter of 2024. The confirmatory phase III innovaTV 301 explored the efficacy and safety of tisotumab vedotin vs single-agent chemotherapy (eg, topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) in patients with recurrent/metastatic cervical cancer after 1 or 2 previous lines of therapy (N = 502). The primary endpoint was OS. Data presented at the European Society of Medical Oncology annual meeting in 2023 showed a significant improvement in survival for tisotumab vedotin vs chemotherapy (median OS: 11.5 vs 9.5; HR: 0.70; P = .0038) in this patient population. Another important update for cervical cancer was that the DESTINY-PanTumor02 trial also included a cohort of 40 patients with cervical cancer. The agnostic approval of T-DXd also applies to those patients with recurrent cervical cancer and no available satisfactory treatment and a HER2 immunohistochemistry 3+.

Your Thoughts?
What are your thoughts or questions on the current developments, clinical trial updates, and FDA approvals for patients with gynecologic cancer? Answer the polling question and join the conversation by leaving a comment.

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