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Gynecologic cancer patients now have more options with newly approved treatments, including novel immunotherapies, and more treatments are heading toward approval. These options have been guided by tumor biology and have led to response and survival rates that are better than what has been seen in the past.

A review in the by Brian Slomovitz, MD, of Mount Sinai Medical Center in Miami, and colleagues updated the use of these targeted therapies. New research over the past year has led to the incorporation of immunotherapy into the treatment for all patients with endometrial and cervical cancers. Poly (ADP-ribose) polymerase (PARP) inhibitors continue to play a role in the treatment of women with ovarian cancer, particularly in homologous repair deficient tumors. In addition, PARP inhibitors show benefit in challenging subgroups, and biomarker identification has led to the approval of several antibody-drug conjugates (ADCs).

Slomovitz, director of Gynecologic Oncology, further discusses this fast-changing field in the following interview.

How have novel immunotherapies affected the treatment of endometrial cancer?

Slomovitz: Novel new immunotherapies for endometrial cancer have really changed the standard of care for this disease, based on a series of trials that evaluated the role of chemotherapy plus immunotherapy compared with immunotherapy alone.

There is a clear advantage to adding immunotherapy in the first-line management of endometrial cancer. The question is how well does it work. In women who have mismatch repair-deficient tumors, immunotherapy has up to a 72% decreased risk of progression-free survival (PFS), depending on the trial. In patients with proficient mismatch repair proteins, the difference is not as great. However, there is still a benefit in adding immunotherapy.

The addition of PARP inhibitors to cytotoxic chemotherapy and immunotherapy may also improve response to treatment in the mismatch repair-proficient population.

What are some noteworthy immunotherapy treatments in cervical cancer?

Slomovitz: The treatment of cervical cancer has changed over the last year. Novel trials have incorporated immunotherapy in the first-line management of patients with locally advanced cervical cancer when given in combination and after radiation. In addition, in the first-line metastatic setting, adding immunotherapy with antiangiogenic therapy and chemotherapy is based on newly reported data and has also changed standard care.

Immunotherapy is increasingly used in PD-L1-positive cervical cancer. Although immunotherapy is currently approved for recurrent and metastatic disease, recent studies suggest a benefit with the addition of immunotherapy to definitive chemoradiation for stage III/IV locally advanced cervical cancer.

How have PARP inhibitors changed the therapeutic paradigm in ovarian cancers?

Slomovitz: The work on PARP inhibitors has changed the treatment paradigm in women with ovarian cancer. In the first-line setting, PARP inhibitors are indicated in women with BRCA mutations and/or homologous repair deficiency.

Patients with BRCA-mutated and homologous recombination deficiency–positive BRCA-wild type ovarian cancer demonstrate significant PFS and overall survival benefit, while the effect is much more modest in homologous recombination deficiency-negative, BRCA-wild type ovarian cancer. Finding subgroups within patients with homologous recombination deficiency-negative ovarian cancer who may derive benefit from PARP inhibitors remains an area of interest.

How has the development of antibody-drug conjugates [ADCs] led to enhanced therapies in gynecological cancers?

Slomovitz: I believe that ADCs are the future of gynecological cancer treatment. ADCs such as tisotumab vedotin [Tivdak] and mirvetuximab soravtansine [Elahere] have been incorporated nicely into the standard of care for cervical cancer and ovarian cancer. In addition, trastuzumab deruxtecan [Enhertu] recently received a pan-tumor/tumor-agnostic FDA indication, and has shown great activity in women with all gynecological cancers -- specifically with endometrial cancers.

ADCs have the potential to minimize side effects and increase the therapeutic index, making them a compelling treatment option. The FDA approvals for mirvetuximab soravtansine in platinum-resistant ovarian cancer and tisotumab vedotin in recurrent cervical cancer represent areas of unmet need. ADCs are associated with ocular and pulmonary toxicity, gastrointestinal reactions, and peripheral neuropathy. Providers using ADCs should be familiar with required evaluations and mitigation strategies.

What is your main message for practicing oncologists?

Slomovitz: A key message is to keep learning. The field is changing so much, almost on a daily or weekly basis. In order to give our gynecological cancer patients the best treatment, clinicians need to be aware of these changes.

There are still treatments that are needed for patients with little response to current treatments or for those who will progress on these treatments. As the field is moving toward developing more therapies, clinicians need to balance and prioritize treatments and the options for mitigation strategies for our patients.

Read the review here.