While it remains the leading cause of death among patients with gynecologic cancers, new treatments are offering patients better outcomes and better quality of life, says Nicole Gaulin, MD, a gynecologic oncologist at Roswell Park Comprehensive Cancer Center. She explains several new treatments now available to patients in addition to clinical trials currently in process at Roswell Park that could help increase response rates for patients in the future.
My name is Doctor Nicole Gollan, and I'm a gynecologic oncologist here at Roswell Park Comprehensive Cancer Center. I'm very excited to discuss all of the new and exciting updates happening in the ovarian cancer space. Ovarian cancer is the leading cause of death from gynecologic malignancy. There's been development of multiple therapeutics across oncology, and one of the most promising developments has been the use of a new drug model called an antibody drug conjugate or an ADC. An ADC utilizes an antibody that recognizes the cancer cell and is connected to a payload, which contains a small packet of cytotoxic chemotherapy. This then gets internalized into the cancer cell to enact cell killing. There are two new ADCs that we use in recurrent ovarian cancer. One of them is called myrvatuximab, sort of tanine or Elaha, and the other is called transtuzumabdexican or N HHER2. Myrvatuximab is comprised of a folate receptor alpha antibody that again recognizes the tumor cell, a cleavable linker, which is then connected to a payload that contains metaninoid DM. which is a potent tubulinbing anti-mitotic agent. Folate receptor alpha is an ideal target because it is specific to the cancer cells, restricted expression on normal cells, and facilitates internalization of large molecules. Several clinical trials have been published recently demonstrating the efficacy of Murvatuximab. Soraya was a phase two clinical trial published in 2022. The results demonstrated a significant improvement in objective response rates at 32.5% in comparison to response rates of 20% or less that we see with standard chemotherapy in this setting, which is truly a remarkable improvement. The results from Soraya are really promising and led to the development of a phase 3 clinical trial called Mirrasol, which was published in 2023. This trial randomized over 400 women to receive either Murbituximab or Investigators' Choice chemotherapy. The results of this trial showed significant improvements in progression free and overall survival, duration of response, and best response in patients who received Murvatuximab. In terms of safety and adverse events related to Mervatuximab, this drug is overall well tolerated. Keratopathy and blurred vision are seen with increased frequency, with antibody. conjugates. These are typically grade 2 or less, easily reversible and often mitigated with the use of eye drops that are standard with each cycle of chemotherapy, along with regular ophthalmologic exams. These trials led to the accelerated approval of Murbituximab by the FDA in 2022 and full approval following the publication of Mirsol in 2023. Murvatuximab is also a preferred regimen with category one designation for patients whose tumors have high folate receptor alpha expression by the NCCM. In an effort to build upon this substantial improvement in survival with Murbtuximab alone, additional research has been performed to investigate whether the efficacy can be boosted when combining with other agents. A clinical trial published in 2023 investigated the efficacy of Murbitutuximab in combination with bevacizumab. Patients with high folate receptor alpha expression had an impressive objective response rate of 48%. And a median progression free survival of 9.7 months. Another ADC that was recently approved was trastuzumabdexokan or and HER2. This ADC recognizes the surface molecule HER2, and the payload is comprised of a potent topoisomerase 1 inhibitor. Destiny Pan Tumor 02 was published in 2023 and demonstrated an overall response rate of 42.5% in the ovarian cancer cohort. This drug is now available to all ovarian cancer patients whose tumor expresses HER2. Here at Roswell Park, we have a clinical trial open utilizing a new ADC against folate receptor alpha. We are the only site in New York State offering this clinical trial, and there's no requirement for folate receptor alpha expression for enrollment. Another exciting development in the treatment of recurrent ovarian cancer is the utilization of immunotherapy, a phase 2 clinical A trial performed here at Roswell Park investigated the efficacy of combination therapy with bevacizumab, oral cyclophosphamide, and pembrolizumab. 40 patients with recurrent ovarian cancer were enrolled, and the results were really impressive. The data demonstrated an objective response rate of 47.5% and immediate progression free survival of 10 months, along with a clinical benefit rate of 95%. Further, this The regimen was incredibly well tolerated, with high scores on quality of life questionnaires throughout their treatment. We use this regimen often in our patients with recurrent ovarian cancer, and because of the research that was performed here at Roswell Park, this regimen is now included on NCCN guidelines. We currently have several clinical trials open, utilizing immunotherapy in conjunction with other agents to create a multi-pronged Approach at treating recurrent ovarian cancer and really harnessing the robustness of the immune system to kill the cancer while sparing normal tissue and thus limiting toxicity. Here at Roswell Park, we have a national clinical trial open that seeks to understand the role that cytotoxic chemotherapy has in newly diagnosed low grade serous ovarian cancers. The name is deceiving because in this case, low grade does not mean easily treated. These ovarian cancer subtypes are similarly often diagnosed at late stage and are notoriously chemo resistant. In contrast to high grade serous tumors, these tumors often express the estrogen and progesterone receptors at a high rate. As such, our treatment paradigm. Often includes maintenance hormonal therapy after the completion of surgical cytoreduction and platinum-based chemotherapy. This is based on retrospective data published in 2017, demonstrating substantial improvement and progression free survival with the use of maintenance hormone treatment. In the recurrent low grade serous carcinoma setting, a phase two clinical trial was recently presented at the Society for Gynecologic oncology annual meeting. Investigating the efficacy of hormone therapy in combination with a CDK 46 inhibitor rivacyclip. 41 patients were enrolled in this trial, and the results demonstrated an objective response rate of 24% and a clinical benefit rate of 86%. There are always new developments in the ovarian cancer space. Given the fact that we have access to all these clinical trials here at Roswell Park. If you have a patient that meets criteria for any of our trials, or is seeking a second opinion, please send them our way.
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