Sarah Lynam, MD, is an assistant professor in the Division of Gynecologic Oncology in the Department of Reproductive Biology at Case Western Reserve University School of Medicine and an attending physician in the Division of Gynecologic Oncology at the Seidman Cancer Center at the University Hospitals Cleveland Medical Center in Ohio.

Sarah Lynam, MD, discusses the clinical applicability of mirvetuximab soravtansine and trastuzumab deruxtecan in recurrent ovarian cancer.

Dr Lynam on the Clinical Implications of Targeted Therapies in Ovarian Cancer

“[Mirvetuximab soravtansine and trastuzumab deruxtecan] are very new agents that we can add to our armamentarium to better classify treatment and make sure that we're making and sequencing therapies appropriately for patients, because we have these really promising findings in phase 2 [and phase 3] clinical trials that are investigating these drugs, and really understanding how we can best leverage patients’ therapy decisions based off of what their individualized expression patterns are.”

Sarah Lynam, MD, an assistant professor in the Division of Gynecologic Oncology in the Department of Reproductive Biology at Case Western Reserve University School of Medicine, and an attending physician in the Division of Gynecologic Oncology at the Seidman Cancer Center at the University Hospitals Cleveland Medical Center, discussed the clinical applicability of mirvetuximab soravtansine-gynx (Elahere) and fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) for the treatment of patients with ovarian cancer.

As data have emerged from the phase 2 DESTINY-PanTumor02 trial (NCT04482309) and phase 3 MIRASOL trial (NCT04209855), comprehensive biomarker testing has become increasingly important in treatment planning for patients with recurrent ovarian cancer, Lynam began. Evaluating patients for both HER2 and folate receptor α (FRα) expression helps identify patients who may benefit from targeted therapies such as trastuzumab deruxtecan and mirvetuximab soravtansine, she stated. Having this knowledge also allows for more flexibility regarding toxicities, particularly because each agent has its own list of toxicities, Lynam noted. Specifically, with mirvetuximab soravtansine, myelosuppression is a common adverse effect (AEs) observed, based on earlier data, she explained. Additionally, anemia and blood dyscrasias are also common with therapy, she stated. Secondary AEs seen with these 2 agents also include a multitude of gastrointestinal AEs. Of note, patients receiving mirvetuximab soravtansine should be closely monitored for ophthalmologic toxicities, particularly blurred vision following therapy, she emphasized.

Conversely, trastuzumab deruxtecan is associated with a higher incidence of pulmonary toxicity, including pneumonitis or lung inflammation, Lynam said. These safety considerations may influence treatment selection, particularly for patients with preexisting conditions that predispose them to either ocular or pulmonary complications, she concluded.

Videos

Sarah Lynam, MD, details key efficacy data from the phase 2 DESTINY-PanTumor02 trial, evaluating trastuzumab deruxtecan in HER2-expressing solid tumors.

Dr Lynam on the Efficacy of Trastuzumab Detruxtecan in HER2-Expressing Ovarian Cancer

“The analysis of the use of trastuzumab deruxtecan in an ovarian cancer population is [based on] a phase 2 study that looked at patients who had varying levels of HER2 expression for solid tumor malignancies.”

Sarah Lynam, MD, an assistant professor in the Division of Gynecologic Oncology in the Department of Reproductive Biology at Case Western Reserve University School of Medicine, and an attending physician in the Division of Gynecologic Oncology at the Seidman Cancer Center at the University Hospitals Cleveland Medical Center, detailed the efficacy data of fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in the phase 2 DESTINY-PanTumor02 trial (NCT04482309).

The phase 2 analysis that evaluated trastuzumab deruxtecan across multiple solid tumor malignancies demonstrated an overall response rate of 45.0% (95% CI, 29.3%-61.5%) among patients with ovarian cancer treated with the agent, Lynam began. Of note, in the ovarian cohort, the median number of prior lines of treatment was 3, and 35.0% of patients had received 5 or more lines of therapy. In the study, the median overall survival was 13.2 months in all patients with ovarian cancer and 20.0 months in those with a HER2 expression of immunohistochemistry (IHC) 3+. These findings were considered particularly meaningful given that the study population included patients with varying levels of HER2 expression, she noted. Response rates appeared to be higher in patients with the greatest degree of HER2 expression, particularly those classified as HER2 IHC 3+, in which patients also demonstrated a significant duration of therapy response in the trial, she explained. However, these findings remain exploratory, as prospective validation in larger cohorts is still needed, she stated. Multiple phase 3 trials are now ongoing to further assess trastuzumab deruxtecan in epithelial ovarian cancers and to determine its role in the broader treatment landscape.

Furthermore, factors such as HER2 receptor affinity dimerization could influence treatment sensitivity, which emphasizes the complexity of HER2 biology in ovarian cancer and the need to refine biomarker strategies, Lynam asserted. As these studies mature, better characterization of HER2-driven disease may enable more precise patient selection and optimize the use of trastuzumab deruxtecan in a larger patient population with ovarian cancer, she concluded.

Sarah Lynam, MD, highlights the importance of folate receptor–alpha expression testing to inform treatment decision-making in patients with ovarian cancer.

Dr Lynam on the Importance of FRα Expression Testing in Ovarian Cancer

“In my clinical practice, I do test folate receptor–alpha expression early, because that's an important piece of information that we want to have for patients who are developing disease recurrence, and helps us inform and decide if we have this tool to be able to determine what newer options we have available to [patients].”

Sarah Lynam, MD, an assistant professor in the Division of Gynecologic Oncology in the Department of Reproductive Biology at Case Western Reserve University School of Medicine, and an attending physician in the Division of Gynecologic Oncology at the Seidman Cancer Center at the University Hospitals Cleveland Medical Center, highlighted treatment decision-making considerations in clinical practice regarding mirvetuximab soravtansine-gynx (Elahere) for the treatment of patients with ovarian cancer.

Treatment decision-making for patients with ovarian cancer depends on testing, which helps determine patients’ folate receptor–alpha (FRα) expression, Lynam began. She noted that this is essential to determine early on because it’s currently unknown when patients will develop resistance to platinum-based chemotherapy. A significant number of patients eventually develop platinum resistance, either following first-line therapy or after subsequent exposure to a platinum-based regimen, she explained.

Moreover, Lynam noted that in her clinical practice, she tests for FRα expression early in the disease course. The test plays a key role in planning for patients who could develop disease recurrence and helps inform and determine newer treatment options that could be available, she asserted. Since mirvetuximab soravtansine 

 by the FDA in March 2024, the ovarian cancer landscape now has an agent that could improve outcomes regarding overall survival, particularly in patients with platinum resistance, she added. Therefore, identifying patients’ FRα expression early on is important, especially for those who have not received multiple prior lines of therapy and tend to respond well to mirvetuximab soravtansine, which is reflective of the data from the phase 3 MIRASOL trial (NCT04209855), she concluded.

Sarah Lynam, MD, discusses the significance and implications of mirvetuximab soravtansine for the treatment of patients with ovarian cancer.

Dr Lynam on the Significance of Mirvetuximab Soravtansine in Ovarian Cancer

“[Mirvetuximab soravtansine] is truly a revolutionary agent. This was the first antibody-drug conjugate that was [FDA-]approved for use in ovarian cancer…[It] was the first in ovarian cancer to show an improvement in overall survival.”

Sarah Lynam, MD, an assistant professor in the Division of Gynecologic Oncology in the Department of Reproductive Biology at Case Western Reserve University School of Medicine, and an attending physician in the Division of Gynecologic Oncology at the Seidman Cancer Center at the University Hospitals Cleveland Medical Center, discussed the practical implications of mirvetuximab soravtansine-gynx (Elahere) for the treatment of ovarian cancer.

Mirvetuximab soravtansine is a revolutionary agent in the ovarian cancer landscape, notably because it was the first antibody-drug conjugate (ADC) FDA-approved for the treatment of patients with ovarian cancer, Lynam began. Mirvetuximab soravtansine was 

 by the FDA in November 2022 for the treatment of patients with folate receptor α (FRα)–positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who were previously treated with 1 to 3 prior systemic treatment regimens. The regulatory decision was based on the phase 3 SORAYA trial (NCT04296890). Additionally, the 

FDA granted full approval to mirvetuximab soravtansine in March 2024

 for the same patient population, for which the decision was supported by data from the phase 3 MIRASOL trial (NCT04209855).

Furthermore, she noted that other ADCs are beginning to emerge in the gynecologic cancer landscape, namely with the April 2024 FDA approval of tisotumab vedotin-tftv (Tivdak) for the treatment of patients with recurrent or metastatic cervical cancer who have experienced disease progression on or after receiving chemotherapy, Lynam continued. Nevertheless, she emphasized that mirvetuximab soravtansine was the first ADC in ovarian cancer to demonstrate improvement in overall survival. Having a treatment option like mirvetuximab soravtansine is a significant, particularly as the landscape moves toward more personalized and tissue-informed treatment decisions for patients with ovarian cancer, she concluded.

Sarah Lynam, MD

Articles

Dr Lynam on the Clinical Implications of Targeted Therapies in Ovarian Cancer

Dr Lynam on the Efficacy of Trastuzumab Detruxtecan in HER2-Expressing Ovarian Cancer

Dr Lynam on the Importance of FRα Expression Testing in Ovarian Cancer

Dr Lynam on the Significance of Mirvetuximab Soravtansine in Ovarian Cancer