In 2022, the most significant advances in the treatment of gynecologic cancers were achieved for patients with ovarian cancer. While ovarian cancer continues to carry the worst prognosis of all gynecologic cancers, 5-year relative survival has gradually increased, from 34.4% in 1975 to 52.4% in 2014.1
In this Update, we highlight the recent advances in our understanding of targeted therapy in ovarian cancer. We review SORAYA, a trial that demonstrated that mirvetuximab soravtansine, an antibody-drug conjugate, has promising efficacy in platinum-resistant ovarian cancers that overexpress folate receptor α. We also spotlight progress in the treatment of low-grade serous ovarian cancer, another notoriously chemotherapy-resistant disease, in GOG 281/LOGS, a phase 2 study of the MEK inhibitor trametinib. Finally, we discuss emerging long-term follow-up data on poly(ADP-ribose) polymerase (PARP) inhibitors, which are helping to refine the role of these groundbreaking drugs.
New drug approved for platinum-resistant epithelial ovarian cancer—the first since 2014
Matulonis UA, Lorusso D, Oaknin A, et al. Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: results from the SORAYA study. J Clin Oncol. 2023;41:2436-2445. doi:10.1200/JCO.22.01900.
While most patients diagnosed with advanced ovarian cancer will respond to platinum-based chemotherapy, those whose disease recurs eventually develop resistance to platinum agents. Treatment options for platinum-resistant ovarian cancer are limited and prognosis is poor. Most regimens have a response rate of only 10%. Since the approval of bevacizumab combined with chemotherapy in 2014, no new agents have been approved by the US Food and Drug Administration (FDA) for use in platinum-resistant ovarian cancer.
Efficacy shown with mirvetuximab
Recently, Matulonis and colleagues published results of the SORAYA study, a single-arm,phase 2 trial, that examined the efficacy and safety of mirvetuximab soravtansine-gynx among women with platinum-resistant ovarian cancer.2 Mirvetuximab is an antibody-drug conjugate composed of an antibody directed at the folate receptor α attached to a cytotoxic microtubule inhibitor.
The study included 106 patients with platinum-resistant ovarian cancer whose tumors expressed folate receptor α at a high level—a feature of approximately 50% of patients screened for the study. Twenty-nine patients experienced a partial response and 5 had a complete response, corresponding to a remarkable objective response rate of 32.4%. The median progression-free survival was 4.3 months.
Like other antibody-drug conjugates, ocular toxicities, including blurred vision (41%) and keratopathy (29%), were common. However, toxicity was manageable and rarely led to drug discontinuation.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
The FDA has granted accelerated approval to mirvetuximab soravtansine-gynx for women with platinum-resistant ovarian cancer with high folate receptor α expression who have received 1 to 3 prior systemic treatment regimens.
The FDA has granted accelerated approval to mirvetuximab soravtansine-gynx for women with platinum-resistant ovarian cancer with high folate receptor α expression who have received 1 to 3 prior systemic treatment regimens.
Continue to: A novel agent for recurrent low-grade serous ovarian carcinoma...