Triplet Including Folate Receptor Alpha Antibody–Drug Conjugate Has Activity in Recurrent Ovarian Cancer

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Mirvetuximab soravtansine, a folate receptor alpha-targeting antibody–drug conjugate, combined with carboplatin and bevacizumab (Avastin) is a highly active regimen with favorable tolerability as maintenance treatment in patients with recurrent, platinum-sensitive ovarian cancer, according to results from a phase 1b study presented by David O’Malley, MD, Director, Gynecologic Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, at the European Society for Medical Oncology Virtual Congress 2020.

In the study known as FORWARD II, patients treated with this combination as maintenance achieved an overall response rate of 83%.

FORWARD II evaluated maintenance therapy with the combination of mirvetuximab soravtansine, carboplatin, and bevacizumab in 41 patients with recurrent platinum-sensitive ovarian cancer. Eligibility criteria included no progression within 6 months of the last dose of platinum-containing therapy, folate receptor alpha positivity (≥50% of cells with ≥2 positive staining intensity), ≥1 lesions that met the Response Evaluation Criteria in Solid Tumors version 1.1 criteria for measurable disease, and receipt of 1 to 2 previous lines of treatment. 

The median age of enrolled patients was 63 years. Approximately three-fourths (73%) of patients had received 1 previous line of therapy and 27% had received 2 previous lines. Some 42% had previous exposure to a poly (ADP-ribose) polymerase inhibitor and 24% had previous bevacizumab exposure.

The platinum-free treatment interval was ≤12 months in 54% of patients. Tumor folate receptor alpha expression was high in 49% of patients and medium in the remainder of patients. 

Patients in the FORWARD II trial received a median of 6 cycles of carboplatin, 12 cycles of mirvetuximab soravtansine, and 13 cycles of bevacizumab.

The researchers noted confirmed tumor responses in 34 patients, which included 10 complete responses and 24 partial responses. The confirmed overall response rate was 80% in the 20 patients with high tumor folate receptor alpha expression and 86% in the 21 patients with medium tumor folate receptor alpha expression. The median duration of response was 10.9 months in the overall patient population, and 9.9 months and 13.3 months in patients whose tumors had high or medium folate receptor alpha expression, respectively.

Progression-free survival was 12.8 months in the overall patient population, 12.4 months in patients with high folate receptor alpha tumor expression, and 12.9 months in the medium folate receptor alpha expression subgroup.

The most common treatment emergent–related adverse events (all grades) were diarrhea (83%), nausea and fatigue (76%), thrombocytopenia (71%), blurred vision (68%), and peripheral neuropathy (56%). Grade 3 adverse events occurring in ≥10% of patients were thrombocytopenia (42%), neutropenia (32%), anemia (12%), hypertension (10%), and diarrhea (10%). Approximately 10% of patients experienced grade 4 neutropenia and thrombocytopenia.

Approximately half (54%) of patients discontinued ≥1 drugs due to adverse events: 37% discontinued carboplatin, 32% discontinued mirvetuximab soravtansine, and 5% discontinued bevacizumab.

The researchers concluded that the efficacy outcomes in this heavily pretreated recurrent platinum-sensitive population were encouraging.

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