Triple therapy shows promise in non-germline BRCA-mutated ovarian cancer
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Triple therapy with olaparib plus durvalumab and bevacizumab were well-tolerated in patients with non-germline BRCA-mutated, platinum-sensitive, relapsed ovarian cancer, according to data presented at ESMO Virtual Congress 2020.
“Preclinical studies suggest the potential for synergy between PARP inhibitors, such as olaparib, and PD-L1 immune checkpoint inhibitors, such as durvalumab,” Yvette Drew, PhD, of the Northern Centre for Cancer Care at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, U.K., said. “In addition, the combination of olaparib plus a VEGF inhibitor has been shown to increase progression-free survival for women with advanced ovarian cancer in the first-line maintenance setting.”
In the initial ovarian cancer cohort of the MEDIOLA trial, olaparib (Lynparza; AstraZeneca, Merck) plus durvalumab (Imfinzi, AstraZeneca) was well-tolerated as treatment for women with germline BRCA-mutated, platinum-sensitive relapsed disease.
In this presentation, Drew reported results from two additional trials that investigated the combination of olaparib plus durvalumab with or without bevacizumab (Avastin; Genentech) as treatment for women without a germline BRCA mutation.
Patients who had progressed after receiving 1 to 2 prior lines of platinum-based chemotherapy received olaparib 300 mg twice daily and durvalumab 1.5g IV every 4 weeks and bevacizumab 10 mg/kg every 2 weeks (triplet only) until progressive disease. The researchers examined tumors at baseline and every 8 weeks to determine safety and week 24 disease control rate by week 24 (primary endpoints) as well as objective response rates, median duration of response and PFS (secondary endpoints).
The triplet cohort comprised 31 patients and the doublet cohort comprised 32 patients. At the data cut-off, 22% of patients in the doublet cohort and 42% in the triplet cohort remained on treatment.
The disease control rate at 24 weeks was 77% in the triplet cohort and the median PFS was 14.7 months, with four patients in this cohort achieving a complete response, while in the doublet cohort, disease control rate at 24 weeks was 28% and median PFS was 5.5 months, according to Drew. In the triplet cohort, ORRs were 87% and median duration of those responses was 11 months and the response rates were 34% with a median duration of response of 7 months in the doublet cohort.
Further, exploratory analysis suggested that the high response rate in this triplet cohort was not driven by differences in genomic instability status, according to Drew.
“Overall, the safety profile of the combination of olaparib plus durvalumab either with or without bevacizumab was consistent with the known safety profiles of the single agents,” she said.
The most common adverse events in either group were nausea, fatigue, anemia and diarrhea, and 13% of the patients in the triple therapy cohort reported grade 3 or higher hypertension, according to the presentation. Two patients in the doublet cohort and five patients in the triplet cohort discontinued one or more study drug due to an adverse event.
“The triplet combination showed promising efficacy as treatment in the absence of platinum-based chemotherapy and warrants further investigation in this germline BRCA wild-type population,” she concluded. “Building on the preliminary clinical activity observed here in the treatment setting, a phase 3 study assessing the triplet combination as a maintenance treatment in newly diagnosed advanced ovarian cancer patients is underway.”
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Drew Y, et al. Abstract 814MO. Presented at: European Society for Medical Oncology Virtual Congress 2020; Sept. 19-21, 2020.
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