Bevacizumab Rechallenge Benefit in Recurrent Ovarian Cancer?

A new study suggests that a rechallenge with bevacizumab in combination with platinum-based chemotherapy may prolong progression-free survival (PFS) in patients with recurrent ovarian cancer (ROC) who already received this agent during first-line treatment. The study was presented by Italian researchers at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.

Sandro Pignata, PhD, of the Istituto Nazionale Tumori IRCCS (Istituto di Ricerca e Cura a Carattere Scientifico – Oncologico) “Fondazione G. Pascale,” Naples, Italy, and colleagues evaluated whether adding bevacizumab to a platinum-based chemotherapy prolongs PFS for ROC patients for whom the agent failed as first-line therapy. They found that a rechallenge with bevacizumab in combination with platinum-based chemotherapy was associated with a significantly prolonged PFS and no unexpected toxicities.

Bevacizumab is a recombinant humanized monoclonal antibody directed against the vascular endothelial growth factor (VEGF), a pro-angiogenic cytokine. It binds to VEGF and inhibits VEGF receptor binding, preventing the growth and maintenance of tumor blood vessels. Currently, bevacizumab is FDA approved for ROC patients not previously treated with it, and for the treatment of adults with recurrent glioblastoma.

This randomized phase III trial enrolled FIGO stage IIIB–IV ROC patients relapsing at least 6 months after the last dose of platinum. All patients had received bevacizumab during first-line treatment and were randomized to 6 cycles of platinum-based doublets (carboplatin/paclitaxel or

carboplatin/gemcitabine or carboplatin/pegylated liposomal doxorubicin), with or without bevacizumab. Bevacizumab was administered concomitantly with chemotherapy and as maintenance therapy until disease progression.

A total of 405 patients (mean age, 61 years) were enrolled, and the primary endpoint was PFS.  Among these patients, 64% had progressed ≥ 12 months after their last dose of platinum-based therapy, and 72% had progressed after completion of first-line bevacizumab maintenance. After a median follow-up of 20.3 months, there were 304 PFS events and 147 deaths. Median PFS was 8.8 months without bevacizumab and 11.8 months with bevacizumab (HR, 0.51; 95%CI, 0.41–0.64; P < .001). Median OS was similar in the two groups: 27.1 months without bevacizumab and 26.7 months with bevacizumab (P = NS). 

The most common severe side effects (grade 3 or higher) were hypertension (27.5% in the bevacizumab arm vs 9.7% in the non-bevacizumab arm) and proteinuria (4% in the bevacizumab arm vs 0% in the non-bevacizumab arm.