Olaparib-bevacizumab PFS benefit in ovarian cancer greatest following upfront surgery

The combination of olaparib and bevacizumab as maintenance therapy for advanced ovarian cancer appears to confer the greatest progression-free survival (PFS) benefit in women without residual macroscopic disease following upfront cytoreductive surgery, according to an analysis of the phase III PAOLA-1* trial.

PAOLA-1 participants were 806 women with advanced high-grade ovarian, fallopian tube, or primary peritoneal cancer who had complete or partial response to first-line platinum chemotherapy plus bevacizumab. They were randomized to receive bevacizumab maintenance therapy (15 mg/kg Q3W for 15 months) plus either olaparib (300 mg BID for 24 months; n=537) or placebo (n=269).

Initial results showed a significant PFS benefit with the addition of olaparib to bevacizumab (median 22.1 vs 16.6 months; hazard ratio [HR], 0.59, 95 percent confidence interval [CI], 0.49–0.72; p<0.001). [N Engl J Med 2019;381:2416-2428]

The present analysis analysed the impact of the two regimens based on timing of surgery and residual tumour status. Fifty-one and 42 percent of patients had upfront and interval surgery, respectively, while 7 percent did not undergo surgery. Regardless of timing, 60 percent had no residual disease post-surgery, while 33 percent had residual macroscopic disease. [SGO 20/20, abstract 34]

While the olaparib-bevacizumab combination led to greater PFS than bevacizumab-placebo across the board, patients who underwent upfront surgery and had no residual disease incurred the greatest benefit (median 39.3 vs 22.1 months; HR, 0.47, 95 percent CI, 0.29–0.75).

Olaparib-bevacizumab also improved PFS compared with bevacizumab-placebo in patients who underwent interval surgery and had no residual disease (median 22.1 vs 17.7 months; HR, 0.61, 95 percent CI, 0.41–0.91), those who underwent interval surgery and had residual disease (median 18.7 vs 12.3 months; HR, 0.70, 95 percent CI, 0.41–1.2), and those who underwent upfront surgery and had residual disease (median 17.6 vs 13.0 months; HR, 0.74, 95 percent CI, 0.48–1.15).

“Maintenance olaparib plus bevacizumab improved outcomes compared with bevacizumab alone in patients with newly diagnosed advanced high-grade serous ovarian cancer regardless of the timing of surgery or residual disease status after surgery. However, the magnitude of the PFS benefit is greatest when surgery achieved complete surgical debulking, particularly in the upfront setting,” said the researchers.

A separate study of patients newly diagnosed with advanced ovarian cancer on maintenance therapy combined individual patient data from the phase III SOLO1** trial (254 and 126 olaparib and placebo recipients, respectively) and the BRCA-mutation subset of the PAOLA-1 trial (151 and 71 olaparib-bevacizumab and bevacizumab-placebo recipients, respectively).

The results suggested an improved PFS at 24 months with olaparib-bevacizumab vs olaparib alone (82 percent vs 73 percent; HR, 0.71, 95 percent CI, 0.45–1.09). [SGO 20/20, abstract 35]

There were also PFS improvements noted with olaparib vs bevacizumab-placebo (73 percent vs 50 percent; HR, 0.48) and with bevacizumab-placebo vs placebo alone (50 percent vs 36 percent; HR, 0.65).

“The results of the population-adjusted indirect comparison suggest that the combination of olaparib plus bevacizumab leads to a potentially meaningful improvement in PFS versus olaparib alone in women with BRCA-mutated newly diagnosed ovarian cancer,” said the researchers.

“The relative clinical benefit of bevacizumab appears to be additive and consistent across regimens, such that its use leads to a similar level of benefit when combined with olaparib and compared with olaparib alone or used as monotherapy and compared with placebo,” they added. However, the researchers advised caution when interpreting the results due to the non-randomized study design.