693PPOLO: Time to treatment discontinuation and subsequent therapies following maintenance olaparib for patients (pts) with a germline BRCA mutation and metastatic pancreatic cancer (mPC)

Abstract Background In the randomized Phase III POLO trial (NCT02184195), progression-free survival (PFS) for pts with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and mPC was significantly prolonged with maintenance olaparib versus placebo. Maintenance treatment has the potential to prolong time without subsequent chemotherapies and their associated toxicities. Methods Eligible pts had a gBRCAm and mPC that had not progressed following ≥16 weeks of first-line platinum-based chemotherapy. Pts were randomized to receive maintenance olaparib tablets (300 mg bid) or placebo until investigator-assessed progression or unacceptable toxicity. Time from randomization to discontinuation of treatment (TDT), and initiation of first (TFST) and second (TSST) subsequent therapies following discontinuation of study treatment or death, were secondary endpoints, analysed by log-rank test. Follow-up for subsequent therapies took place 30 days after discontinuation, then every 8 weeks. Results 92 and 62 pts were randomized to olaparib and placebo, respectively. TDT, TFST and TSST were meaningfully longer in the olaparib arm (Table). 30 olaparib (32.6%) and 8 placebo arm (12.9%) pts were on study treatment at the data cut-off. 54 (58.7%) and 49 (79.0%) pts, respectively, had discontinued treatment due to progression; 4 (4.3%) and 2 (3.2%), respectively, due to an adverse event. 45 olaparib (48.9%) and 46 placebo arm (74.2%) pts received subsequent treatment; all received chemotherapy in the second line, except for two placebo arm pts who received olaparib. Table:693POlaparib (N = 92)Placebo (N = 62)Time to discontinuation of treatmentEvents, n (%)60 (65.2)53 (85.5)Median, months (95% CI)7.2 (5.5, 10.8)3.8 (3.6, 4.8)Hazard ratio (95% CI)0.45 (0.30, 0.67)Nominal P value0.0001Time to first subsequent therapyEvents, n (%)58 (63.0)46 (74.2)Median, months (95% CI)8.6 (6.2, 12.5)5.7 (4.2, 6.3)Hazard ratio (95% CI)0.50 (0.32, 0.76)Nominal P value0.0013Time to second subsequent therapyEvents, n (%)50 (54.3)39 (62.9)Median, months (95% CI)13.2 (8.8, 20.0)9.2 (8.3, 13.1)Hazard ratio (95% CI)0.68 (0.44, 1.05)Nominal P value0.083 Conclusions Pts with a gBRCAm and mPC received maintenance olaparib for meaningfully longer than placebo. Initiation of subsequent second-line treatment, typically cytotoxic chemotherapy, was delayed for pts in the olaparib arm and data suggest this effect may be maintained through to subsequent third-line therapy. Clinical trial identification NCT02184195. Ed