The FDA Oncologic Drugs Advisory Committee has announced a hearing to discuss a supplemental new drug application for olaparib tablets <a>for the maintenance treatment of adult patients with deleterious or suspected deleterious germline <em>BRCA-</em>mutant metastatic pancreatic adenocarcinoma</a> who have not progressed on first-line platinum-based chemotherapy.
The FDA Oncologic Drugs Advisory Committee (ODAC) has announced a hearing to discuss a supplemental new drug application for olaparib (Lynparza) tabletsfor the maintenance treatment of adult patients with deleterious or suspected deleterious germlineBRCA-mutant metastatic pancreatic adenocarcinomawho have not progressed on first-line platinum-based chemotherapy. The hearing is scheduled for December 17, 2019, according to a press release from the FDA.1
Data fromthe phase III randomized, double-blinded, placebo-controlled POLO trialdemonstrated a benefit in progression-free survival (PFS) with olaparib maintenance compared with placebo in patients withBRCA-mutant metastatic pancreatic cancer. Olaparib induced a median PFS of 7.4 months versus 3.8 months with placebo (HR, 0.53; 95% CI, 0.35-0.82;P= .0038). After 2 years, 22.1% of patients in the olaparib arm had no disease progression versus 9.6% in the placebo arm.2,3
The primaryend pointof the POLO trial was PFS by blinded independent review, while secondary end points included overall survival (OS), time from randomization to second progression or death, objective response rate (ORR), disease control rate (DCR), safety, and tolerability. The percentage of patients in the olaparib arm who remained progression-free at intervals 6, 12, 18, and 24 months consistently experienced rates that were more than doubled those in the placebo arm. The rate of PFS at 6 months was 53% versus 23%, respectively.
Investigators noted that the ORR in the olaparib arm was 23.1% versus 11.5% with placebo. In the olaparib arm, 2 patients achieved a complete response. Median duration of response was 24.9 months versus 3.7 months in the olaparib versus placebo arms, respectively.
No difference was noted between arms at the interim analysis of OS at data maturity. The median OS was 18.9 months versus 18.1 months in olaparib and placebo arms, respectively (HR, 0.91; 95% CI, 0.56-1.46;P= .68).
Olaparib did not lead to any new safety signals in the trial. Forty percent of patients in the olaparib arm experienced grade 3 or greater adverse events (AEs) versus 23% in the placebo arm (95% CI, −0.02% to 31.0%). Overall, 5.5% of patients receiving olaparib discontinued treatment due to an AE compared with 1.7% in the placebo arm.
The POLO trial enrolled 154 patients with metastatic pancreatic cancer and either a germlineBRCA1or BRCA2mutation to evaluate the efficacy of the PARP inhibitor. These patients had not progressed on prior frontline platinum-based chemotherapy. They were randomized 3:2 to receive either oral olaparib tablets at 300 mg twice daily (n = 92) or placebo twice daily (n = 62). Treatment began 4 to 8 weeks after the last chemotherapy dose was given, and patients had clinical visits every week for the first 4 weeks, followed by every 4 weeks for the remainder of the time on study treatment.
To be eligible, patients had to have been previously treated for metastatic disease and had not progressed following at least 16 weeks of platinum-based chemotherapy. Patients had to have a known or suspected deleterious germlineBRCAmutation. However, those who were previously treated with a PARP inhibitor were exclude from the trial.