The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:
On December 27, 2019, the Food and Drug Administration approved olaparib (LYNPARZA®, AstraZeneca Pharmaceuticals LP) for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) metastatic pancreatic adenocarcinoma, as detected by an FDA-approved test, whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen.
The FDA also approved the BRACAnalysis CDx test (Myriad Genetic Laboratories, Inc.) as a companion diagnostic for the selection of patients with pancreatic cancer for treatment with olaparib based upon the identification of deleterious or suspected deleterious germline mutations in BRCA1 or BRCA2 genes.
Efficacy was investigated in POLO (NCT02184195), a double-blind, placebo-controlled, multi-center trial that randomized (3:2) 154 patients with gBRCAm metastatic pancreatic adenocarcinoma to olaparib 300 mg orally twice daily or placebo until disease progression or unacceptable toxicity.
The main efficacy outcome measure was progression-free survival (PFS) by blinded independent central review using RECIST 1.1. Additional efficacy outcome measures were overall survival (OS) and overall response rate (ORR).
Median PFS was 7.4 months (95% CI: 4.1, 11.0) for patients who received olaparib compared with 3.8 months (95% CI: 3.5, 4.9) for patients who received placebo (HR 0.53; 95% CI: 0.35, 0.81; p=0.0035). Median OS for olaparib and placebo was 18.9 months (95% CI: 14.9, 26.2) and 18.1 months (95% CI: 12.6, 26.1), respectively (HR 0.91; 95% CI: 0.56, 1.46; p=0.683); ORR among patients who had measurable disease at baseline was 23% and 12%, respectively.
In general, the adverse reaction profile of olaparib observed in POLO is consistent with the known safety profile of olaparib. The most common adverse reactions to olaparib (≥10%) in clinical trials include nausea, fatigue, vomiting, abdominal pain, anemia, diarrhea, dizziness, neutropenia, leukopenia, nasopharyngitis/upper respiratory tract infection/influenza, respiratory tract infection, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation, stomatitis, dyspnea, and thrombocytopenia.
The recommended olaparib dose is 300 mg taken orally twice daily with or without food.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. FDA granted this application priority review.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.