A Targeted Drug Approved for Pancreatic Cancer Treatment for the First Time

On 27 December 2019, the US Food and Drug Administration (FDA) approved treatment for deleterious or suspected deleterious germline BRCA mutation (gBRCAm), detected by an approved test, with disease not progressing on first-line platinum- based chemotherapy for at least 16 weeks, in metastatic (stage 4) pancreatic adenocarcinoma (conventional pancreatic cancer) adults receiving maintenance olaparib (Lynparza), a PARP inhibitor and targeted cancer treatment . Thus, advanced pancreatic cancer must have a BRCA mutation and platinum-sensitive disease.

FDA also approved, to select pancreatic patients for olaparib, detection of deleterious or suspected deleterious BRCA1 or BRCA2 germline mutations using BRACAnalysis CDx (Myriad Genetic Laboratories, Inc.) as a diagnostic tool.

POLO: The Study Behind FDA Approval

Efficacy was studied in double-blind, placebo -controlled, randomized, multicenter POLO. Primary endpoint was progression-free survival, duration of treatment disease control; additional endpoints were overall survival and response rate. 

• Genetic testing in 3315 pancreatic cancer patients found 247 with inherited germline BRCA mutations; thus, %7.4 were BRCA-positive . 
• Researchers randomized 154 patients 3:2 into two groups: 92 received olaparib and 62 placebo.
• Treatment began 4 to 8 weeks after the final platinum dose. 
• Two thirds of BRCA mutations were BRCA2, the rest BRCA1.

Summary of POLO Results

• With olaparib, median progression-free survival was 7.4 months , versus placebo at 3.8 months.
• Olaparib reduced progression risk by % 47 versus placebo.
• POLO results in June 2019 at ASCO and simultaneously in NEJM were presented. At that time, overall survival data were immature. At approval, median overall survival was 18.9 months with olaparib and 18.1 with placebo, not significantly different.
• Severe adverse effects (grades 3, 4, or 5) occurred in placebo recipients at %23 versus olaparib at %40. Discontinuation for adverse effects was % 5.5 with olaparib and %1.7 with placebo. Olaparib was well tolerated, with no quality-of-life difference. Common (> %10) trial effects included nausea, fatigue, vomiting, abdominal pain, anemia, diarrhea, dizziness, neutropenia, leukopenia, nasopharyngitis / upper respiratory infection / influenza, arthralgia / myalgia, dysgeusia, altered taste, headache, dyspepsia, reduced appetite, constipation, stomatitis, dyspnea and thrombocytopenia.

The recommended olaparib doseis twice daily with or without food, 300 mg. 

Related Topic

- Latest advances in pancreatic cancer treatment