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In patients with inherited BRCA mutations whose pancreatic cancer had been held in check by platinum chemotherapy, switching to the tablet olaparib roughly doubled the time before the disease grew again compared with placebo. It was the first biomarker-driven approval in pancreatic cancer.
International double-blind randomised phase 3 trial in 154 patients with a germline BRCA1 or BRCA2 mutation and metastatic pancreatic adenocarcinoma that had not progressed during at least 16 weeks of first-line platinum-based chemotherapy, randomised 3:2 to maintenance olaparib 300 mg twice daily or placebo.
Median progression-free survival was 7.4 months with olaparib and 3.8 months with placebo (hazard ratio 0.53); at the interim analysis there was no difference in overall survival. Health-related quality of life was maintained. The FDA approved olaparib for this indication in December 2019.
Germline testing for every pancreatic cancer patient, platinum first line for BRCA carriers, and olaparib maintenance for those who respond are all downstream of POLO.
The document that made biomarker testing part of routine pancreatic cancer care in the United States; the 2018 version it built on fixed the second-line chemotherapy sequence still used in most guidelines.
Family history misses most carriers, so the NCCN and ASCO guidelines moved to testing every patient; each carrier found is a family that can be offered surveillance and a patient who may be eligible for platinum and PARP inhibition.
The genomic case for platinum in BRCA-type pancreatic cancer, four years before POLO built a maintenance strategy on top of it.
Shares Hedy L. Kindler, Talia Golan, POLO, Germline BRCA1/2 pathogenic variant (gBRCAm).
Shares Talia Golan, POLO, Germline BRCA1/2 pathogenic variant (gBRCAm), Germline BRCA mutation (gBRCA).
Shares Germline BRCA1/2 pathogenic variant (gBRCAm), DNA damage response & homologous recombination, Germline BRCA mutation (gBRCA), Double-strand break repair: HR versus end joining.
Shares Germline BRCA1/2 pathogenic variant (gBRCAm), DNA damage response & homologous recombination, Germline BRCA mutation (gBRCA), Double-strand break repair: HR versus end joining.
Shares Germline BRCA1/2 pathogenic variant (gBRCAm), DNA damage response & homologous recombination, Germline BRCA mutation (gBRCA), Double-strand break repair: HR versus end joining.
Shares Germline BRCA1/2 pathogenic variant (gBRCAm), Germline BRCA mutation (gBRCA), BRCA or PALB2-mutant pancreatic ductal adenocarcinoma, BRCA1 / BRCA2 (HRD).
Shares Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer, Germline BRCA mutation (gBRCA), BRCA or PALB2-mutant pancreatic ductal adenocarcinoma, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question.
Shares BRACAnalysis CDx, Germline BRCA1/2 pathogenic variant (gBRCAm), Germline BRCA mutation (gBRCA), Olaparib.