Loading
The first biomarker-directed drug approval in pancreatic cancer, for the roughly 5-7% with inherited BRCA mutations, though it did not extend overall survival.
POLO, trial NCT02184195 sponsored by AstraZeneca and Merck and reported in 2019, produced the first biomarker-directed drug approval in pancreatic cancer, for the roughly five to seven percent of patients with inherited BRCA mutations, though it did not extend overall survival. It randomised 154 patients with germline BRCA-mutated metastatic disease that had not progressed on at least sixteen weeks of platinum chemotherapy to olaparib maintenance or placebo, met its primary progression-free survival endpoint and led to FDA approval in December 2019, but overall survival was no different. OnCo links it to PARP inhibitors and germline testing, to BRCA1 and BRCA2 and PARP as targets. It is a single pivotal trial with no confirmatory study, and whether a progression benefit alone justifies maintenance is the open question.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
154 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survivalprimary | Olaparib maintenance | 92 | 7.4 months | 0.53 (0.35 to 0.82) | 0.004 | link |
| Placebo | 62 | 3.8 months | ||||
| Overall survival | Olaparib maintenance | - | 19 months | 0.83 | - | link |
| Placebo | - | 19.2 months |
This is the European standard the UK and NHS page for pancreatic cancer is compared against; NICE guideline NG85 (2018) covers the same ground with an older evidence base and a narrower set of funded drugs.
Olaparib maintenance remains a standard option because of its progression-free benefit, tolerability and long-term survivors, but patients should know that it has not been shown to extend average survival.
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.
It defines who a homologous recombination result should send to platinum: core-gene and biallelic carriers, germline or somatic, rather than any repair-gene variant.
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 retrospective platinum signal that made platinum-based first-line chemotherapy the standard for BRCA carriers and set POLO's design of olaparib after platinum.
Shares Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up, Metastatic Pancreatic Cancer: ASCO Guideline Update, Genomic methods identify homologous recombination deficiency in pancreas adenocarcinoma and optimize treatment selection, BRCA or PALB2-mutant pancreatic ductal adenocarcinoma.
Shares BRCA or PALB2-mutant pancreatic ductal adenocarcinoma, PARP, Olaparib, BRCA1 / BRCA2 (HRD).
Shares POLO final overall survival: maintenance olaparib versus placebo in germline BRCA-mutated metastatic pancreatic cancer, Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers, POLO: maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer, Genomic methods identify homologous recombination deficiency in pancreas adenocarcinoma and optimize treatment selection.
Shares POLO: maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer, BRCA or PALB2-mutant pancreatic ductal adenocarcinoma, Olaparib, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question.
Shares Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up, Metastatic Pancreatic Cancer: ASCO Guideline Update, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Metastatic pancreatic ductal adenocarcinoma.
Shares POLO: maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer, PARP, Olaparib, BRCA1 / BRCA2 (HRD).
Shares PARP inhibitors, Olaparib, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, BRCA1 / BRCA2 (HRD).
Shares PARP, PARP inhibitors, Olaparib, BRCA1 / BRCA2 (HRD).