GI cancer

Olaparib delays metastatic pancreatic cancer progression in BRCA carriers

Adding a PARP inhibitor to standard therapy for metastatic pancreatic cancer can achieve substantially better outcomes for a small subgroup of patients with BRCA germline mutations, according to results presented at ASCO 2019.

Data from the POLO trial suggest that olaparib maintenance treatment after platinum-based chemotherapy should be the new standard of care for patients with metastatic pancreatic cancer and a BRCA1 and/or 2 mutation, according to US study investigators.

The phase 3 trial randomised patients who had no disease progression following standard of care platinum-based chemotherapy to oral olaparib tablets 300mg twice daily (n=92) or placebo (n=62).

The primary outcome of median progression free survival was 7.4 months for olaparib treated patients and 3.8 months for the placebo group.

This was a substantial difference in the context of poor outcomes for pancreatic cancer patients, said the study investigators, noting that at two years after randomisation, 22.1% of patients receiving olaparib had no disease progression compared to 9.6% of patients in the placebo group.

Lead author Dr Hedy Kindler of the University of Chicago Medicine said the overall survival data were not yet mature, but the findings for progression free survival were encouraging for a disease where the current median progression free survival for patients after the current standard chemotherapy is about six months and the median overall survival is 8-12 months.

“Roughly one in five patients responded to olaparib for a median of two years, which is truly remarkable for metastatic pancreatic cancer,” she told an ASCO media briefing.

“We conclude that a strategic approach of first line platinum-based therapy followed by olaparib maintenance treatment should become the new standard of care for patients with metastatic pancreatic cancer who have a germline BRCA mutation,” she said.

Commenting on the trial, ASCO expert spokesperson Dr Suzanne Cole, an oncologist at UT Southwestern Medical Center,  said the findings were a “huge step forward” and likely to change practice to biomarker-tailored treatment for the 4-7% of pancreatic cancer patients who harbour a BRCA mutation.

“Now that we have a targeted medication that can benefit patients who have the BRCA mutation when they present with metastatic pancreatic cancer it is our duty to search for this mutation in all our patients with metastatic pancreatic cancer so that we can identify [those] who can benefit from an oral agent that can extend their life,” she said.

However Dr Wells Messersmith, an oncologist at the University of Colorado Comprehensive Cancer Center, stressed that the trial findings applied to only “a subset of a subset” of patients with pancreatic cancer.

He noted that 3300 patients had to be screened for BRCA mutations to recruit about 150 patients for the trial, implying that oncologists would have to “drag the bushes” to find patients.

And while he accepted that the outcomes were  a major improvement for a condition with a gloomy prognosis, he also pointed out to the huge financial cost of olaparib of US$140 a tablet – which translated into about $124,000 for the 7.4 months of progression free survival seen in the POLO trial.

“We can’t ignore the financial toxicity,” he said.

The trial received funding from AstraZeneca and MSD.

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