AZ’s Lynparza inches towards ‘game changer’ okay in pancreatic cancer

AstraZeneca and Merck & Co are closer to a new use for their PARP inhibitor Lynparza in pancreatic cancer that could spell the end of a lengthy hiatus in new therapies for the disease, after scraping through an FDA advisory committee meeting.

The panel voted by 7 to 5 in favour of approving Lynparza (olaparib) as a first-line maintenance therapy for people with BRCA-mutated metastatic adenocarcinoma of the pancreas who have responded to an initial chemotherapy regimen.

The FDA is due to deliver a verdict on the new marketing application for Lynparza – which is already approved to treat ovarian and breast cancer and is in late-stage development for prostate cancer – before the end of the year. The narrow vote makes the outcome of that review far from certain.

First-line chemotherapy has a notoriously poor efficacy in this setting, with most patients only surviving eight to 12 months from diagnosis, but AZ’s drug has shown it can extend the time it takes before the cancer starts to recur in the POLO trial.

In that study, giving Lynparza to patients with BRCA-mutated pancreatic cancer after chemo extended the time to disease progression or death to 7.4 months, versus 3.8 months with placebo, which was a 47% reduction in risk.

The duration of response with Lynparza was almost 25 months, prompting oncologists to applaud the therapy for offering a “change in patients’ disease trajectory” when the data was revealed at this year’s ASCO meeting.

The close vote shows that the advisory committee verdict wasn’t a done deal, and the FDA reviewer’s briefing document published ahead of the meeting raised concern that the long duration of response with Lynparza wasn’t reflected in an extension in overall survival compared to placebo.

The FDA also raised issues with the small size of the study, some imbalances in the baseline characteristics in enrolled subjects, and the limitations of current imaging techniques used to record disease progression.

The lack of overall survival data was the sticking point for most of the ‘no’ voters in the advisory committee, so it is possible the FDA might opt to wait for the data to mature before making a decision – particularly as the side-effect burden with Lynparza is greater.

Both groups in the trial had an overall survival of around 18 months at the last data cut-off, and a final verdict on that endpoint isn’t due until next year. The FDA reviewer estimates however that the chances of Lynparza showing a significant improvement over placebo on that measure is just 9%.

All that aside, cancer specialists seem excited by the prospect of a new treatment option for this aggressive form of cancer, and last month the US National Comprehensive Cancer Network (NCCN) updated its treatment guidelines to list Lynparza as an option for first-line maintenance, ahead of any formal approval by the FDA.

It seems oncologists are on board with Lynparza in pancreatic cancer, and the FDA must now decide whether it is too. A verdict from the agency is due by 28 December under the terms of Lynparza’s six-month priority review.