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Precision Drug Delays Progression of BRCA-related Pancreatic Cancer in Clinical Trial

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A drug that’s designed to target weaknesses inside cancer cells can hold some advanced pancreatic cancers at bay for a short time after chemo, according to new clinical trial results.

The precision drug, called olaparib (Lynparza), delayed the progression of the disease by 7.4 months on average, compared with 3.8 months in those treated with a dummy drug (placebo).

Olaparib is a treatment that’s specially designed to kill cancer cells that carry a fault in the BRCA genes, which help cells repair damage to their DNA.

And the data released at the American Society of Clinical Oncology (ASCO) Annual Meeting, and published in the New England Journal of Medicine, suggest this could be a new approach for a small number of pancreatic cancer patients carrying these faulty genes.

Longer term survival analysis is still needed to gauge the potential impact. But with pancreatic cancer among the most difficult to treat cancers, experts at ASCO were cautiously optimistic about the trial results.

“We’re potentially on the cusp of a new age of treatment for pancreatic cancer, where for the first time we can tailor therapy based on a biomarker and where having a BRCA mutation opens up more treatment options,” said Dr Suzanne Cole in a comment from ASCO.

Progress for PARP inhibitors

Olaparib is among a group of precision drugs called PARP inhibitors. They’re designed to target cells that carry faults in genes that help cells repair damage to their DNA.

Because of these faults, the cells’ repair systems are hampered, and they become reliant on a molecule called PARP. By switching off PARP, olaparib – and other PARP inhibitors – can kick away this crutch and kill the cancer cells.

The drugs have already offered benefits to patients with ovarian and breast cancers, some of which are known to carry faulty BRCA genes.

Now, thanks to technology that can find cancers carrying these faults, trials in other cancers – including pancreatic cancer – have been gathering pace.

Slowing pancreatic cancer progression

The researchers carried out genetic testing on 3,315 people with pancreatic cancer. Of those, 247 were found to have an inherited fault in either the BRCA 1 or 2 genes.

On the trial, 154 patients were treated 4 to 8 weeks after they finished standard chemotherapy treatment – 92 received olaparib and 62 the placebo.

The researchers then looked at the time it took before patients’ cancers got worse, called progression free survival.

Two years after treatment, just over 2 in 10 people (22.1%) treated with olaparib had no cancer progression, compared with 1 in 10 (9.6%) who received the placebo.

Professor Hedy L. Kindler, who led the study from the University of Chicago, said that seeing a fifth of patients with BRCA faults respond to olaparib was “truly remarkable for metastatic pancreatic cancer”.

Side effects were more common among those treated with olaparib. The most serious side effects occurred in 4 in 10 patients (40%) taking the targeted drug, compared with 2 in 10 (23%) taking the placebo. But the researchers said there was no difference in quality of life between the two groups of patients.

Professor Ruth Plummer, director of the Cancer Research UK Newcastle centre, said that based on this trial, olaparib could be viewed as a new treatment option for pancreatic cancer patients with inherited faulty BRCA genes.

But she added that there were still further data needed from the ongoing study to look at how olaparib might impact patient survival.

Should these data prove prositive, the researchers hope that olaparib - which is taken as a pill rather than intravenously like chemotherapy - could be better for patients and help them continue treatment for longer.

Where did these results come from?

The ASCO annual meeting is the largest gathering of clinical cancer experts in the world.

Researchers share preliminary and more advanced results. These come from small, early stage studies through to large randomised clinical trials.

In some cases, the results will go on to change how patients are treated. But most of the results are yet to be published in a scientific journal, so only offer an early glimpse of what these trials may later confirm.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.