So far, 2 cohorts of DRUP have completed the first stage: 1 showed positive results, the other had negative results. In the first cohort, 30 patients whose cancers exhibited microsatellite instability were treated with nivolumab, and it produced a response in 19 of them (1 patient [3%] had a complete response, 11 patients [37%] had a partial response, and 7 patients [23%] had stable disease at ≥16 weeks).

The second cohort included patients with microsatellite-stable colorectal tumors that had low mutational burden. These patients received pembrolizumab, but none of the patients experienced remission, and the cohort was closed.

Both DRUP and TAPUR have emphasized the importance of documenting the failures, as well as the successes, of off-label therapies, to avoid wasting time on a treatment that is unlikely to help. 

But even the failures may warrant a second look, cautioned Razelle Kurzrock, MD, director of the University of California, San Diego, Moores Center for Personalized Cancer Therapy. “The part we have to be careful about is where it fails — [and if it fails,] not assuming the drug doesn’t work, or the matching doesn’t work,” she said. If a cancer carries multiple molecular targets, for instance, the drug might need to be used jointly with other targeted therapies in a combination unique to that patient. “What the genomics has unveiled,” noted Dr Kurzrock, is that metastatic tumors are complicated, and they are usually distinct from one another.

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One huge accomplishment in all of these studies has been getting buy-in from the various drug companies that manufacture the therapies being tested. “Getting all these companies, which are often competitors, to play in the sandbox together has been one of the greatest achievements of ASCO [the American Society of Clinical Oncology],” said Ajjai Alva, MBBS, of the University of Michigan in Ann Arbor, who is an investigator on the TAPUR study. Pharma companies can be held liable if off-label treatments do harm, and giving away drugs to anyone who asks can look like illegal marketing.

By collecting these data in a systematic way, these trials will not only open up new options for patients with actionable mutations, but they also add weight to a new way of thinking about cancer and how drugs are approved. “The bottom line is that we’re learning that the original way of classifying cancers — by the site from which they originated — is not really the way the cancers are driven biologically,” said Dr Kurzrock. “That means there are going to be subsets of patients in multiple different tumors that may have a genomic defect in common and can use the same drug.”

Disclosure: Some of the authors of the original Nature paper disclosed financial relationships with the pharmaceutical industry and with industry trade groups. For a full list of disclosures, please refer to the original article.


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