The latest approval of a cancer drug by the US Food and Drug Administration (FDA) changes the paradigm of cancer treatment — the new indication specifies a genetic defect without any mention of tumor types. It allows the drug to be used in any cancer that harbors the specified genetic defect, wherever the tumor appears in the body.
What: Historically, the US Food and Drug Administration (FDA) has approved cancer treatments based on where in the body the cancer started — for example, prostate or breast cancers. For the first time, the FDA approved a drug based on a tumor’s biomarker without regard to the tumor’s original location.
Details: The new approval is for the immunotherapy pembrolizumab (Keytruda, Merck & Co), which is already approved for use in several different tumor types, including melanoma and lung cancer. But this latest approval covers the use of pembrolizumab in tumors that have microsatellite instability-high (MSI-H) or are mismatch repair deficient (dMMR). These defects are found most commonly in colorectal, endometrial, and gastrointestinal cancers but also less commonly appear in cancers arising in the breast, prostate, bladder, thyroid gland, and other places, the agency notes.
Microsatellite instability & immunotherapy: It’s not just colorectal cancer: The results from that trial showed that patients with colorectal cancer with normal DNA repair (microsatellite stable) had zero response to pembrolizumab, whereas those with MSI and deficient DNA repair had a 50% response rate, she said. In addition, about 20% had stable disease. This is much higher than has been seen with immunotherapy in other tumor types, where fewer than 20% patients respond. But the trial also included patients with any solid tumor and MSI, and these patients also showed the 50% response rate and 20% stable disease results.
Downsides: Common side effects of pembrolizumab include fatigue, itchiness, diarrhea, decreased appetite, rash, fever, cough, dyspnea, musculoskeletal pain, constipation, and nausea. The drugs can also cause serious immune-mediated side effects, including lung, liver, kidney, or colon inflammation, endocrine problems.
Action point: All patients with advanced cancer who have had at least one standard therapy should be tested to see if their tumor harbors these genetic defects.
I’m Dr. Michael Hunter.