Recent FDA Announcements Herald Advances in Personalized Approaches Against Cancer

While we’ve known for decades that genetic mutations fuel cancer development and progression, only recently have doctors been able to begin translating that insight into improved treatment approaches and clinical benefits for patients. Since November, the U.S. Food and Drug Administration (FDA) has authorized the use of two tumor-profiling tools—both relying on next-generation genome sequencing—that should help spur even more advances in this area.

On December 1, 2017, the FDA approved the use of FoundationOne’s CDx genomic test (F1CDx), which enables doctors to determine if patients’ tumors possess any mutations among 324 clinically relevant genes. The test can also detect abnormal expression of non-mutated genes. In this way, F1CDx can serve as a companion diagnostic tool that guides doctors’ treatment decisions for their patients.

For example, if a doctor finds that a patient’s lung tumor has a mutated version of EGFR (epidermal growth factor receptor), it suggests that an FDA-approved targeted therapy such as erlotinib (Tarceva®) or osimertinib (Tarisso®) might be effective. Similarly, a breast cancer patient whose tumor overexpresses HER2 (human epidermal growth factor receptor 2) would likely be a good candidate for treatment with the HER2-targeting antibody trastuzumab (Herceptin®). In all, F1CDx can help pair patients with five different cancer types—lung, breast, melanoma, colorectal, and ovarian—with 15 different FDA-approved therapies.

Another significant aspect of F1CDx is its ability to determine if a tumor’s genome is characterized by microsatellite instability (MSI-hi). In May, a checkpoint immunotherapy—pembrolizumab (Keytruda®)—became the first treatment of any type to be approved for patients with tumors that possessed an unstable, MSI-hi genome, no matter where those tumors are located. Another checkpoint immunotherapy—nivolumab (Opdivo®)—is approved for colorectal cancer patients with MSI-hi tumors.

Furthermore, F1CDx can quantify a tumor’s mutational burden—essentially tell the doctor how many mutations it has overall. When treating patients with immunotherapy, it’s been shown that patients whose tumors are heavily mutated are much more likely to respond successfully to checkpoint immunotherapy. In addition to pembrolizumab and nivolumab, four other checkpoint immunotherapies—ipilimumab (Yervoy®), atezolizumab (Tecentriq®), avelumab (Bavencio®), durvalumab (Imfiniz®)—have been approved for patients with several types of advanced, metastatic cancers.

On November 15, 2017, the FDA authorized the use of Memorial Sloan Kettering Cancer Center’s MSK-IMPACT^TM, which also provides doctors with the ability to characterize the mutations that a patient’s tumor possesses. (In this case, MSK-IMPACT analyzes 468 different cancer-associated mutations or alterations, compared to F1CDx’s 324.)

Currently, MSK-IMPACT is only available for use at Memorial Sloan Kettering Cancer Center; however, the FDA has also taken steps to facilitate the development of additional, similar tools elsewhere. They announced “a new, streamlined regulatory process” that aims to make it easier, in terms of both time and cost, for other hospitals and medical institutions to develop their own tools to aid doctors and patients.

In addition to pairing patients with the currently approved treatments most likely to help them, these two tumor-profiling tools will aid investigations into new treatments that are being evaluated in clinical trials.