The US Food and Drug Administration (FDA) recently granted the accelerated approval of Keytruda (pembrolizumab), marking the first approval of a cancer treatment based on a tumor’s genetic markers rather than the location from which the tumor originated [1]. Traditionally, cancers and their treatments are defined by the affected body part. Some genetic mutations, however, can result in tumor growth in multiple organs, making numerous mutations common in multiple cancer types. Keytruda is for adults and children with advanced tumors that have specific genetic changes - either high levels of microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR) - that continue to grow despite prior therapies [2]. MSI-H and dMMR tumors contain abnormalities that affect proper DNA repair within cells. Tumors with these genetic markers are commonly found in colorectal, endometrial and gastrointestinal cancers, but can also appear in cancers in the prostate, bladder, breast, thyroid gland and other places around the body [3].
“Tumor-agnostic” therapies such as Keytruda allow for doctors and researchers to approach the disease from a different angle. Dr. Steven Lemery, the FDA’s lead medical officer for regulatory approvals said that tumor-agnostic therapies have “defined a new disease entity” [3]. In regards to Keytruda specifically, Dr. Lemery suggests the approval can allow patients with MSI-H/dMMR tumors to benefit “regardless of whether they have colorectal cancer, endometrial cancer, gastric cancer, pancreatic cancer, or any other tumor type” [3].
A downside of the tissue-agnostic approach may be the inability to use powerful drug combinations [3]. Treatments that target a specific genetic mutation may perform differently against varying tumor types [3]. These diagnostic developments require additional clinical testing among tumor types in order to track variations in result in locations throughout the body [3]. Despite this, additional tissue-agnostic drugs have been progressing through clinical trials. Second to Keytruda, the experimental drug Larotrectinib will likely become approved by 2018, paving the way for additional tissue-independent treatments to reach patients around the country [4]. Alice Shaw, director of thoracic oncology at Massachusetts General Hospital in Boston says that these approvals are “a sign of the times…the molecular biology of the tumor is really leading the way over the tissue of origin” [5].
References:
“FDA approves first cancer treatment for any solid tumor with a specific genetic feature,” FDA, May 23 2017.https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm560167.htm
Simon, Stacy. FDA Approves Keytruda (Pembrolizumab) for Any Tumor with Specific Genetic Change, American Cancer Society, May 24 2017. https://www.cancer.org/latest-news/fda-approves-keytruda-pembrolizumab-for-any-tumor-with-specific-genetic-change.html
O’Rourke, Kate M.“'Tumor-Agnostic' Drug Approvals a Paradigm Shift in Cancer, With Many Unanswered Questions,” Medscape, June 19 2017. http://www.medscape.com/viewarticle/881609
Cortez, Michelle. “Cancer drug targeting rare mutation works across tumor types,” Bloomberg, June 3 2017. https://www.bloomberg.com/news/articles/2017-06-03/cancer-drug-targeting-rare-mutation-works-across-tumor-types
Garber, Ken. “In a major shift, cancer drugs go ‘tissue-agnostic’”, Science, June 16 2017. http://science.sciencemag.org/content/356/6343/1111