A landmark study led in part by physician-researchers from Memorial Sloan Kettering is giving new hope to some people with metastatic colorectal cancer. In a recent issue of the New England Journal of Medicine, results from the phase III study — Keynote 177 — provided further proof that the immunotherapy drug pembrolizumab can improve disease progression in patients with unresectable and microsatellite instability–high (MSI-H)/mismatch repair deficient (dMMR) metastatic colorectal cancer when used as frontline treatment.
In June, pembrolizumab received FDA breakthrough designation for treatment in this subset of patients. Roughly 5 percent of people with metastatic colorectal cancer have MSI-H/dMMR disease. In cancer, microsatellite instability means there are higher numbers of mutations within individual cancer cells, creating a more unstable environment which is often less responsive to traditional chemotherapy.
“Historically, people with mismatch repair deficient metastatic colorectal cancer faced much poorer outcomes, so the results are significant,” said Luis A. Diaz, MD, head of the division of Solid Tumor Oncology at MSK, and one of the study’s lead authors. “Similar to other studies of immunotherapy in mismatch repair deficient tumors, responses were durable often lasting two years or longer,” added Dr. Diaz.
Zsofia Stadler, MD, medical oncologist at MSK added, “Previously, patients with this cancer type were offered chemotherapy and, in some cases, a targeted therapy as upfront treatment. The long-awaited results from this trial represent a paradigm shift.”
Using this new approach, patients also made fewer visits to the clinic and experienced more manageable side effects versus the standard treatment.
However, as physician-researchers have witnessed in other studies of different immunotherapy treatments, the drug’s effectiveness was not seen in every study participant. Approximately 48 percent of patients didn’t respond and experienced disease progression.
Colorectal cancer is the third most common cancer in the United States and the second most deadly. Almost 1.8 million cases of colorectal cancer are diagnosed globally each year, with an estimated 900,000 deaths caused by the disease. In the United States alone, an estimated 150,000 new cases were diagnosed in 2019, with nearly 52,000 deaths reported.