Neoadjuvant Immunotherapy in Patients With Localized dMMR Colorectal Cancer

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Investigators discovered that PD-1 inhibition prior to surgery may be effective for patients with localized mismatch repair–deficient or microsatellite instability–high (dMMR/MSI-H) colorectal cancer, according to a study published by Xiao et al in JNCCN–Journal of the National Comprehensive Cancer Network.

Study Methods and Results

The investigators anticipated that PD-1 inhibitors could be at least as effective for locally advanced but operable cancer as they have historically been in the treatment of metastatic dMMR/MSI-H colorectal cancer, but were surprised to find that the treatment was far more effective for this patient population.

The study included a retrospective review of 73 patients aged 18 and 75 years with confirmed dMMR/MSI-H colorectal cancer, who previously received any type of neoadjuvant PD-1 inhibitor between October 2017 and December 2021. Among the 73 patients, 66% of them (n = 48) were diagnosed with colon cancer, 24.7% (n = 18) with rectal cancer, and 9.6% (n = 7) with multiple types of colorectal cancer. Overall, 84.9% (n = 62) experienced an objective response, 23.3% (n = 17) demonstrated complete response, and 61.6% (n = 45) demonstrated partial response. The 2-year rates for tumor-specific overall survival and disease-free survival were 100% for patients who underwent surgery after PD-1 inhibition.

Nearly all of the patients involved in the study benefitted from neoadjuvant PD-1 inhibitors. In addition to the short-term effectiveness, the findings showed substantial longer survival benefits associated with neoadjuvant PD-1 inhibitors—including a low recurrence rate when compared with historic rates.


“We need to keep in mind that our final goal is to cure patients [for the] long term, not just remove the tumor at the moment,” stressed senior study author Pei-Rong Ding, MD, PhD, Professor of Surgery and Chief Surgeon in the Department of Colorectal Cancer at the Sun Yat-sen University Cancer Center. “I think care providers, especially surgeons, should refrain from scheduling immediate surgery for patients with locally advanced or even early-stage dMMR/MSI-H colorectal cancer. With such a powerful option at hand, we have the duty to offer a safer surgery with better outcomes or a nonsurgical, yet equally effective, approach for this group of patients—especially for those who might suffer from function damage or organ sacrifice after surgery.”

The study had an average follow-up time of 17.2 months, with 16 patients tracked for more than 2 years. The investigators hope to conduct further studies with even longer follow-up to confirm these results, especially following treatment cessation. They also noted that there may be more to learn about the long-term safety of this approach and possible implications for limiting or avoiding surgery entirely.

"The treatment of [localized] dMMR colorectal cancer is a highly active area of research,” explained Dustin A. Deming, MD, Associate Professor of Hematology, Medical Oncology, and Palliative Care in the Department of Medicine at the University of Wisconsin-Madison Carbone Cancer Center, as well as a member of the NCCN Guidelines Panel for Colon/Rectal/Anal Cancers, who was not involved in this study. He concluded, “This retrospective analysis highlights the potential for significant treatment responses with limited toxicities for these patients treated with immune checkpoint inhibitors. It will be exciting to see how these results, and other completed and ongoing studies, will be utilized to incorporate anti–PD-1 treatments into the standard of care for locally advanced colorectal cancers."

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