New Trial Shows PD-1 Inhibitor Dostarlimab Induces Complete Tumor Clearance in dMMR Cancers

In a groundbreaking update presented at the 2025 American Association for Cancer Research (AACR) Annual Meeting, researchers have reported that the PD-1 inhibitor dostarlimab-gxly resulted in complete tumor clearance in patients with locally advanced, mismatch repair-deficient (dMMR) cancers, thus eliminating the immediate need for surgery. This revelation is based on preliminary results of a phase II trial that included 103 patients suffering from stage II to III resectable dMMR cancers. The trial's lead author, Andrea Cercek, MD, of Memorial Sloan Kettering Cancer Center, has noted the importance of these findings not only for improving patient outcomes but also for potentially redefining treatment pathways for various cancer types. In the trial, patients were grouped into two cohorts: one consisting of 49 patients with rectal cancer and another 54 with nonrectal cancers, such as gastroesophageal and genitourinary cancers. Remarkably, 100% of the patients in the rectal cancer cohort experienced a complete clinical response following the six-month course of dostarlimab. Furthermore, 65% of nonrectal patients also exhibited complete clinical responses. This signifies a critical step in immunotherapy's capability to provide successful outcomes in patients who otherwise might face invasive surgical procedures. Dr. Cercek emphasized the impact of these results on the patients' quality of life, stating, 'It's likely they do not need surgery or radiation if treated first with immunotherapy for a sufficient amount of time.' Given that surgical interventions can pose significant risks, the ability to avoid such procedures is a considerable advancement in cancer treatment. The study also highlights that lower levels of circulating tumor DNA (ctDNA) during therapy correlate with a higher likelihood of complete tumor clearance. The results signify not only a potential shift in the treatment landscape for dMMR cancers but also extend the conversation about the role of immunotherapy in broader settings. Researchers, including Dr. Luis A. Diaz, Jr., have suggested that there is ample opportunity to apply these findings to other cancer types beyond dMMR tumors, paving the way for enhanced therapy strategies that preserve organ function and improve overall survivability. However, the research does come with certain caveats. While the results appear immensely promising, they need deeper investigation and further trials to validate the findings across broader patient demographics, including those with less favorable tumor responses. Many questions remain regarding the long-term effects and the optimal treatment duration using dostarlimab. These considerations are crucial in fully understanding the broad implications of this innovative approach in oncology. In examining the funding sources for the study and the authors' potential conflicts of interest, it's essential to maintain a balanced perspective. The research was supported by organizations like the National Institutes of Health and GSK, and some authors have financial ties to pharmaceutical companies, which may influence interpretations of the results. Nevertheless, the transparency regarding funding and affiliations appears to be adequately disclosed, mitigating concerns around these relationships. In conclusion, the emerging data from this trial could serve as a foundational step towards changing standard-of-care protocols for dMMR cancers, emphasizing the role of immunotherapy and potentially reshaping surgical practices in oncology.