NEOADJUVANT immunotherapy using PD-1 blockade has demonstrated the potential to eliminate the need for surgery in patients with early-stage mismatch repair-deficient (dMMR) cancers, according to groundbreaking data presented at the AACR Annual Meeting 2025. The trial results showed that dostarlimab treatment led to complete tumor clearance in a significant proportion of patients, marking a pivotal moment in the treatment of localized dMMR tumors.
The phase II study, led by Dr. Andrea Cercek of Memorial Sloan Kettering Cancer Center, evaluated dostarlimab monotherapy in 103 patients with resectable stage 2-3 dMMR cancers. The first cohort included 49 patients with rectal cancer, and the second cohort involved 54 patients with other solid tumors including gastroesophageal, hepatobiliary, genitourinary, and gynecologic cancers. Patients received dostarlimab for six months and were monitored for clinical complete response, with the option to avoid surgery if a full response was observed.
All 49 patients with rectal cancer achieved a complete clinical response. In the non-rectal cancer cohort, 65% (35 of 54) had a complete response, extending the promising results of immunotherapy beyond colorectal cancer. Of the 84 patients who achieved a complete response, 82 opted out of surgery.
Importantly, early reductions in circulating tumor DNA (ctDNA) correlated with greater likelihood of complete response, providing a potential biomarker for treatment monitoring. Long-term follow-up in the rectal cancer group revealed that 92% of patients remained disease-free at two years, and some responses have lasted up to five years.
Dr. Cercek emphasized the significance of avoiding surgery for patients with tumors in anatomically complex or sensitive areas such as the rectum, stomach, or pancreas, where surgical morbidity is high. This approach not only preserves organ function but also improves quality of life.
As the trial expands, researchers are investigating the tumor microenvironment in cancers with lower response rates, such as prostate and gastroesophageal tumors, with the goal of broadening the applicability of this strategy.
“This trial sets a foundation for reshaping early-stage cancer care,” said senior author Dr. Luis Diaz Jr., highlighting the potential for neoadjuvant immunotherapy to enhance outcomes and reduce surgical intervention.
Reference:
Cercek A, Foote M, Diaz LA Jr. Neoadjuvant PD-1 Blockade in Early-stage Mismatch Repair-deficient Cancers Can Eliminate the Need for Surgery Regardless of Tumor Type. 2025. Available at: https://aacr.ent.box.com/s/xpg9xua2oxko5uixv0sxtsb4hj8dhjdk. Last accessed: 1 May 2025.
