Two Key Trials Redefine Immunotherapy's Role: Zero Relapses in Bowel Cancer and Sustained PFS Benefit in Endometrial Cancer

Two major clinical trial updates are reshaping first-line treatment approaches for mismatch repair-deficient (dMMR) cancers. The NEOPRISM-CRC trial explores whether a short course of pembrolizumab before surgery can replace post-operative chemotherapy in bowel cancer, while the NRG-GY018 trial tests adding pembrolizumab to standard chemotherapy in advanced endometrial cancer. Their latest results provide durable evidence that immunotherapy can achieve long-term cancer control, and in some cases, eliminate the need for conventional chemotherapy altogether.

NEOPRISM-CRC: A short immunotherapy course before surgery yields zero relapses

The NEOPRISM-CRC trial is a phase II study evaluating neoadjuvant pembrolizumab in patients with high-risk stage 2 or stage 3 dMMR/MSI-high colorectal cancer . An initial cohort of 32 patients received just three cycles (nine weeks) of pembrolizumab before undergoing surgery .

Pathologic responses were high from the start. Earlier results showed that 59% of patients had a complete pathologic response (pCR)—meaning no viable tumor was found at the time of surgery—and 78% achieved a major pathologic response (MPR). The six-month disease-free survival rate was 100% .

The headline durability update, presented at the AACR Annual Meeting in April 2026, is zero relapses. After nearly three years of follow-up, none of the patients who received this pre-operative immunotherapy have experienced a cancer recurrence . This durable disease-free interval directly challenges the conventional sequence of surgery followed by months of adjuvant chemotherapy.

The findings suggest that for carefully selected patients—those with dMMR or MSI-high, high-risk stage 2 or 3 colorectal cancer—a short, well-tolerated immunotherapy course before surgery may be sufficient to produce long-lasting remission. The trial provides compelling evidence that a neoadjuvant checkpoint blockade could allow some patients to avoid perioperative chemotherapy entirely .

NRG-GY018: Adding pembrolizumab to chemotherapy delivers a large progression-free survival benefit

The phase III NRG-GY018 trial evaluated pembrolizumab plus carboplatin/paclitaxel versus placebo plus chemotherapy as first-line treatment for advanced or recurrent endometrial cancer. Outcomes were analyzed by mismatch repair status .

Progression-free survival (PFS) benefit, particularly in dMMR disease.

• dMMR cohort (12-month analysis): Kaplan-Meier estimates of PFS were 74% for pembrolizumab plus chemotherapy versus 38% for placebo plus chemotherapy. This corresponds to a hazard ratio (HR) of 0.30 for progression or death, representing a 70% relative reduction in risk (P<0.001) .
• pMMR cohort: Median PFS was 13.1 months with pembrolizumab compared to 8.7 months with placebo (HR 0.54; P<0.001), a 46% relative risk reduction .

These results led the FDA to approve pembrolizumab with carboplatin and paclitaxel, followed by single-agent pembrolizumab, on June 17, 2024, for adults with primary advanced or recurrent endometrial carcinoma. The approval was based on PFS as the primary efficacy measure .

Overall survival data are maturing. Initial overall survival (OS) analyses were immature, but hazard ratios favored the pembrolizumab arm (dMMR: 0.55; pMMR: 0.79) . An updated analysis with prolonged follow-up, reported in May 2026, demonstrated a sustained numerical benefit in overall survival for patients receiving pembrolizumab plus chemotherapy—even though a large proportion of initial placebo-treated patients crossed over to receive immunotherapy after progression . While formal statistical significance for OS has not been established in the available sources, the consistent OS trend reinforces the PFS advantage.

What the two trials mean together for immunotherapy's expanding role

The NEOPRISM-CRC and NRG-GY018 trials illustrate two distinct ways immunotherapy is changing treatment paradigms for dMMR tumors:

1. Replacing chemotherapy when possible. NEOPRISM-CRC shows that in biomarker-selected bowel cancer, a brief course of immunotherapy before surgery alone can produce durable, relapse-free outcomes. This supports a chemotherapy-sparing strategy for a well-defined patient subset.

2. Adding to chemotherapy when necessary. NRG-GY018 demonstrates that even when chemotherapy remains the backbone, immunotherapy can dramatically improve progression-free survival and show encouraging survival trends.

Together, these results strengthen the case for routine mismatch repair testing to guide treatment decisions, with the goal of delivering more personalized, effective, and potentially less toxic regimens. The NEOPRISM-CRC relapses durability signal is especially striking—it suggests that for some patients, a short neoadjuvant immunotherapy course may do more than simply delay chemotherapy; it may make it obsolete.