Disease-free survival and overall survival after neoadjuvant immunotherapy in mismatch repair-deficient colon cancer in the Netherlands: results of the single-arm, multicentre, phase 2, NICHE-2 trial.
Myriam Chalabi, Lauren D W van den Dungen, Peter G M de Gooyer et al.
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In 30 seconds
This single-arm, multicentre phase 2 trial assessed neoadjuvant ipilimumab plus nivolumab followed by surgery in previously untreated patients with resectable stage 2 or 3 mismatch repair-deficient colon cancer. Among 111 patients in the per-protocol population, median postoperative follow-up was 58·7 months. Three-year disease-free survival was 100% (97·5% CI 100-100); exploratory 5-year overall survival was also 100% (95% CI 100-100). The findings extend earlier reports of pathological response and suggest durable outcomes after this treatment, although the study had no comparator group.
Key findings
- Three-year disease-free survival was 100% (97·5% CI 100-100) among 111 per-protocol patients.
- Exploratory 5-year overall survival was 100% (95% CI 100-100) after a median enrolment-based follow-up of 60·4 months.
- After the second treatment cycle and before surgery, ctDNA clearance was observed in 80 (82%) of 97 patients with available samples.
- Postoperative minimal residual disease assessment found all patients to be ctDNA negative.
Why it matters
Durable disease-free and overall survival outcomes address an important uncertainty about neoadjuvant immune checkpoint blockade in locally advanced dMMR colon cancer. The ctDNA findings also show that clearance was common before surgery and that postoperative samples were negative in all assessed patients. Together, these results provide clinically relevant evidence for evaluating this approach in this defined population.
What to keep in mind
The trial was single-arm, so outcomes cannot be compared directly with those under alternative treatment strategies. Overall survival was an exploratory post-hoc analysis.