Preoperative nivolumab plus ipilimumab appears safe and feasible for patients with early-stage colon cancer, according to researchers.
The combination produced few grade 3/4 toxicities in a phase 2 trial. It also produced pathological responses in 100% of patients with mismatch repair-deficient (dMMR) tumors and in 27% of patients with MMR-proficient (pMMR) tumors. Myriam Chalabi, MD, of the Netherlands Cancer Institute in Amsterdam, and colleagues reported these results in Nature Medicine.
The open-label, exploratory trial included 40 patients with resectable, early-stage colon adenocarcinoma, 21 of whom had dMMR tumors and 20 of whom had pMMR tumors (1 patient had both tumor types). The patients underwent surgery within 6 weeks of study enrollment.
Prior to surgery, patients received ipilimumab (1 mg/kg) on day 1 plus nivolumab (3 mg/kg) on days 1 and 15. Those with pMMR tumors also received celecoxib (200 mg) from day 1 until the day leading up to surgery. The primary endpoints were safety and feasibility. Efficacy was evaluated using histopathological response.Grade 3-4 treatment‐related adverse events (AEs) were reported in 5 patients (13%). These AEs included rash, colitis, and asymptomatic rises in laboratory parameters. Grade 3 surgery-related AEs occurred in 8 patients (20%).
“This treatment is both safe and feasible, with few treatment-related AEs and without compromising surgery,” the authors wrote.
There were 35 patients evaluable for response. Among patients with dMMR tumors, pathological responses occurred in 100% (n = 20), major pathological responses (<10% residual vital tumor) occurred in 95% (n = 19), and complete responses occurred in 60% (n = 12).
Among patients with pMMR tumors, 27% (n = 4) had a pathological response, 20% (n = 3) had a major pathological response, and 7% (n = 1) had a partial response.
The researchers acknowledged that the small sample size and short duration of postoperative follow-up were key limitations of this study, but they said this combination should be studied further.
“Neoadjuvant immunotherapy in early-stage colon cancers warrants further research and, when validated in larger studies with longer follow-up, may become a new standard of care in dMMR and possibly a subgroup of pMMR colon cancers,” the authors concluded.
This study was sponsored by the Netherlands Cancer Institute in collaboration with Bristol-Myers Squibb. Authors reported financial relationships with Bristol-Myers Squibb and many other companies.
SOURCE: Chalabi M et al. Nat Med. 2020 Apr 6. doi: 10.1038/s41591-020-0805-8.