ArticleThe oncologist2025
First-line PD-1 +/- CTLA-4 blockade in patients with deficient mismatch repair and/or microsatellite instability-high metastatic colorectal cancer.
Article in The oncologist, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Mucinous histology and resistance to immune checkpoint blockade in patients with microsatellite instability-high metastatic colorectal cancer.The oncologist · 2026Article
- Advances in neoadjuvant immunotherapy for non-small cell lung cancer.Frontiers in immunology · 2026Review
- Targeting tumour-infiltrating B cells: mechanisms and advances in cancer therapy.Cell death & disease · 2025Review
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21 authors.
Funding
Abstract
backgroundPatients with deficient mismatch repair (dMMR) and/or microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) show marked sensitivity to immune checkpoint inhibitors (ICIs). Dual PD-1/CTLA-4 blockade with nivolumab and ipilimumab showed superior progression-free survival (PFS) over chemotherapy and anti-PD-1 monotherapy, but data on treatment-naïve patients is not available yet.
methodsThis international multicenter study included patients with dMMR/MSI-H mCRC receiving either chemotherapy with or without biologics, or anti-PD-1 monotherapy, or dual PD-1/CTLA-4 blockade as a first-line treatment. Data were adjusted using inverse probability of treatment weighting (IPTW) to account for baseline imbalances. IPTW-adjusted survival and subgroup analyses were conducted.
resultsAmong 711 patients, 51.2% received chemotherapy with or without biologics, 37.1% anti-PD-1 monotherapy, and 11.7% dual checkpoint blockade. Anti-CTLA-4 combination therapy significantly improved PFS (HR: 0.14; P < .001) and OS (HR: 0.13; P < .001) vs chemotherapy. In first-line IPTW-adjusted analyses (median follow-up: 29.2 months), dual blockade showed superior PFS over PD-1 monotherapy (HR: 0.58, 95% CI, 0.35-0.97, P = .037), with a favorable OS trend (HR: 0.61, 95% CI, 0.33-1.14, P = .12), and higher objective response rate (ORR) (71.5% vs 55.5%; OR: 1.15; 95% CI, 1.03-1.29; P = .016) and disease control rate (DCR) (93.7% vs 75.8%; OR, 1.18; 95% CI, 1.08-1.28; P < .001). Subgroup analyses suggested greater benefit in patients with left-sided and BRAF mutated tumors, while those with right-sided BRAF wild-type status showed no incremental benefit from dual ICI. Toxicity profile was manageable for both ICI regimen, with grade 3 or 4 immune-related adverse events registered in 11.9% and 15.7% cases in anti-PD-1 monotherapy and anti-CTLA-4 combination groups, respectively.
conclusionsFirst-line dual PD-1/CTLA-4 blockade demonstrated superior efficacy over anti-PD-1 monotherapy in dMMR/MSI-H mCRC regardless of clinical variables. Compared to previous published data across treatment lines, the prognostic impact of several clinical features does not seem to be retained in patients treated upfront with ICIs combination.
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