Nivolumab in patients with DNA mismatch repair deficient/microsatellite instability high metastatic colorectal cancer: Update from CheckMate 142.

Abstract

519 Background: Approximately 4% of metastatic colorectal cancers (mCRCs) are associated with high microsatellite instability (MSI-H), indicating a deficient DNA mismatch repair (dMMR) system. dMMR/MSI-H CRC exhibits an increased tumor neoantigen load and immune cell infiltration and is hypothesized to be targetable by immune checkpoint inhibitors. CheckMate 142 (NCT02060188) evaluates the efficacy and safety of nivolumab (nivo) in patients (pts) with dMMR/MSI-H mCRC. Methods: Pts with dMMR/MSI-H mCRC who progressed on/were intolerant to ≥1 prior line of therapy received nivo 3 mg/kg (nivo 3) every 2 weeks (Q2W). The primary endpoint was objective response rate (ORR) per investigator (INV). The secondary endpoint was ORR per independent radiology review committee (IRRC); exploratory endpoints included safety, PFS, OS, and efficacy in biomarker-defined populations. Results: Among pts treated with nivo 3 Q2W (N = 74), 84% had received ≥2 prior lines of therapy. ORRs were 31% (INV) and 27% (IRRC); disease control rates were 69% (INV) and 62% (IRRC). The median time to response was ≈2.7 mo (INV/IRRC). PFS rates at 12 mo were 48.4% (INV) and 45.6% (IRRC). The duration of response and OS medians were not yet reached; OS rates were 83.4% (6 mo) and 73.8% (12 mo). Responses were observed in pts regardless of tumor programmed death-1 ligand 1 (PD-L1) expression level or BRAF or KRAS mutation status and were observed in pts with or without a history of Lynch syndrome (Table). Grade 3–4 treatment-related adverse events (TRAEs) occurred in 20% of pts. TRAEs leading to discontinuation included acute kidney injury, increased ALT, colitis, and stomatitis (1 each). No treatment-related deaths occurred in this arm. Conclusions: Nivo showed durable responses and disease control in heavily pretreated pts with dMMR/MSI-H mCRC. Treatment was well tolerated, with no new safety signals. Clinical trial information: NCT02060188. [Table: see text]

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Affiliated Institutions

• Universitair Ziekenhuis Brussel BE
• St. Vincent's University Hospital IE
• Hospital General Universitario Gregorio Marañón ES
• University of Pittsburgh US
• Trans Tasman Radiation Oncology Group AU
• Bristol-Myers Squibb (United States) US
• Duke Medical Center US
• Allina Health US
• Fondazione Piemontese per la Ricerca sul Cancro Onlus IT
• Sorbonne Université FR
• The Royal Melbourne Hospital AU
• Istituti di Ricovero e Cura a Carattere Scientifico IT
• Hôpital Saint-Antoine FR
• The University of Texas MD Anderson Cancer Center US
• Candiolo Cancer Institute IT
• University of Southern California US
• The University of Sydney AU
• USC Norris Comprehensive Cancer Center US
• Istituto Oncologico Veneto IT

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