Botensilimab Plus Balstilimab Associated With Improved Survival in Refractory Microsatellite-Stable Metastatic Colorectal Cancer
Clinical Summary:
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Design/Population: This systematic comparative analysis reconstructed individual patient-level data from a phase 1 trial of botensilimab plus balstilimab and compared outcomes with four pivotal studies (SUNLIGHT, FRESCO-2, RECOURSE, and CORRECT) in patients with refractory microsatellite-stable metastatic colorectal cancer (mCRC).
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Key Outcomes: Botensilimab plus balstilimab was associated with longer overall survival than currently available later-line therapies. Progression-free survival also compared favorably with most standard treatments, although trifluridine-tipiracil plus bevacizumab demonstrated superior progression-free survival. The combination exhibited a distinct safety profile characterized primarily by fatigue and diarrhea.
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Clinical Relevance: These findings suggest that dual immune checkpoint blockade with botensilimab plus balstilimab may offer meaningful survival benefit in refractory microsatellite-stable mCRC and support prospective randomized evaluation against current standards of care.
Results from a systematic comparative analysis suggested that botensilimab plus balstilimab may improve overall survival compared with currently available later-line therapies for patients with refractory microsatellite-stable metastatic colorectal cancer (mCRC).
“Over the past year, many early phase trials evaluating novel compounds have been designed [and] promising results have been reported with the combination of botensilimab [plus] balstilimab,” stated Elisabetta Bengala, MD, Regina Elena National Cancer Institute, Rome, Italy, and coauthors. “We carried out a systematic review of clinical trials of unselected patients with refractory mCRC, with the aim of comparing new treatment strategies with the current standard of care.”
Investigators reconstructed individual patient-level overall survival (OS) and progression-free survival (PFS) data from Kaplan-Meier curves of a phase 1 trial evaluating botensilimab plus balstilimab and four pivotal studies of later-line therapy (SUNLIGHT, FRESCO-2, RECOURSE, and CORRECT). The primary end point was OS, with PFS and safety assessed as secondary end points.
Botensilimab plus balstilimab was associated with longer OS than trifluridine-tipiracil plus bevacizumab (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.44 to 0.89), fruquintinib (HR, 0.38), regorafenib (HR, 0.32), and trifluridine-tipiracil monotherapy (HR, 0.37).
The combination also demonstrated longer PFS than most comparator regimens. However, trifluridine-tipiracil plus bevacizumab was associated with superior PFS compared with botensilimab plus balstilimab (HR, 0.46).
The safety profile of botensilimab plus balstilimab differed from that of currently available cytotoxic and targeted therapies. Fatigue and diarrhea were the most frequently reported adverse events with dual checkpoint blockade, whereas comparator regimens were more commonly associated with hematologic toxicities, nausea, hypertension, and dermatologic adverse events.
“By comparing current standard-of-care treatments with a potential novel therapy in refractory mCRC, this review underscores existing gaps and highlights future research priorities while awaiting randomized data,” concluded Dr Bengala et al.
Source:
Bengala E, Santini D, Picone V. Refractory microsatellite-stable metastatic colorectal cancer: A comparison between botensilimab + balstilimab and current standard of care. IOTECH. Published online: November 27, 2025. doi: 10.1016/j.iotech.2025.101558
