ESMO gastrointestinal oncology · 2026
Predictive biomarkers for cetuximab-based rechallenge therapy in metastatic colorectal cancer: a pooled analysis of the CAVE and CAVE-2 GOIM studies.
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Ciardiello D, Martini G, Pietrantonio F, Avallone A, Pisconti S, Santabarbara G, Latiano T P, Tortora G, Sartore-Bianchi A, Cremolini C, Messina M, Zampino M G, Foltran L, Pinto C, Zaniboni A, Antonuzzo L, Normanno N, Berardi R, Cogoni A, Lotesoriere C, Bordonaro R, Boscolo Bielo L, Curigliano G, Manca P, Leone A G, De Stefano A, Nisi C, Rossini D, Salvatore L, Maiello E, Siena S, Troiani T, De Vita F, Fazio N, Martinelli E, Ciardiello F, Napolitano S
Аннотация
BACKGROUND: Anti-epidermal growth factor receptor (EGFR) therapy is a therapeutic option in patients with molecularly selected metastatic colorectal cancer (mCRC). However, the identification of predictive factors represents an unmet need.
PATIENTS AND METHODS: We conducted a pooled analysis of individual patient data from the CAVE-GOIM (NCT04561336) and CAVE-2 GOIM (NCT05291156) studies to investigate the impact of several clinical variables on rechallenge with cetuximab with and without avelumab in circulating tumor DNA RAS/BRAF/EGFR-extracellular domain wild-type mCRC.
RESULTS: Overall, 180 patients met the eligibility criteria: 136 received cetuximab-avelumab and 44 cetuximab. In patients receiving cetuximab monotherapy, median progression-free survival (mPFS) was 4.80 months [95% confidence interval (CI) 3.90-5.90] and median overall survival (mOS) 12.9 months (95% CI 11.1-not evaluable). Cetuximab activity was retained regardless of clinical factors. Patients treated with cetuximab-avelumab showed an mPFS of 5.00 months (95% CI 4.30-5.90) and mOS of 15.7 months (95% CI 13.0-19.9). In univariable analysis, a shorter progression-free survival was observed in patients with liver involvement [hazard ratio (HR) 2.19, 95% CI 1.51-3.20, P < 0.001] and anti-EGFR-free interval ≤16 months (HR 1.62, 95% CI 1.13-2.31, P < 0.008). Both variables retained statistical significance in multivariable analysis. In univariable analysis, lower overall survival was observed among patients treated with cetuximab-avelumab with >3 metastatic sites (HR 1.79, 95% CI 1.16-2.77, P < 0.009) and liver (HR 1.82, 95% CI 1.15-2.88, P < 0.011) and peritoneal metastases (HR 1.9, 95% CI 1.23-2.93, P < 0.004). In multivariable analysis, only liver and peritoneal metastases maintained statistical significance.
CONCLUSIONS: Single-agent cetuximab activity is not influenced by clinical factors. In cetuximab-avelumab therapy, the absence of liver metastases and longer anti-EGFR-free interval might represent potential biomarkers.
PATIENTS AND METHODS: We conducted a pooled analysis of individual patient data from the CAVE-GOIM (NCT04561336) and CAVE-2 GOIM (NCT05291156) studies to investigate the impact of several clinical variables on rechallenge with cetuximab with and without avelumab in circulating tumor DNA RAS/BRAF/EGFR-extracellular domain wild-type mCRC.
RESULTS: Overall, 180 patients met the eligibility criteria: 136 received cetuximab-avelumab and 44 cetuximab. In patients receiving cetuximab monotherapy, median progression-free survival (mPFS) was 4.80 months [95% confidence interval (CI) 3.90-5.90] and median overall survival (mOS) 12.9 months (95% CI 11.1-not evaluable). Cetuximab activity was retained regardless of clinical factors. Patients treated with cetuximab-avelumab showed an mPFS of 5.00 months (95% CI 4.30-5.90) and mOS of 15.7 months (95% CI 13.0-19.9). In univariable analysis, a shorter progression-free survival was observed in patients with liver involvement [hazard ratio (HR) 2.19, 95% CI 1.51-3.20, P < 0.001] and anti-EGFR-free interval ≤16 months (HR 1.62, 95% CI 1.13-2.31, P < 0.008). Both variables retained statistical significance in multivariable analysis. In univariable analysis, lower overall survival was observed among patients treated with cetuximab-avelumab with >3 metastatic sites (HR 1.79, 95% CI 1.16-2.77, P < 0.009) and liver (HR 1.82, 95% CI 1.15-2.88, P < 0.011) and peritoneal metastases (HR 1.9, 95% CI 1.23-2.93, P < 0.004). In multivariable analysis, only liver and peritoneal metastases maintained statistical significance.
CONCLUSIONS: Single-agent cetuximab activity is not influenced by clinical factors. In cetuximab-avelumab therapy, the absence of liver metastases and longer anti-EGFR-free interval might represent potential biomarkers.