We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Skin Toxicity as Predictor of Survival in Refractory Patients with RAS Wild-Type Metastatic Colorectal Cancer Treated with Cetuximab and Avelumab (CAVE) as Rechallenge Strategy.
- Authors
Ciardiello, Davide; Famiglietti, Vincenzo; Napolitano, Stefania; Esposito, Lucia; Normanno, Nicola; Avallone, Antonio; Latiano, Tiziana; Maiello, Evaristo; Pietrantonio, Filippo; Cremolini, Chiara; Santabarbara, Giuseppe; Pinto, Carmine; Troiani, Teresa; Martinelli, Erika; Ciardiello, Fortunato; Martini, Giulia
- Abstract
Simple Summary: Anti-EGFR-related skin toxicity has been described as a predictive biomarker of response in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC). With the CAVE mCRC trial we previously provided the first evidence of the activity of cetuximab plus avelumab as rechallenge treatment in pretreated chemo-refractory RAS WT mCRC. Nowadays, skin toxicity remains the only confirmed clinical biomarker of response to anti-EGFR treatment in mCRC. The role of skin toxicity has not yet been explored in a rechallenge setting. In this paper we provide a post-hoc analysis of the CAVE mCRC trial that investigated the role of skin toxicity as a predictive biomarker of activity of cetuximab plus avelumab treatment and its correlation with different clinico-molecular variables on survival at the univariate and multivariate levels. High-grade skin toxicity, together to the circulating tumor DNA RAS/BRAF/EGFR wild-type status were the only variables with an impact on PFS and OS. The single-arm phase II CAVE mCRC trial evaluated the combination of cetuximab plus avelumab as rechallenge strategy in RAS wild-type (WT) metastatic colorectal cancer (mCRC) patients, with clinical response to first-line anti-EGFR-based chemotherapy, who progressed and received a subsequent line of therapy. The correlation of skin toxicity (ST) and different clinico-molecular variables with overall survival (OS), progression-free survival (PFS) and response rate (RR) was assessed at univariate and multivariate analysis. A total of 33/77 (42.9%) patients experienced grade 2–3 ST and displayed median OS (mOS) of 17.8 months (CI 95%, 14.9–20.6); whereas 44/77 (57.1%) patients with grade 0–1 ST exhibited mOS of 8.2 months (CI 95%, 5.5–10.9), (hazard ratio (HR), 0.51; CI 95%, 0.29–0.89; p = 0.019). Median PFS (mPFS) was 4.6 months (CI 95%, 3.4–5.7) in patients with grade 2–3 ST, compared to patients with grade 0–1 ST with mPFS of 3.4 months (CI 95%, 2.7–4.1; HR, 0.49; CI 95%, 0.3–0.8; p = 0.004). Grade 2–3 ST (HR, 0.51; CI 95%, 0.29–0.89; p = 0.019) and RAS/BRAF/EGFR WT circulating tumor DNA (ctDNA) (HR, 0.50; CI 95%, 0.27–0.9; p = 0.019) had a statistically significant effect on OS at univariate analysis. At the multivariate analysis, RAS/BRAF/EGFR WT ctDNA status maintained statistical significance (HR, 0.49; CI 95%, 0.27–0.9; p = 0.023), whereas there was a trend towards ST grade 2–3 (HR, 0.54; CI 95%, 0.29–1.01; p = 0.054). Skin toxicity is a promising biomarker to identify patients with mCRC that could benefit of anti-EGFR rechallenge.
- Subjects
BIOMARKERS; SURVIVAL; STATISTICS; CONFIDENCE intervals; ONCOGENES; EPIDERMAL growth factor receptors; MULTIVARIATE analysis; METASTASIS; MONOCLONAL antibodies; COLORECTAL cancer; TREATMENT effectiveness; DRUG eruptions; DATA analysis; DRUG toxicity
- Publication
Cancers, 2021, Vol 13, Issue 22, p5715
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers13225715