Skin Toxicity as Predictor of Survival in Refractory Patients with <i>RAS</i> Wild-Type Metastatic Colorectal Cancer Treated with Cetuximab and Avelumab (CAVE) as Rechallenge Strategy

Skin Toxicity as Predictor of Survival in Refractory Patients with <i>RAS</i> Wild-Type Metastatic Colorectal Cancer Treated with Cetuximab and Avelumab (CAVE) as Rechallenge Strategy

The single-arm phase II CAVE mCRC trial evaluated the combination of cetuximab plus avelumab as rechallenge strategy in <i>RAS</i> wild-type (WT) metastatic colorectal cancer (mCRC) patients, with clinical response to first-line anti-EGFR-based chemotherapy, who progressed and received a...

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Main Authors: Davide Ciardiello, Vincenzo Famiglietti, Stefania Napolitano, Lucia Esposito, Nicola Normanno, Antonio Avallone, Tiziana Latiano, Evaristo Maiello, Filippo Pietrantonio, Chiara Cremolini, Giuseppe Santabarbara, Carmine Pinto, Teresa Troiani, Erika Martinelli, Fortunato Ciardiello, Giulia Martini
Format: article
Language:EN
Published: MDPI AG 2021
Subjects:
rechallenge anti-EGFR
immunotherapy
skin toxicity
mCRC
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Online Access:https://doaj.org/article/644e2914914c48e9b39e0f6cb9eac8c7
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Summary:The single-arm phase II CAVE mCRC trial evaluated the combination of cetuximab plus avelumab as rechallenge strategy in <i>RAS</i> 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; <i>p</i> = 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; <i>p</i> = 0.004). Grade 2–3 ST (HR, 0.51; CI 95%, 0.29–0.89; <i>p</i> = 0.019) and <i>RAS/BRAF/EGFR</i> WT circulating tumor DNA (ctDNA) (HR, 0.50; CI 95%, 0.27–0.9; <i>p</i> = 0.019) had a statistically significant effect on OS at univariate analysis. At the multivariate analysis, <i>RAS/BRAF/EGFR</i> WT ctDNA status maintained statistical significance (HR, 0.49; CI 95%, 0.27–0.9; <i>p</i> = 0.023), whereas there was a trend towards ST grade 2–3 (HR, 0.54; CI 95%, 0.29–1.01; <i>p</i> = 0.054). Skin toxicity is a promising biomarker to identify patients with mCRC that could benefit of anti-EGFR rechallenge.

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