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Rechallenge of RAS/BRAF wildtype CRC with avelumab plus cetuximab

ESMO 2020
First results of the CAVE trial showed encouraging effectiveness of rechallenging patients with RAS wildtype metastatic colorectal cancer (mCRC) in third line with cetuximab plus avelumab.

Rechallenge strategies with anti-epidermal growth factor receptor (EGFR) drugs have been evaluated in patients with refractory RAS/BRAF wildtype mCRC after response to anti-EGFR based first-line therapy [1].

In the phase 2, single-arm CAVE mCRC trial, 77 patients with RAS wildtype mCRC at baseline were enrolled [2]. All patients were treated first-line with chemotherapy plus anti-EGFR, achieved a partial or complete response in first line, and received a second-line treatment without anti-EGFR. In third-line, patients were rechallenged with avelumab (10 mg/kg every 14 days) plus cetuximab (400 mg/m2 and subsequently 250 mg/m2 weekly) until progression of disease or unacceptable toxicity.

Median overall survival (OS) was 13.1 months; median progression-free survival (PFS) was 3.6 months. Among 77 patients evaluable for response, 1 patient experienced complete response, 5 patients partial response, and 44 patients stable disease; 27 patients progressed. Grade 3 adverse events were reported in 22% of patients, the most common being skin rash and diarrhoea. In an explorative analysis, ctDNA at treatment baseline proved to be prognostic.

  1. Cremolini C, et al. JAMA Oncol. 2019;5:343-350.
  2. Martineli E, et al. Avelumab plus cetuximab in pre-treated RAS wild type metastatic colorectal cancer patients as a rechallenge strategy: The phase II CAVE (cetuximab-avelumab) mCRC study. ESMO 2020 Virtual Meeting, abstract 397O.

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