PD-L1 targeting and subclonal immune escape mediated by PD-L1 mutations in metastatic colorectal cancer.

Background: In patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC), immune checkpoint blockade is ineffective, and combinatorial approaches enhancing immunogenicity need exploration.

Methods: We treated 43 patients with predominantly microsatellite stable wild-type mCRC on a phase II trial combining chemotherapy with the epidermal growth factor receptor antibody cetuximab and the programmed cell death ligand 1 (PD-L1) antibody avelumab. We performed next-generation gene panel sequencing for mutational typing of tumors and liquid biopsy monitoring as well as digital droplet PCR to confirm individual mutations.

Evaluation of EGFR inhibitor-mediated acneiform skin toxicity within the double-blind randomized EVITA trial: A thorough gender-specific analysis using the WoMo score.

Acne-like skin reactions frequently occur in patients undergoing treatment with drugs inhibiting the epidermal growth factor receptor. Recently, the effects of vitamin K1 containing cream (Reconval K1) as prophylactic skin treatment in addition to doxycycline were explored in a double-blind randomized phase II trial (EVITA) in patients with metastatic colorectal cancer receiving cetuximab. EVITA demonstrated a trend towards less severe skin rash in Reconval K1-treated patients using the tripartite WoMo skin reaction grading score as a thorough tool for quantification of drug related skin reactions.