Multicenter phase 2 trial of afatinib plus bevacizumab after osimertinib resistance in advanced EGFR-mutant non-small cell lung cancer

Many studies of EGFR-mutated advanced non-small cell lung cancer (aNSCLC) showed synergy of EGFR-TKIs and VEGFR inhibitors. The multicenter phase 2 ABCD-study in Japan evaluated the combination of afatinib and bevacizumab for EGFR-mutated aNSCLC after development of osimertinib resistance. Response was seen in 17.9% and disease control in 78.6%, with a median duration of response of 9.0 months (range 4.2-22.3). There was no response in patients with T790M- mutation or EGFR downstreaming signaling mutations, BRAF, KRAS, or PI3K mutations, but there was response in one of six C797S patients (17%), 5 of 13 (38%) of T790M-negative patients, and radiographic response in 3 of 9 patients (33%) with uncommon EGFR mutations. The most common grade ≥ 3 adverse events were hypertension (29% of patients), proteinuria (7%), and diarrhea (7%). The authors conclude that after development of osimertinib resistance selected patients could obtain clinical benefit from afatinib plus bevacizumab.