Erlotinib plus bevacizumab in EGFR-amplified metastatic solid tumors: results from the KOSMOS I, II study of molecular profiling-guided therapy in advanced cancers

초록

PurposeEpidermal growth factor receptor (EGFR) amplification remains a controversial therapeutic biomarker. We report outcomes of erlotinib plus bevacizumab (E + B) in patients with EGFR-amplified metastatic solid tumors.MethodsPatients with metastatic solid cancer who had progressed after standard therapies and were treated with E + B based on central molecular tumor board recommendations in the KOSMOS trial were included. Only those with an EGFR copy number >= 3 were selected. The primary endpoint was the clinical benefit rate (CBR), while secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety.ResultsBetween February 2021 and April 2024, 25 patients were treated with E + B (median EGFR copy 8.9; range, 3-76). Six tumor types were included, with colorectal cancer being the most prevalent (N = 14), followed by glioblastoma (N = 5), and other types (N = 6). Overall, four partial responses (PR) and seven cases of stable disease (SD) lasting over 16 weeks were observed, resulting in a CBR of 44.0% and ORR of 16%. The median PFS was 3.7 months (95% confidence interval [CI]: 1.7-4.6), whereas the median OS was 7.9 months (95% CI: 6.5 to not estimable). Six patients experienced one or more grade 3 adverse events related to E + B, including hypertension and mucositis.ConclusionThe E + B combination showed modest anti-tumor activity in patients with heavily pretreated EGFR-amplified solid cancers. While NGS may help identify new applications for existing drugs, additional investigations are warranted to validate the efficacy and benefit of E + B in this population.

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