Erlotinib plus bevacizumab in patients with metastatic solid tumors with EGFR amplification: Results from the KOSMOS-II (KOrean Precision Medicine Networking Group Study of MOlecular profiling guided therapy based on genomic alterations in advanced solid tumors, KCSG AL 22-09)

초록

Background The KOSMOS-II is an ongoing, nation-wide master observational trial designed to screen patients with metastatic solid tumors using local NGS testing and to recommend molecularly guided treatment through central virtual molecular tumor board (NCT05525858). This study reports data from patients with EGFR-amplified metastatic solid tumors treated with the combination of erlotinib and bevacizumab (E+B). Methods Metastatic solid cancer patients with no standard treatment options were selected for treatment with E+B according to MTB recommendation. The primary endpoint was the clinical benefit rate (CBR). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Results Between February 2021 and April 2024, twenty-five patients with EGFR amplification (median copy number: 8.9 (3- 76) underwent treatment with E+B. Six different tumor types were included, with colorectal cancer being the most prevalent (14 patients), followed by glioblastoma (5) and esophageal cancer (2). The cohort included heavily pretreated patients, 13 patients having received two lines of treatment and 10 patients with ≥ three lines of treatments. Four partial responses (PR) and eight cases of stable diseases over 16 weeks (SD16+) were observed, resulting in a CBR of 48% and an ORR of 16%. Especially for patients with squamous cell carcinoma, 3 patients showed PR among 5 patients. The median progression-free survival (PFS) was 3.73 months (95% confidence interval [CI] 2.07∼7.63) and median overall survival (OS) was 7.93 (95% CI 6.53 to NE). The most common adverse events were rash and diarrhea, with no new safety signals. Conclusions E+B showed modest anti-tumor activity with meaningful long term responses in patients with heavily pretreated EGFR amplified solid cancer. NGS testing may help identify new applications for existing drugs, provided additional validation to confirm effectiveness and to find the predictive biomarker of benefit.