Combination Therapy of Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel for Metastatic Non-squamous Non-small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitor Resistance and EGFR Mutations

Introduction: Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) combination therapy has a potential efficacy in a specific subset of non-squamous non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor ( EGFR ) mutations following tyrosine kinase inhibitor (TKI) treatment. However, there is a dearth of investigations on the effectiveness of ABCP therapy as the primary outcome of EGFR-TKI use. Methods: A single-center retrospective analysis was performed on 24 cases of stage IV EGFR-positive nonsquamous NSCLC patients who received one or more lines of EGFR-TKI therapy and subsequently initiated ABCP therapy within the timeframe of April 1, 2019, to April 30, 2023. This study assessed overall survival and progression-free survival associated with ABCP therapy, further analyzing the overall survival data based on EGFR subgroups. Results: The mean age of the cohort was 65 +/- 9 years with 14 females (58%). The performance status (PS) was recorded as 0 in 13 out of 24 patients (54%) and 1 in 11 out of 24 patients (46%). Thirteen (54%) patients had a history of smoking. Adenocarcinoma histology was prevalent in all cases. The EGFR mutations included Ex19del in 14 patients (58%) and L858R in 10 (42%) patients. At ABCP therapy initiation, liver metastases were evident in three cases (13%) and brain metastases in eight (33%). Programmed death ligand 1 (22C3) expression levels varied, with <1%, 1-49%, and >= 50% observed in five, 11, and five cases, respectively, while data were missing for three cases. The median follow-up duration was 14.1 months, with median overall survival estimated at 23.6 months (95% CI: 14.5 months- not reached) and median progression-free survival at 5.6 months (95% CI: 4.9-11.5 months). The EGFR L858R mutation showed a favorable trend in overall survival compared with the EGFR Ex19del mutation (not evaluated vs. 23.6 months). Conclusions: ABCP therapy forEGFR-positive EGFR-positive non-squamous NSCLC is a promising option, similar to immune checkpoint inhibitor-free platinum-based combination therapy. Therefore, prospective trials are necessary to confirm the efficacy of these treatments.