KEY TAKEAWAYS
- This phase II study assessed the impact of bevacizumab in the atezolizumab, carboplatin, and etoposide regimen to treat ES-SCLC pts.
- The primary endpoint was 1-year OS. Secondary endpoints were PFS, OS, and AEs.
- The study showed that bevacizumab, when added to carboplatin-etoposide-atezolizumab, is generally well-tolerated in ES-SCLC patients.
Prior research has shown that integrating PD-L1 inhibition with platinum-etoposide boosts survival rates for patients with extensive-stage small-cell lung cancer (ES-SCLC). Additionally, Vascular Endothelial Growth Factor (VEGF) plays a role in the immunosuppressive aspects of the SCLC tumor microenvironment.
The previous phase III FARM6PMFJM trial indicated that adding bevacizumab, an anti-VEGF antibody, to platinum-etoposide chemotherapy is safe and potentially effective. Given the synergistic anti-tumor effects observed when combining PD-L1 and VEGF inhibition in SCLC models, researchers theorized that bevacizumab would further enhance the efficacy of a regimen including atezolizumab, carboplatin, and etoposide in treating ES-SCLC patients (pts).
This investigator-led multicenter phase II single-arm study, sponsored by GOIRC and supported by Roche, evaluated the combination of bevacizumab, atezolizumab, carboplatin, and etoposide as a first-line treatment for ES-SCLC. Patients were administered carboplatin (AUC 5 d1), etoposide (100mg/sqm d1-3), bevacizumab (7.5mg/kg d1), and atezolizumab (1200mg d1) every three weeks for 4-6 courses during the induction phase.
This was followed by a maintenance phase of bevacizumab and atezolizumab every three weeks, up to 18 cycles. Patients with asymptomatic or treated brain metastases were eligible. Treatment beyond RECIST-defined progression was allowed if pts showed clinical benefit. The primary endpoint was one-year overall survival (OS), while secondary endpoints included progression-free survival (PFS), OS, and adverse events (AEs).
Enrollment for the trial was completed in March 2022, and as of the last data cut-off on August 31st, 2022, the primary endpoint data was still not mature. Of the 53 pts enrolled, with a median age of 65 (ranging from 46 to 79), 98% were current or former smokers, and 42% had an ECOG PS of 1. The most common sites for metastasis were liver (26%), bones (21%), and brain (19%), with a median target lesion diameter sum of 119.5 mm. Of the 51 pts with available treatment data, 78% completed the induction phase, and 73% proceeded to maintenance, receiving a median of four maintenance courses.
The median total number of treatment courses was 7. In 17 cases (33%), atezolizumab was continued beyond disease progression, with a median of 2 additional courses. Eleven pts remained on treatment as of the data cut-off. Table 1 details the most frequent adverse events, and 16 instances of potential treatment-related serious adverse events (SAEs) were reported, such as neutropenia and pulmonary embolism.
Adding bevacizumab to a regimen of carboplatin, etoposide, and atezolizumab in ES-SCLC pts is generally well-tolerated. Survival analysis results will be presented at the upcoming conference.
Source: https://cattendee.abstractsonline.com/meeting/10925/presentation/1022
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04730999
Lamberti, G., Rihawi, K., Riccardi, F., Mazzoni, F., Follador, A., Bonetti, A., Giardina, D., Genova, C., Bertolini, F., Frassoldati, A., Brighenti, M., Colantonio, I., Pasello, G., Ficorella, C., Cinieri, S., Tiseo, M., Fancelli, S., Andrini, E., Targato, G., Tognetto, M., Boni, L., Ardizzoni, A. Carboplatin, Etoposide, Bevacizumab, and Atezolizumab in Patients with Extensive-Stage SCLC – GOIRC-01-2019 CeLEBrATE Trial.
