BEAT-Meso Trial Evaluates Adding Atezolizumab to Bevacizumab Plus Chemotherapy in Advanced Pleural Mesothelioma

Adding atezolizumab to bevacizumab and chemotherapy improved progression-free survival (PFS) in patients with advanced pleural mesothelioma compared with bevacizumab and chemotherapy, according to findings from the BEAT-meso clinical trial.

However, the triplet did not demonstrate a significant increase in median overall survival (OS), which was the study’s primary endpoint.

The phase 3 trial, presented during the 2024 American Society of Clinical Oncology Annual Meeting, examined the efficacy and safety of the 3-drug regimen versus the bevacizumab/chemotherapy combination as a first-line treatment in patients with malignant mesothelioma from April 2019-March 2022.

All patients (n=400) were given 4-6 cycles of standard chemotherapy consisting of carboplatin AUC 5 plus pemetrexed for 12-18 weeks. Then, the researchers randomized them to 1 of 2 arms. One arm (n=200) received bevacizumab 15 mg/kg intravenously plus chemotherapy. The second arm (n=200) received atezolizumab 1200 mg fixed dose intravenously plus bevacizumab 15 mg/kg and chemotherapy.

Most patients were men (79%), half were former smokers, and they were a median age of 70 years. Nearly 80% had epithelioid histology and 65% had an ECOG performance status of 1.

OS was the primary endpoint with PFS, objective response rate (ORR), disease control rate, duration of response (DoR), and adverse events (AEs) as secondary endpoints.

At a median follow-up of 35 months, the median OS was 20.5 months (95% CI, 17.5-23.3) in the atezolizumab/bevacizumab plus chemotherapy arm and 18.1 months (15.7-20.9) in the bevacizumab/chemotherapy arm.

Furthermore, PFS was significantly longer in the triplet arm with a median of 9.2 months versus 7.6 months with the 2-drug combination (HR=0.72; [0.59 – 0.89], 2-sided stratified P=.0021).

“Histology shows a significant treatment interaction for both PFS and OS,” the researchers said. The OS hazard ratio is 0.51 for non-epithelioid and 1.01 for epithelioid cases (interaction P=.012).

Atezolizumab/bevacizumab plus chemotherapy showed an ORR of 55% versus 49% with bevacizumab plus chemotherapy. The median DoR was 8.2 months and 5.6 months, respectively.

Between the 2 arms, there was no significant difference in global quality of life change.

Patients in both arms experienced AEs. Grade ≥3 treatment-related AEs occurred in 55% of the patients in the triplet arm compared with 47% in the 2-drug arm. Grade 5 AEs also occurred (7 vs 1 patient, respectively).

“The significant increase in median PFS with the addition of atezolizumab did not translate into a significant increase in median OS. Atezolizumab/bevacizumab/chemotherapy demonstrated superiority over (bevacizumab plus chemotherapy) in non-epithelioid cases,” the researchers said.

Reference

Popat S, Felip E, Dafni U, et al. BEAT-meso: A randomized phase III study of bevacizumab (B) and standard chemotherapy (C) with or without atezolizumab (A), as first-line treatment (TX) for advanced pleural mesothelioma (PM)—Results from the ETOP 13-18 trial. Abstract #LBA8002. Presented at the 2024 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2024, Chicago, Illinois.