BEAT-meso, ETOP 13-18

Background

Phase III, open-label RCT (BEAT-meso / ETOP 13-18). N=400 treatment-naive patients with advanced diffuse pleural mesothelioma, stratified by histology and stage. Epithelioid histology 78%, ECOG PS 1 in 65%.

Interventions and follow up

Arm A: Atezolizumab 1200 mg IV + bevacizumab 15 mg/kg IV + carboplatin AUC + pemetrexed 500 mg/m² IV Q3W, then atezolizumab + bevacizumab maintenance
Arm B: Bevacizumab 15 mg/kg IV + carboplatin AUC + pemetrexed 500 mg/m² IV Q3W, then bevacizumab maintenance
Primary endpoint: OS
mFollow up: 35 mo

Results

OS (overall): 20.5 vs 18.1mo, HR 0.84, 95% CI 0.66–1.06, P=.14 (not significant)
PFS: 9.2 vs 7.6mo, HR 0.72, 95% CI 0.59–0.89, P=.002
OS non-epithelioid: HR 0.51, 95% CI 0.32–0.80
OS epithelioid: HR 1.01, 95% CI 0.77–1.32

Adverse events

Overall: grade ≥3 treatment-related AEs 55% vs 47%.
Immune-related: higher with atezolizumab, consistent with known PD-L1 inhibitor profile.

Conclusions

Adding atezolizumab improved PFS but did NOT significantly improve OS in the overall population. A significant OS and PFS benefit was seen in non-epithelioid mesothelioma, suggesting histology-specific efficacy.

Key Limitations

Negative for the primary OS endpoint in the overall population. Subgroup OS benefit in non-epithelioid disease is hypothesis-generating, not powered. Open-label design. PFS gain modest (~1.6mo). No PD-L1 biomarker selection. Adds atezolizumab to a chemo-bevacizumab backbone not universally used.

Clinical Context

BEAT-meso did not establish a new standard given the negative overall OS. First-line IO for pleural mesothelioma remains anchored by CheckMate 743 (nivolumab + ipilimumab, OS benefit, especially non-epithelioid) and chemo + pembrolizumab (KEYNOTE-483/IND227). Histology-driven IO benefit (non-epithelioid) is a recurring signal across trials.

References