Background
Phase III ATTLAS trial; N≈220 advanced NSCLC with EGFR or ALK alterations after TKI failure; open-label. Evaluated adding atezolizumab + bevacizumab to chemotherapy.
Interventions and follow up
Arm A: Atezolizumab 1200 mg IV Q3W + bevacizumab 15 mg/kg IV Q3W + carboplatin/paclitaxel Q3W (ABCP)
Arm B: Platinum-doublet chemotherapy alone (carboplatin + pemetrexed or paclitaxel, per genotype)
Primary endpoint: PFS
mFollow up: ~18mo
Arm B: Platinum-doublet chemotherapy alone (carboplatin + pemetrexed or paclitaxel, per genotype)
Primary endpoint: PFS
mFollow up: ~18mo
Results
mPFS: 8.5 vs 5.6mo, HR 0.62, 95% CI ~0.45–0.85, P=.004
mPFS by PD-L1: HR 0.47 (≥1%), 0.41 (≥10%), 0.24 (≥50%) — greater benefit at higher PD-L1
mOS: 20.6 vs 20.3mo (NS)
ORR: 69.5% vs 41.9%, P<.001
mPFS by PD-L1: HR 0.47 (≥1%), 0.41 (≥10%), 0.24 (≥50%) — greater benefit at higher PD-L1
mOS: 20.6 vs 20.3mo (NS)
ORR: 69.5% vs 41.9%, P<.001
Adverse events
Overall: Grade ≥3 AEs 69% (ABCP) vs 55% (chemo).
Hematologic: neutropenia 18% vs 12%.
Hematologic: neutropenia 18% vs 12%.
Conclusions
In EGFR/ALK+ NSCLC post-TKI, adding atezolizumab + bevacizumab to chemo significantly improved PFS and response, especially at higher PD-L1. OS was similar, suggesting delayed progression without clear survival extension (possibly due to subsequent therapies).
Key Limitations
Open-label; modest N; no OS benefit; mixed EGFR/ALK population; higher toxicity with quadruplet.
Clinical Context
Supports the ABCP (anti-VEGF + anti-PD-L1 + chemo) backbone (cf. IMpower150) for TKI-resistant EGFR/ALK NSCLC; contrasts with negative KEYNOTE-789 (no anti-VEGF). Not a regulatory registration trial; ESMO views the role of IO + anti-angiogenic in this setting as still evolving.
References