IMpower150 Study: Atezolizumab in Combination with Bevacizumab and Chemotherapy in EGFR-Mutated NSCLC

Researchers reported improved overall survival in patients with nonsquamous non–small-cell lung cancer with EGFR mutations.

Atezolizumab is a programmed cell death-ligand 1 inhibitor that may have enhanced efficacy in combination with bevacizumab, which inhibits vascular endothelial growth factor immunosuppression and promotes T-cell tumor infiltration. IMpower150 was a randomized phase 3 study that evaluated first-line treatment with atezolizumab and/or bevacizumab with carboplatin + paclitaxel in patients with nonsquamous non–small-cell lung cancer (NSCLC), including those with EGFR mutations. Previously reported results demonstrated that the addition of atezolizumab to bevacizumab in combination with carboplatin + paclitaxel significantly prolonged progression-free survival (PFS) and overall survival (OS). The researchers reported the results of the final efficacy analysis during the ESMO Virtual Congress 2020.

A total of 1202 patients were randomized to atezolizumab + bevacizumab + carboplatin/paclitaxel (ABCP); atezolizumab + carboplatin/paclitaxel (ACP); or bevacizumab + carboplatin/paclitaxel (BCP) for 4 or 6 cycles per investigator decision, followed by maintenance every 3 weeks with atezolizumab + bevacizumab, atezolizumab, or bevacizumab, respectively. A total of 123 patients had EGFR mutations, including 91 with a sensitizing mutation. The co-primary end points were OS and investigator-assessed PFS in the intention-to-treat (ITT)–wild-type population (which excluded patients with EGFR or ALK alterations). Exploratory analyses were performed for OS in patients with EGFR mutations, those with sensitizing EGFR mutations (exon 19 deletions or L858R mutations), and those with sensitizing EGFR mutations who received prior tyrosine kinase inhibitors (TKIs).

In the ITT population, median follow-up was 39.3 months (data cutoff, September 13, 2019). Among patients with EGFR mutations, the median OS was 26.1 months with ABCP, 21.4 months with ACP, and 20.3 months with BCP (hazard ratios [HRs] for ABCP vs BCP and ACP vs BCP were 0.91 [95% confidence interval (CI), 0.53-1.59] and 1.16 [95% CI, 0.71-1.89], respectively). Among patients with sensitizing EGFR mutations, the median OS was 29.4 months with ABCP, 19.0 months with ACP, and 18.1 months with BCP (HRs for ABCP vs BCP and ACP vs BCP were 0.60 [95% CI, 0.31-1.14] and 1.0 [95% CI, 0.57-1.74], respectively). Among patients who received prior TKI therapy, median OS was 27.8 months with ABCP, 14.9 months with ACP, and 18.1 months with BCP (HRs for ABCP vs BCP and ACP vs BCP were 0.74 [95% CI, 0.38-1.46] and 1.22 [95% CI, 0.68-2.22], respectively).

The researchers concluded that the addition of atezolizumab to bevacizumab in combination with carboplatin + paclitaxel continued to show improvement in OS and may provide a new option in patients with NSCLC and sensitizing EGFR mutations, including those who had prior treatment failure with TKIs.

Reference
Reck M, et al. ESMO 2020. 1293P.