Addition of Atezolizumab to Bevacizumab and Chemotherapy in First-Line Treatment of Metastatic Nonsquamous NSCLC
As reported at the 2018 ASCO Annual Meeting and in The New England Journal of Medicine by Socinski et al, the phase III IMpower150 trial has shown that the addition of atezolizumab (Tecentriq) to bevacizumab (Avastin) plus chemotherapy significantly improved progression-free and overall survival in first-line treatment of metastatic nonsquamous non–small cell lung cancer (NSCLC), with benefit being observed irrespective of programmed cell death ligand 1 (PD-L1) expression or EGFR or ALK alteration status.
Study Details
In the open-label trial, a total of 1,202 patients from 240 sites in 26 countries were randomly assigned to receive atezolizumab plus carboplatin plus paclitaxel (ACP, n = 402), bevacizumab plus carboplatin plus paclitaxel (BCP, n = 400), or atezolizumab plus BCP (ABCP, n = 400) every 3 weeks for 4 or 6 cycles, followed by maintenance therapy with atezolizumab, bevacizumab, or both. Randomization was stratified by sex, presence of liver metastases, and PD-L1 tumor expression.
The wild-type genotype population (86.5% of the total population), excluding patients with EGFR or ALK alterations, consisted of 1,040 patients, with 348 in the ACP group, 336 in the BCP group, and 356 in the ABCP group. Among the wild-type population, high expression of an effector T-cell (Teff) gene signature was present in 445 patients, including 161 in the ACP group, 129 in the BCP group, and 155 in the ABCP group.
The primary endpoints were investigator-assessed progression-free survival among patients in the wild-type population and among wild-type patients with high Teff expression (Teff-high) and overall survival in the wild-type population. The statistical plan called for comparison of the ABCP group vs the BCP group before comparison of the ACP vs BCP groups.
Efficacy Outcomes
In the wild-type population, median progression-free survival was 8.3 months in the ABCP group vs 6.8 months in the BCP group (hazard ratio [HR] = 0.62, P < .001). In the Teff-high wild-type population, median progression-free survival was 11.3 vs 6.8 months in the 2 groups (HR = 0.51, P < .001). In the overall wild-type population, median overall survival was 19.2 months in the ABCP group vs 14.7 months in the BCP group (HR = 0.78, P = .02).
Median progression-free survival was longer in the ABCP group vs the BCP group in the total intention-to-treat population (8.3 vs 6.8 months, stratified HR = 0.61, 95% confidence interval [CI] = 0.52–0.72), among patients with low (< 50% of tumor cells and < 10% of infiltrating cells) or negative PD-L1 expression (8.0 vs 6.8 months, unstratified HR = 0.68, 95% CI = 0.56–0.82), among those with high PD-L1 expression (12.6 vs 6.8 months, unstratified HR = 0.39, 95% CI = 0.25–0.60), those with low Teff gene-signature expression (7.3 vs 7.0 months, unstratified HR = 0.76, 95% CI = 0.60–0.96), and those with baseline liver metastases (7.4 vs 4.9 months, unstratified HR = 0.42, 95% CI = 0.26–0.66).
The safety profile of ABCP was reported to be consistent with previously reported profiles of the individual drugs.
The investigators concluded, “The addition of atezolizumab to bevacizumab plus chemotherapy significantly improved progression-free survival and overall survival among patients with metastatic nonsquamous NSCLC, regardless of PD-L1 expression and EGFR or ALK genetic alteration status.”
The study was funded by F. Hoffmann–La Roche/Genentech.
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