Immune-Related Adverse Events Associated With Improved Atezolizumab Outcomes Among Patients With NSCLC

Pooled data from 3 randomized clinical trials demonstrated longer overall survival (OS) in patients with non-small cell lung cancer (NSCLC) who experienced mild to moderate immune-related adverse events (irAEs) related to treatment with immune checkpoint inhibitor chemoimmunotherapy combinations involving atezolizumab.

Mark A Socinski, MD, AdventHealth Cancer Institute, Orlando, FL, and colleagues wrote, “The potential of irAEs to predict atezolizumab efficacy will prove useful for the management of NSCLC and may help improve treatment adherence.”

The pooled analyses evaluated data from the phase 3, multicenter, open-label, randomized IMpower130, IMpower132, and IMpower150 clinical trials, which enrolled chemotherapy-naïve adult patients with stage 4 nonsquamous NSCLC. In IMpower130, patients were randomly assigned to receive either atezolizumab with carboplatin plus nab-paclitaxel, or chemotherapy alone; IMpower132 randomized patients to receive atezolizumab with carboplatin or cisplatin plus pemetrexed, or chemotherapy alone; and IMpower150 randomized patients to receive atezolizumab plus bevacizumab plus carboplatin and paclitaxel, atezolizumab plus carboplatin and paclitaxel, or bevacizumab plus carboplatin and paclitaxel.

Results from data pooled from these 3 studies was analyzed by treatment (atezolizumab-containing vs control), irAE status (with vs without), and highest irAE grade (1 to 2 vs 3 to 5). Hazard ratio (HR) of OS was estimated using irAE occurrence at 1, 3, 6, and 12 months from baseline. Overall, 2503 patients randomized patients were included, with 1577 patients in the atezolizumab treatment cohort and 926 patients in the control cohort.

Across all subgroups, patients in the atezolizumab group who experienced an irAE had the longest median OS, while patients in the control group who did not experienced an irAE had the shortest median OS. In both groups, patients who had irAEs had longer OS than those without an irAE. In the atezolizumab group, OS HRs (95% confidence interval [CI]) in patients with grade 1 to 2 irAEs vs those without irAEs was 0.78 (0.65 to 0.94) at 1 month, 0.74 (0.63 to 0.87) at 3 months, 0.77 (0.65 to 0.9) at 6 months, and 0.72 (0.59-0.89) at 12 months. Comparatively, OS HRs (95% CI) with grade 3 to 5 irAEs vs those without was 1.25 (0.90 to 1.72) at 1 month, 1.23 (0.93-1.64) at 3 months, 1.1 (0.81 to 1.42) at 6 months, and 0.87 (0.61-1.25) at 12 months.

Dr Socinski et al concluded, “This pooled analysis of data from 3 atezolizumab randomized clinical trials suggests as association between mild to moderate irAEs and efficacy in NSCLC.” They added, “These data further support the use of atezolizumab combined with chemotherapy, with or without bevacizumab, for first-line treatment of advanced nonsquamous NSCLC.”

Source:

Socinski MA, Jotte RM, Cappuzzo F, et al. Association of immune-related adverse events with efficacy of atezolizumab in patients with non-small cell lung cancer: pooled analyses of the phase 3 IMpower130, IMpower132, and IMpower150 randomized clinical trials. JAMA Oncol. Published online: February 16, 2023. doi: 10.1001/jamaoncol.2022.7711