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Pooled Analyses of Immune-Related Adverse Events and Efficacy from IMpower130, IMpower132, and IMpower150

Conference Correspondent  - AACR & ASCO 2021 - Midyear Review

Overall survival is longer for patients with advanced non–small-cell lung cancer who received atezolizumab and had immune-related adverse events versus patients who received atezolizumab and did not have immune-related adverse events.

Inhibitors of PD-L1 and PD-1 have transformed the treatment of advanced non–small-cell lung cancer (NSCLC). Evidence suggests that the occurrence of immune-related adverse events (irAEs) with these agents may predict improved outcomes in cancers, including NSCLC. Atezolizumab, an anti–PD-L1 agent, has shown efficacy and tolerability in NSCLC and is currently approved in first- and later-line settings. The phase 3 IMpower130, IMpower132, and IMpower150 trials evaluated atezolizumab + chemotherapy ± bevacizumab as first-line therapy for patients with NSCLC. At the American Society of Clinical Oncology 2021 annual meeting, researchers evaluated the nature and magnitude of the association between irAEs and efficacy in these trials.1

Each of the 3 trials enrolled treatment-naïve patients with nonsquamous stage IV NSCLC. Patients were randomized to carboplatin + nab-paclitaxel alone or with atezolizumab in IMpower130; carboplatin or cisplatin alone or with atezolizumab in IMpower132; atezolizumab + bevacizumab + carboplatin + paclitaxel, atezolizumab + bevacizumab + paclitaxel, or bevacizumab + carboplatin + paclitaxel in IMpower150. Data were pooled (data cutoffs: March 15, 2018 [IMpower130]; May 22, 2018 [IMpower132]; September 13, 2019 [IMpower150]) and analyzed by treatment (atezolizumab- containing vs control) and irAE status. A time-dependent Cox model and landmark analyses at 1, 3, 6, and 12 months were used to control for immortal bias. Study protocols required atezolizumab treatment interruption or discontinuation for grade ≥3 irAEs.1

A total of 2503 patients were included in the analysis: 1577 who received atezolizumab and 926 in the control group.1 In both arms, baseline characteristics were generally balanced between patients with irAEs (atezolizumab, n = 753; control, n = 289) and without irAEs (atezolizumab, n = 824; control, n = 637).1 Any-grade irAEs occurred in 48% of atezolizumab patients and 32% of patients in the control group; grade 3 to 5 irAEs occurred in 11% of atezolizumab patients and in 5% of patients in the control group.1

The most common irAEs with atezolizumab compared with control were rash (28% vs 18%), hepatitis (lab abnormalities; 15% vs 10%) and hypothyroidism (12% vs 4%).1 Median time to onset of first irAE was 1.7 (atezolizumab) versus 1.4 months (control).1 Hazard ratios (HRs) for overall survival (OS) from the time-dependent Cox model between patients with or without irAEs were 0.69 (95% confidence interval [CI], 0.60-0.78) in the atezolizumab arm and 0.82 (95% CI, 0.68-0.99) in the control arm.1 Excluding rash (perceived as the least specific irAE), OS HRs were 0.75 (95% CI, 0.65-0.87) and 0.90 (95% CI, 0.71-1.12), respectively.1

In this exploratory pooled analysis, patients with irAEs had longer OS compared with patients who did not experience irAEs in atezolizumab-containing and control arms per the time-dependent Cox model and landmark analyses (for patients receiving atezolizumab who experienced irAE, median OS was 25.7 months; for patients receiving atezolizumab who did not experience irAE, median OS was 13.0 months).1 This trend remained for patients in the atezolizumab arm after excluding rash from the list of irAEs.1 Landmark analyses show that, in the atezolizumab arm, patients with grade 1/2 irAEs had longer OS compared with patients with grade ≥3 irAEs, potentially due to treatment interruption and/or discontinuation.1

These data suggest an association between irAEs and efficacy in patients with NSCLC and further support treatment with atezolizumab combined with chemotherapy, with or without bevacizumab, in the first-line setting.1

Reference

1. Socinski MA, Jotte RM, Cappuzzo F, et al. Pooled analyses of immune-related adverse events (irAEs) and efficacy from the phase 3 trials IMpower130, IMpower132, and IMpower150. Presented at: 2021 American Society of Clinical Oncology (ASCO) Annual Meeting; June 4-8, 2021. Abstract 9002.

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