An exploratory pooled analysis of immune-related adverse events (irAEs) and efficacy from multiple phase 3 trials involving patients with non-small cell lung cancer (NSCLC) revealed that those who experienced irAEs had longer overall survival (OS) compared with patients who did not in both the atezolizumab-containing and control arms.

This research was presented by Mark Socinski, MD, PhD, of the AdventHealth Cancer Institute in Orlando, Florida, at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

A majority of the patients receiving immune checkpoint inhibitors develop irAEs. Increasing evidence suggests that the occurrence of irAEs with anti-programmed cell death 1 (anti-PD-1) and programmed cell death ligand 1 (PD-L1) immune checkpoint inhibitors may be predictive of improved outcomes in NSCLC.

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Atezolizumab is an engineered anti-PD-L1 antibody that has shown efficacy and tolerability in NSCLC and is currently approved in the first-line, second-line, and later settings. 

The research team conducted post hoc exploratory analyses evaluating the association between irAEs and efficacy using pooled data from phase 3 IMpower130 ( Identifier: NCT02367781), IMpower132 ( Identifier: NCT02657434), and IMpower150 ( Identifier: NCT02366143) trials that tested atezolizumab in combination with chemotherapy with or without bevacizumab as first-line treatment of NSCLC.

Treatment-naive patients with nonsquamous stage IV NSCLC were randomly assigned to arm A (atezolizumab + carboplatin + nab-paclitaxel) or arm B (carboplatin + nab-paclitaxel) in IMpower130; arm A (carboplatin or cisplatin alone) or arm B (carboplatin or cisplatin + atezolizumab) in IMpower132; and arm A (atezolizumab + carboplatin + paclitaxel), arm B (atezolizumab + carboplatin + paclitaxel + bevacizumab), or arm C (carboplatin + paclitaxel + bevacizumab) in IMpower150 trial.

The study included a total of 2503 patients (1577 in the atezolizumab-containing arm and 926 in the control arm). At baseline, the number of patients with irAEs in the atezolizumab vs control arms was 753 vs 289. The number of patients without irAEs in the atezolizumab vs control arms was 824 vs 637.

Patients who experienced irAEs showed longer overall survival (OS) than those who did not in both the atezolizumab-containing (hazard ratio [HR], 0.69; 95% CI, 0.60-0.78) and control arms (HR, 0.82; 95% CI, 0.68-0.99).

Forty-eight percent of the patients in the atezolizumab-containing arm and 32% in the control arm developed any-grade irAEs. 11% and 5% of the patients in the atezolizumab-containing and control arms developed grade 3 to 5 irAEs, respectively. Rash (28% vs 18%), hepatitis (15% vs 10%), and hypothyroidism (12% vs 4%) were the most frequent irAEs in atezolizumab-containing vs control arms. The median time to onset of the first irAE in the atezolizumab-containing and control arms was 1.7 and 1.4 months, respectively.

Patients with grade 1/2 irAEs had the longest OS in the atezolizumab-containing arm, and patients with grade 3 to 5 irAEs had the shortest OS, possibly due to treatment interruption or discontinuation.

In both the arms, landmark analyses at 1, 3, 6, and 12 months showed longer OS in patients who experienced irAEs compared to those who did not. Compared to the control arm, patients benefited from atezolizumab regardless of whether they had experienced irAEs.

“Data from these analyses suggest an association between irAEs and efficacy in patients with NSCLC and further support the use of atezolizumab combined with chemotherapy, with or without bevacizumab, in the first-line treatment setting,” Dr Socinski said.

Disclosure: This research study was funded by F. Hoffmann-La Roche, Ltd. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


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. J Clin Oncol. 2021;39:(suppl 15; abstr 9002). doi:10.1200/JCO.2021.39.15_suppl.9002

This article originally appeared on Cancer Therapy Advisor