Association of Immune-Related Adverse Events With Overall Survival in Patients Receiving Atezolizumab-Containing Therapy for Metastatic Nonsquamous NSCLC

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In a pooled analysis reported in JAMA Oncology, Mark A. Socinski, MD, and colleagues found that patients with nonsquamous non–small cell lung cancer (NSCLC) receiving atezolizumab who had grade 1 or 2 immune-related adverse events in clinical trials had improved overall survival vs those with no immune-related adverse events.

Mark A. Socinski, MD

Mark A. Socinski, MD

Study Details

The study used pooled data from the phase III IMpower130, IMpower132, and IMpower150 trials in chemotherapy-naive patients with stage IV disease.

Patients were randomly assigned:

  • 2:1 to atezolizumab with carboplatin plus nab-paclitaxel vs chemotherapy alone in IMpower130
  • 1:1 to atezolizumab with carboplatin or cisplatin plus pemetrexed vs chemotherapy alone in IMpower132
  • 1:1:1 to atezolizumab plus bevacizumab plus carboplatin and paclitaxel, atezolizumab plus carboplatin and paclitaxel, or bevacizumab plus carboplatin and paclitaxel in IMpower150.

Landmark analyses of immune-related adverse event occurrence at 1, 3, 6, and 12 months from baseline were performed in the pooled atezolizumab-containing arms.

Key Findings

Among the 2,503 randomly assigned patients, 1,577 were in the atezolizumab-containing arm and 926 were in the control arm. Immune-related adverse events occurred in 753 patients in the atezolizumab-containing arm and 289 patients in the control arm; no immune-related adverse events were reported in 824 and 637 patients, respectively.

In the atezolizumab-containing arm, median overall survival was 25.7 months (95% confidence interval [CI] = 23.9–29.1 months) among patients with immune-related adverse events vs 13.0 months (95% CI = 11.7–13.9 months) among those without immune-related adverse events (hazard ratio [HR] = 0.69, 95% CI = 0.60–0.78). In the control arm, median overall survival was 20.2 months (95% CI = 18.2–22.8 months) among patients with immune-related adverse events vs 12.8 months (95% CI = 12.0–13.9 months) among those without such events (HR = 0.82, 95% CI = 0.68–0.99).

In the atezolizumab-containing arm, hazard ratios for overall survival for patients with grade 1 or 2 vs no immune-related adverse events in the 1-, 3-, 6-, and 12-month subgroups were 0.78 (95% CI = 0.65–0.94), 0.74 (95% CI = 0.63–0.87), 0.77 (95% CI = 0.65–0.90), and 0.72 (95% CI = 0.59–0.89), respectively. Hazard ratios for patients with grade ≥ 3 vs no immune-related adverse events were 1.25 (95% CI = 0.90–1.72), 1.23 (95% CI = 0.93–1.64), 1.1 (95% CI = 0.81–1.42), and 0.87 (95% CI =0.61–1.25), respectively.

The investigators concluded, “In this pooled analysis of three randomized clinical trials, longer overall survival was observed in patients with vs without mild to moderate immune-related adverse events in both arms and across landmarks. These findings further support the use of first-line atezolizumab-containing regimens for advanced nonsquamous NSCLC.”

Dr. Socinski, of AdventHealth Cancer Institute, Orlando, Florida, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was supported by F. Hoffmann-La Roche Ltd. For full disclosures of the study authors, visit

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