Immune-related adverse events are associated with efficacy of atezolizumab in patients with advanced NSCLC

An exploratory, post-hoc, pooled analysis of three phase 3 trials with atezolizumab in patients with stage IV non-small cell lung cancer (NSCLC) – IMpower130, IMpower132, and IMpower150 – showed longer overall survival for patients who experience immune-related adverse events.

Immune-related adverse events have been reported in up to 80% of patients receiving immune checkpoint inhibitor monotherapy and up to 95% of patients receiving immune checkpoint inhibitor combination therapy [1]. Increasing evidence suggests that the occurrence of immune-related adverse events may be predictive of improved outcomes in cancers such as NSCLC [2]. The phase 3 IMpower130 (NCT02367781), IMpower132 (NCT02657434), and IMpower150 (NCT02366143) trials evaluated efficacy and tolerability of atezolizumab in NSCLC [3-5]. These 3 trials enrolled a total of 2,503 patients with stage IV NSCLC: 1,577 patients were treated with atezolizumab, 926 patients were in the control arms.

A post-hoc pooled analysis, presented by Dr Mark Socinski (AdventHealth Cancer Institute, FL, USA), explored the association between immune-related adverse events and efficacy in these trials [6]. In the atezolizumab arm, 753 patients experienced an immune-related adverse event, and 824 patients were without immune-related adverse events. In the control arm, 289 patients experienced an immune-related adverse event, whereas 637 patients did not. Patients who experienced an immune-related adverse event had a longer overall survival than those without immune-related adverse events in both the atezolizumab and control arm (see Figure). The median overall survival in the atezolizumab arm was 25.7 months versus 13.0 months for patients with versus without immune-related adverse events (HR 0.69; 95% CI 0.60–0.78). In the control arm, median survival was 20.2 months versus 12.8 months, respectively (HR 0.82; 95% CI 0.68–0.99). In the atezolizumab arm, objective response rate was 61.1% in patients who experienced an immune-related adverse event and 37.2% in patients without immune-related adverse events.

Figure: Overall survival stratified by the occurrence of immune-related adverse events [6]

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   1. Jamal S, et al. Rheumatol. 2020;47:1656-175.
   2. Zhou X, et al. BMC Med. 2020;18:87.
   3. West H, et al. Lancet Oncol. 2019;20:924-937.
   4. Nishio M, et al. Thorac Oncol. 2021;16:653-664.
   5. Socinski MA, et al. N Engl J Med. 2018;378:2288-2301.
   6. Socinski MA, et al. Pooled analyses of immune-related adverse events (irAEs) and efficacy from the phase 3 trials IMpower130, IMpower132, and IMpower150. Abstract 9002, ASCO 2021 Virtual Meeting, 4–8 June.

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Posted on 12 August 202115 February 2024