Atezolizumab Plus Chemotherapy for First-Line Treatment of Nonsquamous NSCLC: Results From the Randomized Phase 3 IMpower132 Trial

Nishio, Makoto; Barlési, Fabrice; West, Howard; Ball, S.; Bordoni, Rodolfo; Cobo, Manuel; Longeras, Pascale Dubray; Goldschmidt, Jerome H.; Novello, Silvia; Orlandi, F; Sanborn, Rachel E.; Szalai, Zsuzsanna; Ursol, Grigoriy; Mendus, Diana; Wang, Lijia; Wen, Xiaohui; McCleland, Mark L.; Hoang, Tien; Phan, See; Socinski, Mark A.

doi:10.1016/j.jtho.2020.11.025

Cited by 306 publications

(302 citation statements)

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“…1 . Finally, 28 eligible articles reporting 24 RCTs (23 phase 3 and 1 phase 2 trials) with 13918 patients (11698 of smokers and 2220 of never smokers) were eligible for inclusion [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] . Because one studies [10] provided pooled OS data of CheckMate-017 [9] , and -057 [11] , the pooled data were used instead of data from the individual trials in this meta-analysis.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, never smokers should obtain less benefit from ICIs compared to smokers theoretically. However, this hypothesis has not been confirmed by current ICIs trials, in which inconsistent results were observed [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] . Some previous meta-analyses [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] have attempted to clarify the relationship between smoking and the efficacy of ICIs in NSCLC, while the lack of statistical power due to limitations such as small number of studies, small sample size, and few subgroup analysis prevents a final conclusion.…”

Section: Introductionmentioning

confidence: 99%

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The effect of smoking status on efficacy of immune checkpoint inhibitors in metastatic non-small cell lung cancer: A systematic review and meta-analysis

et al. 2021

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Background: It remains uncertain whether smoking status can effect efficacy of immune checkpoint inhibitors (ICIs) in metastatic non-small cell lung cancer (NSCLC). We performed a meta-analysis to address this issue.Patients and methods: PubMed, Embase, Cochrane Library, Web of Science, and international meetings were searched until April 1, 2021, for phase 2 and 3 randomized controlled trials (RCTs) which compared ICIs with chemotherapy (CT) and reported overall survival (OS) and/or progression-free survival (PFS) data according to smoking status. This meta-analysis was registered in INPLASY platform (#INPLASY202140025). The random-effect model was used for statistical analysis. Findings: Twenty-eight articles from 24 RCTs including 13918 patients were eligible. ICIs significantly prolonged OS than CT in smokers (hazard ratio [HR] = 0.75, 95% confidence interval [CI]: 0.69-0.81), but not in never-smokers (HR = 0.87, 95% CI: 0.74-1.04); while there was no significant treatment-smoking interaction (P interaction = 0.11). Significant heterogeneity was observed for both smokers (OS: I 2 = 60%, P = 0.0002; PFS: I 2 = 74%, P < 0.0001) and never smokers (PFS: I 2 = 69%, P < 0.0001). Subgroup analyses revealed that ICIs monotherapy significantly improved OS in smokers (HR = 0.76, 95% CI: 0.69-0.85) but not in never-smokers (HR = 0.93, 95% CI: 0.77-1.12, P interaction = 0.07), and treatment-smoking interaction was significant in patients with PD-L1 50% (HR, 0.61 vs 1.18; P interaction = 0.005). ICIs plus CT achieved better OS either in smokers or never-smokers (HR, 0.76 vs 0.61; P interaction = 0.39), while dual ICIs combination prolonged OS only in smokers but never-smokers (HR, 0.68 vs 1.02; P interaction = 0.02). Interpretation: Either ICIs monotherapy or combination therapy was superior to CT in smokers. While ICIs monotherapy and dual ICIs combination were less effective in never-smokers, and ICIs plus CT might be the optimal selection. Nevertheless, given the limitation of the high heterogeneity of studies included, the findings need to be confirmed by future RCTs focusing on this subject.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The effect of smoking status on efficacy of immune checkpoint inhibitors in metastatic non-small cell lung cancer: A systematic review and meta-analysis

et al. 2021

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“…First, despite all included studies being RCTs and most of them being phase III trials, all data of patients with and without BMs were extracted from subgroup analyses of these RCTs, which might result in a potential imbalance in baseline characteristics between the two sets of patients. Second, some RCTs, such as IMpower series studies (46)(47)(48)(49)(50) and CheckMate 017 (51) and 026 (52), were excluded from our study because of the non-reporting of survival information of patients with BMs. This might result in a selection bias to some extent.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Asymptomatic and/or Treated Brain Metastases on Efficacy of Immune Checkpoint Inhibitors in Metastatic Non–Small Cell Lung Cancer: A Meta-Analysis

Zhang

Liu

et al. 2021

Front. Oncol.

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BackgroundTo assess the effect of asymptomatic and/or treated brain metastases (BMs) on the efficacy of immune checkpoint inhibitors (ICIs) in metastatic non-small cell lung cancer (NSCLC).Patients and MethodsPubMed, Embase, Cochrane Library, Web of Science, and recent meetings were searched for randomized controlled trials (RCTs). The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS).ResultsSeventeen articles reporting 15 RCTs with 10,358 patients (1,199 with and 9,159 without BMs) were eligible. ICIs were associated with longer OS and PFS than those in chemotherapy either in patients with (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.51–0.82 and HR, 0.60; 95% CI, 0.45–0.79) or without BMs (HR, 0.74; 95% CI, 0.70–0.78 and HR, 0.70; 95% CI, 0.57–0.86); no significant difference in the pooled HRs for OS (Pinteraction = 0.29) and PFS (Pinteraction = 0.37) was observed between the two patient populations. Subgroup analyses revealed that either ICI monotherapy or combination therapy significantly improved OS and PFS compared with those in chemotherapy both for patients with and without BMs. Superior OS benefit from ICI combination therapy than that in monotherapy was observed in patients with BMs (HR, 0.49 vs. 0.81, Pinteraction = 0.005) but not in patients without BMs (HR, 0.71 vs. 0.76, Pinteraction = 0.27).ConclusionThere was no compelling statistical evidence that the efficacy of ICIs in metastatic NSCLC was modified by the presence of asymptomatic and/or treated BMs. Patients with BMs were likely to obtain more OS benefit from ICI combination therapy than that from monotherapy.

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“…Additionally, in the IMpower130 trial ( 18 ), a randomized, phase III study (investigating atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy vs. chemotherapy alone as a first-line chemotherapy for metastatic non-squamous non-small-cell lung cancer), 3 of 473 patients (0.63%) developed encephalitis or meningitis. Furthermore, in the Impower 132 trial ( 19 ), a randomized, phase III study (investigating atezolizumab plus carboplatin or cisplatin and pemetrexed vs. carboplatin or cisplatin and pemetrexed), 4 of 291 patients (1.37%) developed encephalitis or meningitis. In the Impower 150 study ( 20 ), a randomized, phase III study (atezolizumab in combination with carboplatin plus paclitaxel with or without bevacizumab vs. carboplatin plus paclitaxel and bevacizumab), 1 of 393 patients (0.25%) developed meningoencephalitis.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Durvalumab-Associated Encephalitis in Extensive-Stage Small Cell Lung Carcinoma

et al. 2021

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In recent years, the clinical importance of immunotherapy has been demonstrated in the treatment of extensive-stage small-cell lung cancer (ES-SCLC). However, immune checkpoint inhibitors (ICIs) have been shown to cause immune-related adverse events (irAEs), including autoimmune encephalitis. Here, we describe th treatment of a patient with ES-SCLC who developed immune-related encephalitis. A 68-year-old Japanese woman with ES-SCLC treated with carboplatin plus etoposide plus durvalumab 20 days earlier was admitted to our hospital with a high fever and anorexia. Her symptoms gradually worsened over time, and she had a headache daily and showed reduced levels of consciousness. An electroencephalogram showed diffuse slow waves, and there was a slight increase in cell counts and an increase in protein levels in the cerebrospinal fluid. The patient was diagnosed with durvalumab-associated encephalitis. Her symptoms improved immediately after steroid pulse therapy. Following steroid pulse therapy, oral prednisolone (1 mg/kg) was administered, and then, the dose was gradually reduced. Subsequently, treatment with carboplatin plus etoposide without durvalumab was restarted. In conclusion, this study shows the efficacy of steroid therapy in the treatment of durvalumab-induced encephalitis in ES-SCLC.

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Atezolizumab Plus Chemotherapy for First-Line Treatment of Nonsquamous NSCLC: Results From the Randomized Phase 3 IMpower132 Trial

Cited by 306 publications

References 23 publications

The effect of smoking status on efficacy of immune checkpoint inhibitors in metastatic non-small cell lung cancer: A systematic review and meta-analysis

The effect of smoking status on efficacy of immune checkpoint inhibitors in metastatic non-small cell lung cancer: A systematic review and meta-analysis

The Effect of Asymptomatic and/or Treated Brain Metastases on Efficacy of Immune Checkpoint Inhibitors in Metastatic Non–Small Cell Lung Cancer: A Meta-Analysis

Case Report: Durvalumab-Associated Encephalitis in Extensive-Stage Small Cell Lung Carcinoma

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