Safety of adjuvant atezolizumab after pneumonectomy/bilobectomy in stage II-IIIA non–small cell lung cancer in the randomized phase III IMpower010 trial

Lee, Jay M.; Vallières, Eric; Ding, Beiying; Johnson, Ann; Bhagwakar, Jan; Rashidi, Sanam; Zhu, Quing; Gitlitz, Barbara J.; Weksler, Benny; Costas, Kimberly; Altorki, Nasser K.

doi:10.1016/j.jtcvs.2023.01.012

Cited by 3 publications

(3 citation statements)

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“…Safety is another concern in the perioperative and long-term use of immunotherapy after surgery. The IMpower010 trial reported that Atezolizumab-related adverse events leading to hospitalization occurred in 7% of the surgery groups ( 34 ). In clinical practice, although the incidence of AEs in immunotherapy is often much lower than that in chemotherapy, immune related AEs (such as pneumonitis, myocarditis, etc.)…”

Section: Discussionmentioning

confidence: 99%

Perioperative immunotherapy for stage II-III non-small cell lung cancer: a meta-analysis base on randomized controlled trials

Yu,

Fu,

et al. 2024

Front. Oncol.

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BackgroundIn recent years, we have observed the pivotal role of immunotherapy in improving survival for patients with non-small cell lung cancer (NSCLC). However, the effectiveness of immunotherapy in the perioperative (neoadjuvant + adjuvant) treatment of resectable NSCLC remains uncertain. We conducted a comprehensive analysis of its antitumor efficacy and adverse effects (AEs) by pooling data from the KEYNOTE-671, NADIM II, and AEGEAN clinical trials.MethodsFor eligible studies, we searched seven databases. The randomized controlled trials (RCTs) pertaining to the comparative analysis of combination neoadjuvant platinum-based chemotherapy plus perioperative immunotherapy (PIO) versus perioperative placebo (PP) were included. Primary endpoints were overall survival (OS) and event-free survival (EFS). Secondary endpoints encompassed drug responses, AEs, and surgical outcomes.ResultsThree RCTs (KEYNOTE-671, NADIM II, and AEGEAN) were included in the final analysis. PIO group (neoadjuvant platinum-based chemotherapy plus perioperative immunotherapy) exhibited superior efficacy in OS (hazard ratio [HR]: 0.63 [0.49-0.81]), EFS (HR: 0.61 [0.52, 0.72]), objective response rate (risk ratio [RR]: 2.21 [1.91, 2.54]), pathological complete response (RR: 4.36 [3.04, 6.25]), major pathological response (RR: 2.79 [2.25, 3.46]), R0 resection rate (RR: 1.13 [1.00, 1.26]) and rate of adjuvant treatment (RR: 1.08 [1.01, 1.15]) compared with PP group (neoadjuvant platinum-based chemotherapy plus perioperative placebo). In the subgroup analysis, EFS tended to favor the PIO group in almost all subgroups. BMI (>25), T stage (IV), N stage (N1-N2) and pathological response (with pathological complete response) were favorable factors in the PIO group. In the safety assessment, the PIO group exhibited higher rates of serious AEs (28.96% vs. 23.51%) and AEs leading to treatment discontinuation (12.84% vs. 5.81%). Meanwhile, although total adverse events, grade 3-5 adverse events, and fatal adverse events tended to favor the PP group, the differences were not statistically significant.ConclusionPIO appears to be superior to PP for resectable stage II-III NSCLC, demonstrating enhanced survival and pathological responses. However, its elevated adverse event (AE) rate warrants careful consideration.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42023487475.

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Section: Discussionmentioning

confidence: 99%

Perioperative immunotherapy for stage II-III non-small cell lung cancer: a meta-analysis base on randomized controlled trials

Yu,

Fu,

et al. 2024

Front. Oncol.

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“…Cardiovascular Myocarditis (a) Pembrolizumab (<1%) [42][43][44] (a) Atezolizumab (1%-6.7%) 46,47 (a) IPI + NIVO (≤1%)…”

Section: Incidence Of Any-grade Iraes (%) Specific Iraes Pd-1 Inhibit...mentioning

confidence: 99%

“…Furthermore, patients on PD‐1 inhibitors have a notably higher rate of experiencing diarrhoea, skin rashes and kidney damage than those on PD‐L1 inhibitors. 37 , 38 , 39 , 40 , 41 Conversely, myocarditis is more common in patients undergoing treatment with anti‐PD‐L1 (1%–6.7%) compared to those on anti‐PD‐1 (<1%) 42 , 43 , 44 , 45 , 46 , 47 (Table 1 ).…”

Section: Clinical Manifestation Of Ici‐induced Iraes In Nsclcmentioning

confidence: 99%

Immune‐related adverse events in non‐small cell lung cancer: Occurrence, mechanisms and therapeutic strategies

Lin,

Xie,

Yao

et al. 2024

Clinical & Translational Med

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The emergence of immune checkpoint inhibitors (ICIs) has heralded a transformative era in the therapeutic landscape of non‐small cell lung cancer (NSCLC). While ICIs have demonstrated clinical efficacy in a portion of patients with NSCLC, these treatments concurrently precipitate a spectrum of immune‐related adverse events (irAEs), encompassing mild to severe manifestations, collectively posing a risk of significant organ damage. Consequently, there exists an imperative to augment our comprehension of the pathophysiological underpinnings of irAEs and to formulate more efficacious preventive and ameliorative strategies. In this comprehensive review, we delineate the clinical presentation of organ‐specific irAEs in patients with NSCLC and provide an in‐depth analysis of recent advancements in understanding the mechanisms driving ICI‐induced toxicity. Furthermore, we discuss potential strategies and targets for ameliorating these irAEs. Ultimately, this review aims to furnish valuable insights to guide further research endeavours in the context of irAEs in NSCLC patients.

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Commentary: Finding the balance: The role for adjuvant immunotherapy in the neoadjuvant era

Sachdeva

2023

The Journal of Thoracic and Cardiovascular Surgery

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Safety of adjuvant atezolizumab after pneumonectomy/bilobectomy in stage II-IIIA non–small cell lung cancer in the randomized phase III IMpower010 trial

Cited by 3 publications

References 30 publications

Perioperative immunotherapy for stage II-III non-small cell lung cancer: a meta-analysis base on randomized controlled trials

Perioperative immunotherapy for stage II-III non-small cell lung cancer: a meta-analysis base on randomized controlled trials

Immune‐related adverse events in non‐small cell lung cancer: Occurrence, mechanisms and therapeutic strategies

Commentary: Finding the balance: The role for adjuvant immunotherapy in the neoadjuvant era

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