Association Between Immune-Related Adverse Events and Atezolizumab in Previously Treated Patients with Unresectable Advanced or Recurrent Non-Small Cell Lung Cancer

Overview

Journal Cancer Res Commun

Specialty Oncology

Date 2024 Oct 11

PMID 39392339

Authors

Hidetoshi Hayashi

Makoto Nishio

Hiroaki Akamatsu

Yasushi Goto

Satoru Miura

Akihiko Gemma

Ichiro Yoshino

Toshihiro Misumi

Takashi Kijima

Naoto Takase

Masaki Fujita

Sadatomo Tasaka

Atsuto Mouri

Tetsuro Kondo

Kei Takamura

Yosuke Kawashima

Kazuyoshi Imaizumi

Shunichiro Iwasawa

Shintaro Nakagawa

Tetsuya Mitsudomi

Affiliations

Soon will be listed here.

Abstract

Purpose: Real-world, large-scale studies on the association between immune-related adverse events (irAE) and immune checkpoint inhibitor therapy effectiveness are limited. We evaluated overall survival (OS) and progression-free survival based on the occurrence and grade of irAEs.

Patients And Methods: We used data from Japanese patients with unresectable advanced or recurrent non-small cell lung cancer (NSCLC) who received atezolizumab and were enrolled in J-TAIL, a multicenter, prospective, single-arm observational study.

Results: Among the 1,002 patients, 190 (19.0%) developed irAEs. The most common irAEs were skin disorders (3.8%) of any grade and interstitial lung disease (1.5%) of grade ≥3. Patients who developed irAEs within 4 or 6 weeks of treatment initiation had higher baseline C-reactive protein levels than those without irAEs. OS was longer in patients with irAEs [HR, 0.66; 95% confidence interval (CI), 0.54-0.82], particularly in those with low-grade irAEs (HR, 0.45; 95% CI, 0.33-0.62), than in patients without irAEs. The HR (95% CI) for OS in patients with low-grade and high-grade skin or endocrine disorder-related irAEs was 0.42 (0.28-0.64) and 0.37 (0.15-0.88), respectively. The HR (95% CI) for OS in patients with low-grade and high-grade irAEs other than skin or endocrine disorders was 0.44 (0.30-0.65) and 1.27 (0.96-1.69), respectively.

Conclusions: In patients with unresectable advanced or recurrent NSCLC treated with atezolizumab in real-world settings, irAEs are associated with a clinical benefit except in those with high-grade irAEs other than skin and endocrine disorders.

Significance: Immune checkpoint inhibitors are useful for treating NSCLC but can cause life-threatening irAEs. This study had a large sample size and stratified the analysis by irAE type and grade. The results suggest that improved management of irAEs may improve the therapeutic effect of atezolizumab.

Citing Articles

Organ-specific immune-related adverse events and prognosis in cancer patients receiving immune checkpoint inhibitors.

Han X, Chen Y, Xie H, Zhang Y, Cui Y, Guan Y BMC Cancer. 2025; 25(1):139.

PMID: 39856626 PMC: 11761211. DOI: 10.1186/s12885-025-13566-6.

References

Toi Y, Sugawara S, Kawashima Y, Aiba T, Kawana S, Saito R . Association of Immune-Related Adverse Events with Clinical Benefit in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Nivolumab. Oncologist. 2018; 23(11):1358-1365. PMC: 6291330. DOI: 10.1634/theoncologist.2017-0384. View

Watson A, Goutam S, Stukalin I, Ewanchuk B, Sander M, Meyers D . Association of Immune-Related Adverse Events, Hospitalization, and Therapy Resumption With Survival Among Patients With Metastatic Melanoma Receiving Single-Agent or Combination Immunotherapy. JAMA Netw Open. 2022; 5(12):e2245596. PMC: 9856439. DOI: 10.1001/jamanetworkopen.2022.45596. View

Boutros C, Tarhini A, Routier E, Lambotte O, Leroy Ladurie F, Carbonnel F . Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Nat Rev Clin Oncol. 2016; 13(8):473-86. DOI: 10.1038/nrclinonc.2016.58. View

Reck M, Rodriguez-Abreu D, Robinson A, Hui R, Csoszi T, Fulop A . Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016; 375(19):1823-1833. DOI: 10.1056/NEJMoa1606774. View

Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J . Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2016; 389(10066):255-265. PMC: 6886121. DOI: 10.1016/S0140-6736(16)32517-X. View

Schneider B, Naidoo J, Santomasso B, Lacchetti C, Adkins S, Anadkat M . Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update. J Clin Oncol. 2021; 39(36):4073-4126. DOI: 10.1200/JCO.21.01440. View

Kim H, Kim M, Lee S, Park S, Kim Y, Kim H . Development of thyroid dysfunction is associated with clinical response to PD-1 blockade treatment in patients with advanced non-small cell lung cancer. Oncoimmunology. 2018; 7(1):e1375642. PMC: 5739550. DOI: 10.1080/2162402X.2017.1375642. View

Haanen J, Obeid M, Spain L, Carbonnel F, Wang Y, Robert C . Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022; 33(12):1217-1238. DOI: 10.1016/j.annonc.2022.10.001. View

Pillai R, Behera M, Owonikoko T, Kamphorst A, Pakkala S, Belani C . Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: A systematic analysis of the literature. Cancer. 2017; 124(2):271-277. PMC: 5761314. DOI: 10.1002/cncr.31043. View

10.

Ali O, Diem S, Markert E, Jochum W, Kerl K, French L . Characterization of nivolumab-associated skin reactions in patients with metastatic non-small cell lung cancer. Oncoimmunology. 2016; 5(11):e1231292. PMC: 5139632. DOI: 10.1080/2162402X.2016.1231292. View

11.

Keenan T, Burke K, Van Allen E . Genomic correlates of response to immune checkpoint blockade. Nat Med. 2019; 25(3):389-402. PMC: 6599710. DOI: 10.1038/s41591-019-0382-x. View

12.

Lisberg A, Tucker D, Goldman J, Wolf B, Carroll J, Hardy A . Treatment-Related Adverse Events Predict Improved Clinical Outcome in NSCLC Patients on KEYNOTE-001 at a Single Center. Cancer Immunol Res. 2018; 6(3):288-294. PMC: 6066474. DOI: 10.1158/2326-6066.CIR-17-0063. View

13.

Iivanainen S, Ahvonen J, Aija Knuuttila , Tiainen S, Koivunen J . Elevated CRP levels indicate poor progression-free and overall survival on cancer patients treated with PD-1 inhibitors. ESMO Open. 2019; 4(4):e000531. PMC: 6735669. DOI: 10.1136/esmoopen-2019-000531. View

14.

Hua C, Boussemart L, Mateus C, Routier E, Boutros C, Cazenave H . Association of Vitiligo With Tumor Response in Patients With Metastatic Melanoma Treated With Pembrolizumab. JAMA Dermatol. 2015; 152(1):45-51. DOI: 10.1001/jamadermatol.2015.2707. View

15.

Weber J, Yang J, Atkins M, Disis M . Toxicities of Immunotherapy for the Practitioner. J Clin Oncol. 2015; 33(18):2092-9. PMC: 4881375. DOI: 10.1200/JCO.2014.60.0379. View

16.

Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2008; 45(2):228-47. DOI: 10.1016/j.ejca.2008.10.026. View

17.

Teraoka S, Fujimoto D, Morimoto T, Kawachi H, Ito M, Sato Y . Early Immune-Related Adverse Events and Association with Outcome in Advanced Non-Small Cell Lung Cancer Patients Treated with Nivolumab: A Prospective Cohort Study. J Thorac Oncol. 2017; 12(12):1798-1805. DOI: 10.1016/j.jtho.2017.08.022. View

18.

Mezquita L, Auclin E, Ferrara R, Charrier M, Remon J, Planchard D . Association of the Lung Immune Prognostic Index With Immune Checkpoint Inhibitor Outcomes in Patients With Advanced Non-Small Cell Lung Cancer. JAMA Oncol. 2018; 4(3):351-357. PMC: 5885829. DOI: 10.1001/jamaoncol.2017.4771. View

19.

Friedman C, Proverbs-Singh T, Postow M . Treatment of the Immune-Related Adverse Effects of Immune Checkpoint Inhibitors: A Review. JAMA Oncol. 2016; 2(10):1346-1353. DOI: 10.1001/jamaoncol.2016.1051. View

20.

Haanen J, Ernstoff M, Wang Y, Menzies A, Puzanov I, Grivas P . Rechallenge patients with immune checkpoint inhibitors following severe immune-related adverse events: review of the literature and suggested prophylactic strategy. J Immunother Cancer. 2020; 8(1). PMC: 7295425. DOI: 10.1136/jitc-2020-000604. View