Treatment Options for Advanced Non-Small Cell Lung Cancer After Failure of Previous Immune Checkpoint Inhibitors and Chemotherapy: Meta-Analysis of Five Randomized Controlled Trials

Overview

Journal Curr Oncol

Publisher MDPI

Date 2025 Jan 24

PMID 39851962

Authors

Andrea Messori

Andrea Ossato

Lorenzo Gasperoni

Luna Del Bono

Alessandro Inno

Vera Damuzzo

Affiliations

Soon will be listed here.

Abstract

Background: Immune checkpoint inhibitors (ICIs), either alone or in combination with platinum-based chemotherapy, are effective in the first-line treatment of metastatic, non-oncogene-addicted, non-small cell lung cancer (NSCLC). However, when NSCLC patients progress, the efficacy of available treatment options is limited.

Methods: We undertook a meta-analysis that compared combination regimens with the current standard of care. Only randomized controlled trials (RCTs) were included (endpoint, overall survival [OS]). Our analysis used an artificial intelligence software program that reconstructs individual patient data from Kaplan-Meier curves. Hazard ratio (HR) with 95% confidence interval (CI) was the main parameter. Heterogeneity was based on Wald's test and likelihood ratio test.

Results: Five RCTs were included, whose experimental arms included five different combinations. In our analysis, these combination regimes showed no OS benefit compared to chemotherapy (HR = 1.066, 95%CI, 0.9311 to 1.221; = 0.35). Among the five control arms, cross-trial heterogeneity was remarkably low (likelihood ratio test = 3.76 on 4 df, = 0.40; Wald test = 3.83 on 4 df, = 0.40.

Discussion: In conclusion, five new second-line combination treatments for patients with NSCLC were not found to determine any benefit in terms of OS in comparison with the current standard of care.

References

Socinski M, Jotte R, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N . Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. N Engl J Med. 2018; 378(24):2288-2301. DOI: 10.1056/NEJMoa1716948. View

Zhou S, Yang H . Immunotherapy resistance in non-small-cell lung cancer: From mechanism to clinical strategies. Front Immunol. 2023; 14:1129465. PMC: 10115980. DOI: 10.3389/fimmu.2023.1129465. View

Pons-Tostivint E, Ezzedine R, Goronflot T, Crequit P, Chatellier T, Raimbourg J . Second-line treatment outcomes after first-line chemotherapy plus immunotherapy in Extensive-Stage small cell lung cancer (ES-SCLC) patients: A large French multicenter study. Lung Cancer. 2024; 194:107887. DOI: 10.1016/j.lungcan.2024.107887. View

Gogishvili M, Melkadze T, Makharadze T, Giorgadze D, Dvorkin M, Penkov K . Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial. Nat Med. 2022; 28(11):2374-2380. PMC: 9671806. DOI: 10.1038/s41591-022-01977-y. View

Paz-Ares L, Goto Y, Lim D, Halmos B, Cho B, Cobo M . Canakinumab in combination with docetaxel compared with docetaxel alone for the treatment of advanced non-small cell lung cancer following platinum-based doublet chemotherapy and immunotherapy (CANOPY-2): A multicenter, randomized, double-blind,.... Lung Cancer. 2024; 189:107451. DOI: 10.1016/j.lungcan.2023.107451. View

Ozguroglu M, Kilickap S, Sezer A, Gumus M, Bondarenko I, Gogishvili M . First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a mutlicentre, open-label, randomised, phase 3.... Lancet Oncol. 2023; 24(9):989-1001. DOI: 10.1016/S1470-2045(23)00329-7. View

Garon E, Ciuleanu T, Arrieta O, Prabhash K, Syrigos K, Goksel T . Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014; 384(9944):665-73. DOI: 10.1016/S0140-6736(14)60845-X. View

Jung H, Park S, Choi Y, Lee S, Ahn J, Ahn M . Continuation of Pembrolizumab with Additional Chemotherapy after Progression with PD-1/PD-L1 Inhibitor Monotherapy in Patients with Advanced NSCLC: A Randomized, Placebo-Controlled Phase II Study. Clin Cancer Res. 2022; 28(11):2321-2328. PMC: 9359724. DOI: 10.1158/1078-0432.CCR-21-3646. View

Reck M, Rodriguez-Abreu D, Robinson A, Hui R, Csoszi T, Fulop A . Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50. J Clin Oncol. 2021; 39(21):2339-2349. PMC: 8280089. DOI: 10.1200/JCO.21.00174. View

10.

Wang K, Fu Z, Sun G, Ran Y, Lv N, Wang E . Systemic treatment options for non-small cell lung cancer after failure of previous immune checkpoint inhibitors: a bayesian network meta-analysis based on randomized controlled trials. BMC Immunol. 2024; 25(1):37. PMC: 11212373. DOI: 10.1186/s12865-024-00633-z. View

11.

Paz-Ares L, Ciuleanu T, Cobo M, Schenker M, Zurawski B, Menezes J . First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021; 22(2):198-211. DOI: 10.1016/S1470-2045(20)30641-0. View

12.

Ahn M, Tanaka K, Paz-Ares L, Cornelissen R, Girard N, Pons-Tostivint E . Datopotamab Deruxtecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer: The Randomized, Open-Label Phase III TROPION-Lung01 Study. J Clin Oncol. 2024; 43(3):260-272. PMC: 11771353. DOI: 10.1200/JCO-24-01544. View

13.

Borghaei H, de Marinis F, Dumoulin D, Reynolds C, Theelen W, Percent I . SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. Ann Oncol. 2023; 35(1):66-76. DOI: 10.1016/j.annonc.2023.10.004. View

14.

Reckamp K, Redman M, Dragnev K, Minichiello K, Villaruz L, Faller B . Phase II Randomized Study of Ramucirumab and Pembrolizumab Versus Standard of Care in Advanced Non-Small-Cell Lung Cancer Previously Treated With Immunotherapy-Lung-MAP S1800A. J Clin Oncol. 2022; 40(21):2295-2306. PMC: 9287284. DOI: 10.1200/JCO.22.00912. View

15.

Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gumus M, Mazieres J . Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018; 379(21):2040-2051. DOI: 10.1056/NEJMoa1810865. View

16.

Schiller J, Harrington D, Belani C, Langer C, Sandler A, Krook J . Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002; 346(2):92-8. DOI: 10.1056/NEJMoa011954. View

17.

Liberati A, Altman D, Tetzlaff J, Mulrow C, Gotzsche P, Ioannidis J . The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med. 2009; 151(4):W65-94. DOI: 10.7326/0003-4819-151-4-200908180-00136. View

18.

Liu N, Zhou Y, Lee J . IPDfromKM: reconstruct individual patient data from published Kaplan-Meier survival curves. BMC Med Res Methodol. 2021; 21(1):111. PMC: 8168323. DOI: 10.1186/s12874-021-01308-8. View

19.

Hendriks L, Kerr K, Menis J, Mok T, Nestle U, Passaro A . Non-oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023; 34(4):358-376. DOI: 10.1016/j.annonc.2022.12.013. View

20.

Mountzios G, Naidoo J, Wang C, Creelan B, Trotier D, Campbell T . Beyond Chemoimmunotherapy in Advanced Non-Small Cell Lung Cancer: New Frontiers, New Challenges. Am Soc Clin Oncol Educ Book. 2024; 44(3):e432526. DOI: 10.1200/EDBK_432526. View