Correlations of response rate and progression-free survival with overall survival in immunotherapy trials for metastatic non-small-cell lung cancer: an FDA pooled analysis

Bernardo Haddock Lobo Goulart; Sirisha L Mushti; Somak Chatterjee; Erin Larkins; Pallavi S Mishra-Kalyani; Richard Pazdur; Paul G Kluetz; Harpreet Singh

doi:10.1016/S1470-2045(24)00040-8

Correlations of response rate and progression-free survival with overall survival in immunotherapy trials for metastatic non-small-cell lung cancer: an FDA pooled analysis

Lancet Oncol. 2024 Apr;25(4):455-462. doi: 10.1016/S1470-2045(24)00040-8. Epub 2024 Mar 5.

Authors

Bernardo Haddock Lobo Goulart¹, Sirisha L Mushti², Somak Chatterjee², Erin Larkins³, Pallavi S Mishra-Kalyani², Richard Pazdur⁴, Paul G Kluetz⁴, Harpreet Singh⁴

Affiliations

¹ Office of Oncologic Diseases, Food and Drug Administration, Silver Spring, MD, USA. Electronic address: bernardo.haddocklobogoulart@fda.hhs.gov.
² Office of Biostatistics, Food and Drug Administration, Silver Spring, MD, USA.
³ Office of Oncologic Diseases, Food and Drug Administration, Silver Spring, MD, USA.
⁴ Office of Oncologic Diseases, Food and Drug Administration, Silver Spring, MD, USA; Oncology Center of Excellence, Food and Drug Administration, Silver Spring, MD, USA.

PMID: 38458207
DOI: 10.1016/S1470-2045(24)00040-8

Abstract

Background: Radiographic changes might not fully capture the treatment effects of immune checkpoint inhibitors (ICIs). We aimed to assess correlations of overall response rate and progression-free survival with overall survival in trials of ICIs for metastatic non-small-cell lung cancer (NSCLC).

Methods: To assess trial-level and patient-level correlations of overall response rate and progression-free survival with overall survival, we conducted a pooled analysis of first-line randomised trials (including patients aged ≥18 years with metastatic squamous and non-squamous NSCLC and an Eastern Cooperative Oncology Group performance status of 0-1) submitted to the US Food and Drug Administration from June 24, 2016, to March 16, 2021. Eligible trials evaluated at least one ICI in the experimental group versus chemotherapy in the control group. At the trial level, we used weighted linear regression to derive coefficients of determination (R²). At the patient level, we used Cox proportional hazards models to compare overall survival between responders versus non-responders per Response Evaluation Criteria in Solid Tumours (version 1.1).

Findings: A total of 13 trials including 9285 patients evaluated ICIs alone or in combination with chemotherapy versus chemotherapy alone. At the trial level, the R² was 0·61 (95% CI 0·32-0·84) for correlation of overall response rate with overall survival and 0·70 (0·40-0·89) for correlation of progression-free survival with overall survival. Correlations ranged from weak to moderate when evaluating subgroups by PD-L1 expression and were consistent across trials evaluating ICIs alone or in combination with chemotherapy. At the patient level, responders had longer overall survival than non-responders (hazard ratio [HR] 0·28 [95% CI 0·26-0·30]). Among responders, overall survival was longer in patients enrolled in experimental groups than in control groups (HR 0·54 [95% CI 0·48-0·61]).

Interpretation: Correlations of overall response rate and progression-free survival with overall survival were generally moderate in this pooled analysis. The findings support routine analysis of mature overall survival data, where feasible, in first-line randomised trials of ICIs for metastatic NSCLC.

Funding: US Food and Drug Administration.

MeSH terms

Adolescent
Adult
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Carcinoma, Non-Small-Cell Lung* / drug therapy
Humans
Immunotherapy
Lung Neoplasms* / drug therapy
Progression-Free Survival