Effectiveness and safety of immunotherapy in NSCLC patients with ECOG PS score ≥2 - Systematic review and meta-analysis

Bartłomiej Tomasik; Michał Bieńkowski; Marcin Braun; Sanjay Popat; Rafał Dziadziuszko

doi:10.1016/j.lungcan.2021.06.004

Effectiveness and safety of immunotherapy in NSCLC patients with ECOG PS score ≥2 - Systematic review and meta-analysis

Lung Cancer. 2021 Aug:158:97-106. doi: 10.1016/j.lungcan.2021.06.004. Epub 2021 Jun 6.

Authors

Bartłomiej Tomasik¹, Michał Bieńkowski², Marcin Braun³, Sanjay Popat⁴, Rafał Dziadziuszko⁵

Affiliations

¹ Department of Biostatistics and Translational Medicine, Medical University of Łódź, 15 Mazowiecka Street, 92-215 Łódź, Poland; Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
² Department of Pathomorphology, Medical University of Gdańsk, 17 Smoluchowskiego Street, 80-214 Gdańsk, Poland.
³ Department of Pathology, Chair of Oncology, Medical University of Łódź, Pomorska 251 Street, 92-213 Łódź, Poland.
⁴ Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK; The Institute of Cancer Research, 123 Old Brompton Road, London SW7 3RP, UK; National Hearth and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK.
⁵ Department of Oncology and Radiotherapy, Medical University of Gdańsk, 7 Debinki Street, 80-211 Gdańsk, Poland. Electronic address: rafald@gumed.edu.pl.

PMID: 34144405
DOI: 10.1016/j.lungcan.2021.06.004

Abstract

Background: Immune checkpoint inhibitors (ICIs) are standard of care in advanced non-small cell lung cancer (NSCLC), however their status in patients with poor performance status (PS) is poorly defined. We aimed to evaluate the efficacy and safety of ICIs in NSCLC patients with PS ≥ 2.

Methods: We conducted a systematic review and meta-analysis of interventional and observational studies, which reported efficacy and safety data on ICIs in PS ≥ 2 comparing to PS ≤ 1 NSCLC patients. Efficacy endpoints included: Objective Response Rate (ORR), Disease-Control Rate (DCR), Overall Survival (OS), Progression-Free Survival (PFS). Safety endpoint was the incidence of severe (grade≥3) Adverse Events (AE). Random-effects model was applied for meta-analysis. Heterogeneity was assessed using I². The review is registered on PROSPERO (CRD42020162668).

Findings: Sixty-seven studies (n = 26,442 patients) were included. In PS ≥ 2 vs. PS ≤ 1 patients, the pooled odds ratios were: for ORR 0.46 (95 %CI: 0.39-0.54, I²:0 %); for DCR 0.39 (95 %CI: 0.33-0.48, I²:50 %) and for AEs 1.12 (95 %CI: 0.84-1.48, I²:39 %). The pooled hazard ratio for PFS was 2.17 (95 %CI: 1.96-2.39, I²:65 %) and for OS was 2.76 (95 %CI: 2.43-3.14, I²:76 %). The safety profile was comparable regardless of the PS status.

Interpretation: Patients with impaired PS status are, on average, twice less likely to achieve a response when exposed to ICIs when compared with representative PS ≤ 1 population. For lung cancer patients treated with ICIs, the impaired PS is not only prognostic, but also predictive for response, while the safety profile is not affected. Prospective randomized studies are indispensable to determine whether poor PS patients derive benefit from ICIs.

Keywords: Effectiveness and safety; Immunotherapy; Meta-analysis; Non-small cell lung cancer; Performance status.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Carcinoma, Non-Small-Cell Lung* / drug therapy
Humans
Immunotherapy
Lung Neoplasms* / drug therapy
Progression-Free Survival
Prospective Studies