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. 2021 Jun;10(6):2917-2936.
doi: 10.21037/tlcr-21-15.

First-line immunotherapy in non-small cell lung cancer patients with poor performance status: a systematic review and meta-analysis

Francesco Facchinetti  1 , Massimo Di Maio  2 , Fabiana Perrone  3 , Marcello Tiseo  3   4
Affiliations

First-line immunotherapy in non-small cell lung cancer patients with poor performance status: a systematic review and meta-analysis

Francesco Facchinetti et al. Transl Lung Cancer Res. 2021 Jun.

Abstract

Background: Immune checkpoint inhibitors (ICIs) have become the standard of care for the first-line treatment of advanced non-small cell lung cancer patients (NSCLC), either as single agents or combined with chemotherapy. The evidence sustaining their role for poor performance status (ECOG PS ≥2) patients is limited.

Methods: We search PubMed and the proceedings of international oncology meetings to perform a systematic review to assess the outcomes poor PS NSCLC patients who received ICIs as first-line treatment. A meta-analysis included retrospective studies focusing on pembrolizumab monotherapy in PD-L1 ≥50% NSCLC. We reported the global objective response rate (ORR), disease control rate (DCR) and landmark progression-free and overall survival (PFS and OS, respectively) in ECOG PS ≥2 and 0-1 patients, respectively.

Results: Forty-one studies were included in the systematic review. Thirty-two retrospective studies focused on pembrolizumab monotherapy in PD-L1 ≥50% cases. In total, 1,030 out of 5,357 (19%) of patients across 30 studies presented with a PS ≥2 at pembrolizumab initiation. In 18 studies with detailed clinical information, worse outcomes in poor PS compared to good PS patients were documented. The meta-analysis revealed that ORR and DCR within the PS ≥2 patient population were 30.9% and 41.5% respectively (55.2% and 71.5% in PS 0-1 patients). The rates of PFS (at 3, 6, 12 and 18 months) and OS (at 6, 12, 18 and 24 months) were approximately double in the good PS compared to the poor PS group of patients. In the three prospective trials where of ICIs in PS 2 populations, the diverse strictness in PS definition likely contributed to the differential outcomes observed. Six retrospective studies dealt with chemo-immunotherapy combinations.

Conclusions: Still with limited prospective evidence sustaining the role of immunotherapy in previously untreated NSCLC with poor PS, 19% of patients in retrospective series dealing with pembrolizumab in PD-L1 ≥50% tumors had an ECOG PS ≥2. Clinical effort encompassing the definition of poor PS, of the factors conditioning it, and the development of dedicated treatment strategies is required to improve the outcomes in this patient population.

Keywords: ECOG PS 2; Non-small cell lung cancer (NSCLC); PD-1; PD-L1; immune checkpoint inhibitors (ICIs); pembrolizumab.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-21-15). The series “Immunotherapy in other thoracic malignancies and uncommon populations” was commissioned by the editorial office without any funding or sponsorship. MT serves as an unpaid editorial board member of Translational Lung Cancer Research from Dec 2014 to Nov 2021. FF reports personal fees from BMS, personal fees from Roche, outside the submitted work. MDM reports personal fees from Astra-Zeneca, personal fees from Pfizer, personal fees from BMS, personal fees from MSD, personal fees from Eisai, personal fees from Janssen, personal fees from Astellas, personal fees from Takeda, grants from Tesaro-GSK, outside the submitted work. MT reports grants and personal fees from Astra-Zeneca, grants and personal fees from Boehringer Ingelheim, grants from Pfizer, personal fees from Eli-Lilly, personal fees from BMS, grants and personal fees from Novartis, grants and personal fees from Roche, grants and personal fees from MSD, grants from Otsuka, grants from Pierre Fabre, outside the submitted work. The authors have no other conflicts of interest to declare.

Figures

Figure 1
Figure 1
PRISMA flow diagram describing the process leading to the identification of studies included in the systematic review and meta-analysis.
Figure 2
Figure 2
Meta-analysis of objective responses and disease control in patients with ECOG performance status ≥2 (poor PS) and 0-1 (good PS) receiving pembrolizumab in retrospective studies. ORR, objective response rate; DCR, disease control rate.
See this image and copyright information in PMC

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