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

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. 1030 out of 5357 (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 three, six, 12 and 18 months) and OS (at six, 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.

Clinical Effectiveness of Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer with a Poor Performance Status

“…A poor PS remains a strong prognostic factor for ICIs, as described in prospective and retrospective studies. Recently, Facchinetti et al reported a systematic review and metaanalysis of the clinical usefulness of first-line immunotherapy in NSCLC patients with a poor PS [16]. In their systematic review, 41 studies were chosen, and 1030 of 5357 (19%) of the patients in 30 studies on first-line pembrolizumab presented with an ECOG PS of 2-4 at pembrolizumab initiation.…”

Pembrolizumab monotherapy for untreated PD-L1-Positive non-small cell lung cancer in the elderly or those with poor performance status: A prospective observational study

“…However, there is a lack of real-world data from prospective observational studies examining first-line pembrolizumab monotherapy in patients with advanced NSCLC who are unfit for clinical trials, such as those with poor PS and elderly patients. Facchinetti et al reported in their meta-analysis of first-line immunotherapy for NSCLC patients with poor PS that prospective evidence supporting the role of immunotherapy in this population is limited, and clinical efforts are needed to improve prognosis, including the definition and factors contributing to poor PS and the development of dedicated treatment strategies (13).…”

Prognostic significance of tumor infiltrating lymphocytes on first-line pembrolizumab efficacy in advanced non-small cell lung cancer

“…By a recent meta-analysis, first-line ICIs in NSCLC patients with poor PS were described to be associated with worse outcome [ 11 , 12 ]. As our study indicated that low numbers of stromal CD4 TILs was closely related to poor PS, the degree of CD4 + T cell infiltration into the stroma may affect the patient’s general condition.…”