First-line immunotherapy in advanced non-small-cell lung cancer patients with ECOG performance status 2: results of an International Expert Panel Meeting by the Italian Association of Thoracic Oncology

Abstract

Background Immunotherapy represents the standard of care in the first-line treatment of advanced non-small-cell lung cancer (NSCLC), either as monotherapy in high programmed death-ligand 1 (PD-L1)-positive tumors (≥50%) or in combination with platinum-based chemotherapy regardless of PD-L1 status. However, most pivotal clinical trials of immune checkpoint inhibitors (ICIs) did not include patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2. Hence, a consensus is lacking on the safety and efficacy of ICIs in this specific subgroup of patients. Materials and methods A virtual International Expert Panel took place in July 2021 with the aim of reviewing the available evidence on the use of ICIs in NSCLC patients with ECOG PS 2, both in clinical practice and in a research setting. Results All panelists expressed concern about the applicability of currently available PS scales to evaluate patients for ICI treatment. The panelists agreed that, though limited, the available data support the safety of single-agent immunotherapy in PS 2 NSCLC patients, whereas concern was raised on the safety of ICI combinations, mainly related to chemotherapy and/or anti-cytotoxic T-lymphocyte-associated antigen 4 toxicity. On the basis of reviewed data, ICI efficacy may be speculated in PS 2 NSCLC patients; however, PS 2 remains a negative prognostic category as compared to PS 0-1 in patients treated with ICI, as it is for chemotherapy. The panelists defined high, medium and low priorities in clinical research. High priority was attributed to the inclusion of PS 2 patients in prospective clinical trials and the specific evaluation of combined ICI treatments with attenuated chemotherapy doses. Conclusions Based on the current evidence, the panelists outlined the major limitations affecting PS 2 patients with NSCLC and reached common considerations on the feasibility, safety and effectiveness of ICI monotherapy and ICI combinations in the first-line setting.

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

“…Recently, the results of an International Expert Panel Meeting supported the safety of immunotherapy, but not immunochemotherapy, in NSCLC patients with PS 2, based on clinical evidence (24). In the KEYNOTE-042 study, irAEs were reported to be 63% at any grade and 18% at grade 3 or higher in the pembrolizumab group of NSCLC patients with good PS (5).…”

Quality of life in patients with non-small cell lung cancer treated with PD-1/PD-L1 inhibitors: a systematic review and meta-analysis

“…Lastly, despite questionnaires reporting quality of life are currently considered to be of high quality, there are currently no international guidelines for statistical analysis of QOL in cancer patients using ICIs, and there is still a lack of confirmation of research hypotheses and questionnaires in cancer patients treated with ICIs in methodological aspects [ 33 ]. ECOG PS ≥ 2 was almost excluded from clinical trials, and future studies should be focused on older and weak patients [ 34 , 35 ].…”

Real-world eligibility for platinum doublet plus immune checkpoint inhibitors in extensive-stage small-cell lung cancer

“…Over half of our real-world ES PS population had an ECOG PS of ≥2 at diagnosis. While chemotherapy and ICI treatments have been widely used in good PS patients with lung cancer, due to the evidence in NSCLC, the feasibility is much less clear in PS 2 patients and is not currently informed by randomized clinical trials ( 16 ). A prospective randomized phase II clinical trial of ICIs with or without carboplatin and paclitaxel in advanced NSCLC with PS 2 is yet to be reported ( 17 ).…”