A Real-World Study on the Effectiveness and Safety of Pembrolizumab Plus Chemotherapy for Nonsquamous NSCLC

Abstract

Introduction The real-world effectiveness of combination treatment with cytotoxic chemotherapy and programmed cell death protein-1 or programmed death-ligand 1 inhibitor for NSCLC, especially for the elderly (aged ≥75 y) or those with poor performance status (≥2), has not been fully elucidated. We investigated the real-world effectiveness and safety of this combination therapy in these populations. Methods This multicenter retrospective study evaluated patients who are chemo-naïve with advanced NSCLC who received a combination of platinum, pemetrexed, and pembrolizumab between December 2018 and June 2019. This was an updated prespecified secondary analysis with the primary objective of investigating the safety and effectiveness in this cohort. Results Overall, 299 patients were included. Multivariate analysis identified performance status (0–1) and programmed death-ligand 1 tumor proportion score (≥50%) as significant independent predictors of progression-free survival ( p = 0.007, and p = 0.003, respectively). The incidence of severe adverse events (AEs) was higher in the elderly and those with poor performance status than in their younger and good performance status counterparts. A total of 71 patients developed AEs that led to treatment discontinuation, and AE-related treatment discontinuation occurred at a significantly higher rate in older patients (median [range]) (70 [46–82] y) than in younger patients (68 [31–84] y) ( p <0.001). Conclusions Combination treatment with pembrolizumab plus chemotherapy had low real-world effectiveness for poor performance status patients. Severe AEs occurred at a higher rate in the elderly and poor performance status patients, and the AE-related treatment discontinuation rate increased with age. Physicians should be cautious about using this regimen, especially in the elderly and poor performance status patients.

Efficacy and Safety of Programmed Death-Ligand 1 Inhibitor Plus Platinum-Etoposide Chemotherapy in Patients With Extensive-Stage SCLC: A Prospective Observational Study

“…In patients with nonsquamous NSCLC, poor ECOG-PS has been found to be a poor prognostic factor in patients receiving pembrolizumab plus chemotherapy. 10 In a retrospective data analysis, chemotherapy plus atezolizumab for patients with ES-SCLC with a PS of more than or equal to 2 was reported to be feasible; however, the OS was short, which is consistent with our present observations. 23 …”

“… 5 , 6 , 7 , 8 Nevertheless, elderly (≥75 y old) patients with NSCLC tended to have higher rates of treatment discontinuation owing to adverse events (AEs) and severe AEs, including pneumonitis. 9 , 10 …”

The use of immunotherapy in older patients with advanced non-small cell lung cancer

“…Most patient had adenocarcinoma, were tobacco smokers, and had an ECOG PS 0 to 1. No difference in OS and PFS was found between patients > 75 and < 75, but after stratifying patients by age groups (<65, 65 to 74, ≥ 75) a trend of increased rates of severe AEs (16%, 21%, and 26%, respectively) and treatment discontinuation due to AEs (14%, 27%, and 40%, respectively) was observed [63].…”

“…A recently published multicenter retrospective cohort study reported of 299 patients with treatment-naïve NSCLC who received platinum, pemetrexed and pembrolizumab [63]. The median age was 68; 43 elderly patients (14%) were included.…”

“…A high pretreatment SIP (> 39.5% SIP+ cells) was shown to be associated with reduced activity and efficacy (ORR, PFS and OS) of single agent ICBs [82]. Interestingly, baseline SIP status was not significantly associated with age (SIP+ patients had a median age of 68 years [59-73.5] vs. 61.5 years [54][55][56][57][58][59][60][61][62][63][64][65][66][67] in SIP-) [82]. Similarly, > 13% of peripheral blood CD8 EM1 cells (CD27 + CD28 + ) at baseline was found to positively correlate with OS among 137 patients with metastatic melanoma, while the frequency of CD8 EMRA (T cells with terminally differentiated phenotype, CD45RA + CCR7 − CD27 − CD28 − ) showed a negative association [83].…”