TPS8674 Background: Lung cancer disproportionately affects older adults, with 70% of cases diagnosed in patients ≥65 years old, though older adults are often underrepresented in clinical trials. 1,2 KEYNOTE-189 3 and KEYNOTE-407 4 studies established superiority of chemotherapy-immunotherapy (chemo-IO) compared to chemotherapy irrespective of PD-L1 tumor proportion score (TPS) in patients with ECOG PS 0-1. Single-agent pembrolizumab was also shown to be superior to chemotherapy based on KEYNOTE-024 5 and KEYNOTE-042 6 studies. KEYNOTE-189 3 /407 4 studies highlighted synergistic benefit from chemo-IO across TPS subsets while single-agent IO benefit is mostly in the TPS ≥50% population. It is unknown if single-agent IO versus chemo-IO is superior for patients with PD-L1 TPS 1-49%, especially in older adults. There is increased risk for toxicity for adults with co-morbidities and impaired function that is enriched along the age continuum. Use of single-agent IO may limit benefit from synergy. Alternatively, chemo may increase toxicity and adversely impact quality of life (QOL) and survival in older adults. The goal of this study is to evaluate overall survival (OS) in older adults with metastatic NSCLC, PD-L1 TPS 1-49% treated with first-line single-agent IO versus chemo-IO. Methods: This phase 3 study randomizes (1:1) patients age ≥70 years old with metastatic NSCLC, PD-L1 TPS 1-49% to treatment with pembrolizumab versus pembrolizumab plus chemotherapy with primary endpoint of OS. Patients undergo an abbreviated baseline geriatric assessment (GA) of function, nutrition, cognition, and QOL with opportunity for modification of chemotherapy regimen and dosing based on results. Patients are treated with 4 cycles of induction pembrolizumab 200 mg IV every 3 weeks (Arm A) or 4 cycles of induction pembrolizumab 200 mg IV every 3 weeks in combination with chemotherapy (Arm B). Chemotherapy is investigator-selected from platinum doublet (carboplatin/pemetrexed, carboplatin/paclitaxel, carboplatin/ nab -paclitaxel) or single-agent options (pemetrexed, paclitaxel, nab -paclitaxel) with dose attenuation per investigator discretion. Induction is followed by up to two years of maintenance pembrolizumab (200 mg IV every 3 weeks or 400 mg IV every 6 weeks) with option for continuing maintenance pemetrexed. Modified GA is repeated at specified time points. Optional stool studies are collected at baseline and after four cycles of therapy. Secondary endpoints include progression-free survival, objective response rate, tolerability and QOL. Exploratory aims evaluate GA metrics as predictors of clinical outcomes and relate gut microbe diversity and abundance to treatment outcomes. Efficacy analyses are conducted on an intention-to-treat basis. Enrollment is ongoing, and current accrual (as of January 6, 2026) is 22 of 304. Clinical trial information: NCT06096844 .
Baumgart et al. (Thu,) studied this question.