Abstract 442: Pemetrexed and platinum plus pembrolizumab in patients with metastatic non-squamous non-small cell lung cancer by tumor burden at baseline: A post-hoc efficacy analysis of KEYNOTE-189

Abstract

Abstract Background: Pemetrexed (pem) and platinum (plat) plus pembrolizumab (pembro) showed clinical improvement in metastatic nonsquamous (NSQ) non-small-cell lung cancer (NSCLC). The aim of this analysis was to assess the clinical benefit of pem+plat+pembro in patients by tumor burden at baseline. Methods: The intention-to-treat population was analysed. Patients were randomized pem+plat+pembro (n=410) or pem+plat+placebo (n=206). The data cut-off date was May 20, 2019. OS, PFS, PFS-2, and ORR were evaluated by Kaplan-Meier and univariate Cox methods within subgroups identified by extent of distant metastasis (M1a vs. M1b), median number (≤3 vs. >3) of organ systems with lesions, and severity score of patient-reported symptoms (below median vs. above median) at baseline. These subgroup analyses were also replicated within PD-L1 TPS subgroups (<1%, 1-49%, ≥50%). Results: A consistent benefit in OS, PFS, PFS-2 and ORR was observed in the pem+plat+pembro treatment arm, compared to the pem+plat+placebo arm, irrespective of staging (M1a vs. M1b), number (≤ 3 vs. 3) of organ systems with lesions and severity of patient-reported symptoms (Table 1). Results by PD-L1 expression in the subgroups were generally consistent regardless of the level of expression. Conclusions: Pem+plat+pembro demonstrated consistent clinical benefit across all subgroups analysed regardless of baseline tumor burden. These results continue to support pem+plat+pembro as a standard of care in metastatic NSQ-NSCLC. TABLE 1.OS, PFS, PFS-2, and ORR in subgroups by tumor burden at baselineTreatment armsNaOSPFSPFS-2ORRHRHRHROdds ratioM1aPembro1230.540.480.572.66Placebo53M1bPembro2850.580.510.504.21Placebo152≤ 3b organ systems with lesionsPembro2350.490.410.436.00Placebo118> 3b organ systems with lesionsPembro1750.670.590.601.80Placebo88≤ medianc severity score of symptomsPembro1700.510.490.432.72Placebo82> medianc severity score of symptomsPembro1870.600.480.554.04Placebo97a.There were 3 patients with missing data for M1a and M1bb.Median number of organ systems with lesions was 3. Lesions include the primary tumorc.Median score = 122.2, based on six questions from the patient-reported LC-13 instrument Citation Format: Shirish Gadgeel, Jhanelle Grey, Maria Teresa Rizzo, Patrick Peterson, Jongseok Kim, Delvys Rodríguez-Abreu. Pemetrexed and platinum plus pembrolizumab in patients with metastatic non-squamous non-small cell lung cancer by tumor burden at baseline: A post-hoc efficacy analysis of KEYNOTE-189 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 442.