Abstract CT104: Efficacy of pembrolizumab (MK-3475) and relationship with PD-L1 expression in patients with non-small cell lung cancer: Findings from KEYNOTE-001)
Authors: Garon Edward B. , Rizvi Naiyer , Hui Rina , Leighl Natasha B. , Balmanoukian Ani S. , Eder Joseph P. , Patnaik Amita , Aggarwal Charu , Gubens Matthew A. , Horn Leora , Carcereny Enric , Ahn Myung-Ju , Felip Enriqueta , Lee Jong-Seok , Zhang Jin , Rangwala Reshma A. , Lubiniecki Gregory M. , Roach Charlotte M. , Emancipator Kenneth , Gandhi Leena 
Published: August 2015

Abstract
Background: Preliminary KEYNOTE-001 data showed that the PD-1 inhibitor pembro has manageable safety and antitumor activity in previously treated and treatment-naive advanced non-small cell lung cancer (NSCLC). In a training set of 182 pts, 129 of whom had measurable disease and tumor evaluable by an IHC clinical trial assay (CTA) for PD-L1 expression, ORR was higher in pts with membranous PD-L1 expression in ≥50% of tumor cells (proportion score [PS] ≥50%) vs PS &lt;50%. We aimed to verify the relationship between PD-L1 expression and ORR in an independent validation set of NSCLC pts enrolled in KEYNOTE-001 and to assess the impact of PD-L1 expression in the combined training and validation sets.
Methods: Advanced or metastatic NSCLC pts received pembro 2 mg/kg Q3W, 10 mg/kg Q3W, or 10 mg/kg Q2W. Response was assessed every 9 wk. Treatment decisions were managed per investigator-assessed irRC. Efficacy evaluation was per centrally assessed RECIST v1.1. PD-L1 expression was determined by the CTA. Before analysis, ORR and PD-L1 data from the validation set were merged in pts with measurable disease and CTA-evaluable tumors. Duration of response (DOR), PFS, and OS were assessed in all treated pts from the training and validation sets with CTA-evaluable tumors.
Results: In all 495 pts from the training and validation sets, irrespective of PD-L1 expression, ORR was 19.4%, median DOR was 12.4 mo, median PFS was 3.7 mo, and median OS was 12.0 mo. 9% experienced grade 3-5 treatment-related AEs; 4% discontinued due to a treatment-related AE. There was 1 treatment-related death (pneumonitis). Of the 313 pts in the validation set, ORR in the 204 pts evaluable by the CTA was 45.2% in those with PS ≥50% (Table). The relationship between ORR and PD-L1 expression was observed in previously treated and treatment-naive pts (Table). In the 356 pts evaluable by the CTA in the total population, PFS and OS were longer in pts with PS ≥50% (Table). Median OS was not reached in pts with PS ≥50%, regardless of prior treatment. Median (range) DOR was similar in pts with PS ≥50% (12.4 mo [2+ to 22.8+]), 1-49% (10.3 mo [1.4+ to 10.3]), and &lt;1% (NR [0.9+ to 10.8+]).
Conclusion: Pembro provides durable antitumor efficacy and safety in pts with treatment-naive and previously treated NSCLC. These data validate that membranous PD-L1 expression in ≥50% of tumor cells identifies pts with advanced NSCLC who are particularly likely to obtain clinical benefit from pembro.
Proportion Score (PS)≥50%1-49%&lt;1%ORR in evaluable pts in the validation set,% (95% CI)Totaln = 73n = 103n = 2845.2 (33.5-57.3)16.5 (9.9-25.1)10.7 (2.3-28.2)Previously treatedn = 57n = 77n = 2243.9 (30.7-57.6)15.6 (8.3-25.6)9.1 (1.1-29.2)Treatment naiven = 16n = 26n = 650.0 (24.7-75.3)19.2 (6.6-39.4)16.7 (0.4-64.1)Survival in evaluable pts in the total population, mo, median (95% CI)PFSTotaln = 119n = 161n = 766.3 (2.9-12.5)3.3 (2.1-4.1)2.3 (2.1-4.0)Previously treatedn = 99n = 127n = 686.1 (2.1-12.5)2.3 (2.1-3.4)2.2 (2.0-4.1)Treatment naiven = 20n = 34n = 812.5 (2.4-12.5)4.3 (3.1-6.4)3.5 (2.1-4.2)OS [NR, not reached.]Totaln = 119n = 161n = 76NR (13.7-NR)8.8 (6.8-12.4)8.8 (5.5-12.0)Previously treatedn = 99n = 127n = 68NR (9.3-NR)7.3 (5.8-12.1)8.6 (5.5-12.0)Treatment naiven = 20n = 34n = 8NR (NR-NR)16.2 (8.6-16.2)10.4 (3.4-NR)
Citation Format: Edward B. Garon, Naiyer Rizvi, Rina Hui, Natasha B. Leighl, Ani S. Balmanoukian, Joseph P. Eder, Amita Patnaik, Charu Aggarwal, Matthew A. Gubens, Leora Horn, Enric Carcereny, Myung-Ju Ahn, Enriqueta Felip, Jong-Seok Lee, Jin Zhang, Reshma A. Rangwala, Gregory M. Lubiniecki, Charlotte M. Roach, Kenneth Emancipator, Leena Gandhi. Efficacy of pembrolizumab (MK-3475) and relationship with PD-L1 expression in patients with non-small cell lung cancer: Findings from KEYNOTE-001). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT104. doi:10.1158/1538-7445.AM2015-CT104