2603 - Analysis of Efficacy Outcomes Based on Programmed Death Ligand 1 (PD-L1) Scoring Techniques in Patients With Head and Neck Squamous Cell Carcinoma (HNSCC) From KEYNOTE-040

Background

Two techniques are available for scoring programmed death ligand 1 (PD-L1) expression: tumor proportion score (TPS), which measures PD-L1 in tumor cells, and combined positive score (CPS), which measures PD-L1 in tumor and immune cells. The European Medicines Agency approved pembrolizumab for the second-line treatment of patients with HNSCC whose tumors express PD-L1 based on a TPS ≥50%. To determine whether CPS can be used interchangeably with TPS to evaluate patients with HNSCC for second-line therapy, a post hoc analysis from the open-label phase 3 KEYNOTE-040 (NCT02252042) trial was conducted.

Methods

Patients with platinum-refractory HNSCC received pembrolizumab (200 mg Q3W) or standard of care (SOC; chemotherapy or cetuximab). Tumor samples were collected during screening (up to 42 days before baseline) and were evaluated by TPS and CPS. Scoring methods were evaluated for efficacy outcomes, including objective response rate (RECIST v1.1), progression-free survival, and overall survival.

Results

Of 495 patients enrolled, 475 were assessed for PD-L1 expression per TPS and CPS. Efficacy results based on TPS and CPS cutpoints are summarized in the table. Concordance between TPS and CPS cutpoints was 77% at 1, 91% at 20, and 95% at 50.

Conclusions

At lower expression levels, CPS detects a larger fraction of responders than TPS while maintaining similar survival results. At higher expression levels, CPS ≥50 can be used interchangeably with TPS ≥50%. Thus, CPS is a valid scoring method for determining PD-L1 status in patients with HNSCC being evaluated for second-line treatment. Efficacy results demonstrating treatment benefit with pembrolizumab compared with SOC were similar regardless of scoring method used.

Clinical trial identification

NCT02252042.

Editorial acknowledgement

Holly C. Cappelli, PhD, and Dana Francis, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA), funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

E. Cohen: Advisory / Consultancy: Amgen, AstraZeneca, Bayer, BMS, Incyte, MSD, Merck. K. Harrington: Research grant / Funding (institution), For trial conduct: MSD, AstraZeneca, Amgen, BMS, Boehringer-Ingelheim, Merck-Serono, Pfizer, Replimune, Vyriad; Advisory / Consultancy: MSD, AstraZeneca, Amgen, BMS, Boehringer-Ingelheim, Merck-Serono, Pfizer, Replimune, Vyriad; Speaker Bureau / Expert testimony: MSD, AstraZeneca, Amgen, BMS, Merck-Serono; Honoraria (self): MSD, AstraZeneca, Amgen, BMS, Boehringer-Ingelheim, Merck-Serono, Pfizer, Replimune, Vyriad. D. Soulières: Research grant / Funding (institution), Trial conduct: MSD; Advisory / Consultancy: Merck, MSD; Speaker Bureau / Expert testimony: Merck, MSD. C. Le Tourneau: Advisory / Consultancy: MSD, BMS, Merck Serono, Amgen, Nanobiotix, AstraZeneca, Roche. L.F. Licitra: Honoraria (self): Eisai, BMS, MSD, Merck–Serono, Boehringer Ingelheim, Novartis, AstraZeneca, Roche, Bayer, Debiopharm, Sobi, Kura Oncology, Health & Life srl, Ipsen Innovation, Immuno-Oncology Hub, Incyte Biosciences Italy srl, Doxa Pharma srl, Amgen and Nanobiotics Sa.; Advisory / Consultancy, Research grant / Funding (institution): Bayer, GSK, MSD, Kura Oncology, Ipsen, Health & Life srl, Merck–Serono, Doxa Pharma srl.; Research grant / Funding (institution): Eisai, MSD, Merck–Serono, Boehringer Ingelheim, Novartis, AstraZeneca, Roche, BMS, Celgene International, Exelixis inc, Hoffmann-La roche ltd, IRX Therapeutics inc, Medpace inc and Pfizer.; Travel / Accommodation / Expenses: Merck–Serono, BMS, MSD, Debiopharm, Sobi, Bayer, Stilema, AccMed, Aiocc, Aiom. B. Burtness: Research grant / Funding (institution), For trial conduct: MSD, Boehringer-Ingelheim; Honoraria (self), For steering committee: MSD; Honoraria (self), Travel / Accommodation / Expenses, For steering committee and presentation of trial results: Boehringer-Ingelheim; Advisory / Consultancy: Amgen, Alligator Biosciences, Aduro; Honoraria (self), Advisory / Consultancy: Bayer, AstraZeneca, Cue Biosciences, BMS, Genentech/Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene, Debiopharm, Maverick Therapeutics, GSK; Honoraria (self), Data Safety Monitoring Commttee: VentiRx; Honoraria (self), Travel / Accommodation / Expenses, Data Safety Monitoring Committ: IDDI. T. Bal: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. J. Juco: Full / Part-time employment: Merck & Co., Inc.; Shareholder / Stockholder / Stock options: Merck & Co., Inc., Regeneron, Illumina. R.F. Swaby: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. K. Emancipator: Full / Part-time employment: Merck & Co., Inc.; Shareholder / Stockholder / Stock options: Merck & Co., Inc., Johnson & Johnson, Bayer AG, Celgene; Full / Part-time employment, Spouse: Celgene. All other authors have declared no conflicts of interest.