659MO - Pembrolizumab with or without chemotherapy for first-line treatment of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): 5-year results from KEYNOTE-048

Background

Long-term follow-up (4 years) of the phase 3 KEYNOTE-048 (NCT02358031) study continued to demonstrate survival benefit with pembrolizumab monotherapy and pembrolizumab + chemotherapy vs EXTREME in first-line R/M HNSCC. Pembrolizumab showed significantly longer OS vs EXTREME in PD-L1 CPS ≥1. Given that pembrolizumab + chemotherapy or pembrolizumab for CPS ≥1 is standard of care for first-line R/M HNSCC in the United States, outcomes with extended follow-up are of interest. We present 5 years of follow-up in all patients (pts) from KEYNOTE-048.

Methods

Pts with incurable R/M HNSCC of the oropharynx, oral cavity, hypopharynx, or larynx were randomly assigned 1:1:1 to pembrolizumab 200 mg Q3W, pembrolizumab + chemotherapy, or EXTREME. OS, PFS, ORR, and DOR were assessed in the ITT population and analyzed in PD-L1 CPS ≥1, PD-L1 CPS ≥20, and total populations.

Results

As of the February 21, 2022, data cutoff date, median follow-up was 69.2 mo (range, 61.2-81.6 mo) for pembrolizumab vs EXTREME and 68.6 mo (range, 61.2-82.1 mo) for pembrolizumab + chemotherapy vs EXTREME. The 5-year OS rate for pembrolizumab vs EXTREME was, respectively, 19.9% vs 7.4% in CPS ≥20, 15.4% vs 5.5% in CPS ≥1, and 14.4% vs 6.5% in total populations. The 5-year OS rate for pembrolizumab + chemotherapy vs EXTREME was, respectively, 23.9% vs 6.4% in CPS ≥20, 18.2% vs 4.3% in CPS ≥1, and 16.0% vs 5.2% in total populations. 5-yr OS and PFS rates, ORR, and DOR are shown in the table. Grade 3-5 treatment-related AEs were 17.0% for pembrolizumab, 71.7% for pembrolizumab + chemotherapy, and 69.3% for EXTREME.

Conclusions

With an extended follow-up of 5 years, first-line pembrolizumab and pembrolizumab + chemotherapy continued to show durable antitumor activity and manageable safety in R/M HNSCC. These results further support pembrolizumab and pembrolizumab + chemotherapy as first-line standard of care in R/M HNSCC. Table: 659MO

P, pembro; E, EXTREME; C, chemo

Clinical trial identification

NCT02358031, release date: February 6, 2015.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Mallory Campbell, PhD and Matthew Grzywacz, PhD of ApotheCom (Yardley, PA, USA).

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

M. Tahara: Financial Interests, Personal and Institutional, Advisory Board: Ono Pharmaceutical, MSD, Bayer, BMS, Merck Biopharma, Eisai, Pfizer, Loxo, Celgene, Rakuten Medical, Amgen, Novartis; Financial Interests, Personal and Institutional, Principal Investigator: Ono Pharmaceutical, MSD, Bayer, BMS, Merck Biopharma, Eisai, Pfizer, Loxo, Rakuten Medical, Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Ono Pharmaceutical, MSD, BMS, Merck Biopharma, Eisai, Rakuten Medical; Financial Interests, Personal and Institutional, Research Grant: Bayer. R. Greil: Financial Interests, Personal, Invited Speaker: 3rd Medical Dep., Uniklinikum Salzburg; Financial Interests, Personal, Advisory Board: 3rd Medical Dep., Uniklinikum Salzburg; Financial Interests, Personal, Research Grant: 3rd Medical Dep., Uniklinikum Salzburg; Financial Interests, Personal, Advisory Role: 3rd Medical Dep., Uniklinikum Salzburg. D. Rischin: Financial Interests, Institutional, Invited Speaker: MSD, Regeneron, BMS, Replimune, GSK, Kura oncology, and Roche; Other, Personal, Advisory Board: MSD, GSK, Regeneron, and Sanofi . K.J. Harrington: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer-Ingelheim, MSD, Replimune, Arch Oncology, BMS, Codiak Biosciences, Inzen Therapeutics, Pfizer. B. Burtness: Financial Interests, Personal, Advisory Board: Merck, Vaccinex, Coherus; Financial Interests, Personal, Invited Speaker: Genentech. G. De Castro Jr.: Financial Interests, Personal and Institutional, Speaker’s Bureau: Merck Serono, Roche, MSD, Bristol Myers Squibb, AstraZeneca, GSK; Financial Interests, Personal and Institutional, Advisory Board: Merck Serono, Roche, MSD, Bristol Myers Squibb, AstraZeneca. A. Psyrri: Financial Interests, Personal, Invited Speaker: Attikon Hospital, MSD, Merck Serono,; Financial Interests, Personal and Institutional, Research Grant: Attikon, BMS, Roche, Kura Oncology; Financial Interests, Personal and Institutional, Advisory Role: Attikon, Merck Serono, BMS. I. Brana: Financial Interests, Personal, Advisory Board: Achilles Therapeutics, Bristol Myers Squibb, eTheRNA Immunotherapies, Merck Sharp & Dohme (MSD), Rakuten Pharma, PCI Biotech; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme (MSD), Roche; Financial Interests, Personal, Expert Testimony: Cancer Expert Now, Merck Serono, Boehringer Ingellheim; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Gliknik, Incyte, ISA pharmaceuticals, Debiopharm, Janssen Oncology, Kura, Merck Serono, Merck Sharp & Dohme (MSD), Nanobiotix, Novartis, Northern Biologics, Regeneron, Pfizer, Seattle Genetics, Shattuck Labs, VCN Biosciences, Roche, Immutep, MacroGenics, Sanofi, PharmaMar, Odonate Therapeutics, Bicycle Therapeutics, Dragonfly therapeutics; Non-Financial Interests, Member: SEOM, ASCO; Non-Financial Interests, Principal Investigator, Basket of baskets: Cancer Core Europe; Non-Financial Interests, Member, Head and Neck Group: EORTC. Å. Bratland: Financial Interests, Personal and Institutional, Invited Speaker: MSD, BMS, Sanofi; Financial Interests, Personal and Institutional, Advisory Board: MSD, BMS, Sanofi; Financial Interests, Personal and Institutional, Advisory Role: MSD, BMS, Sanofi. T. Fuereder: Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Roche; Pfizer; Boehringer Ingelheim; Sanofi, Merck KGaA; Amgen; Bristol Myers Squibb, Janssen; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme; Roche; Pfizer; Boehringer Ingelheim; Sanofi, Merck KGaA; Amgen; Bristol Myers Squibb, Janssen; Financial Interests, Personal and Institutional, Funding: Merck Sharp & Dohme; Roche, Merck KGaA; Amgen; Bristol Myers Squibb; Financial Interests, Personal and Institutional, Invited Speaker: Merck Sharp & Dohme; Roche, Merck KGaA; Amgen; Bristol Myers Squibb; Financial Interests, Personal and Institutional, Research Grant: Merck Sharp & Dohme; Roche, Merck KGaA; Amgen; Bristol Myers Squibb. B.G.M. Hughes: Non-Financial Interests, Personal, Advisory Board: MSD, BMS, Sanofi, Eisai; Financial Interests, Institutional, Research Grant: Amgen. R. Mesia Nin: Financial Interests, Personal, Advisory Role: Merck, MSD, BMS, Roche, Amgen, AstraZeneca, Nanobiotix, Seattle Genetics, Boehringer; Financial Interests, Personal, Principal Investigator: Merck, BMS; Financial Interests, Personal, Advisory Board: Merck, MSD, BMS; Financial Interests, Personal, Speaker’s Bureau: Merck, MSD, BMS. N. Ngamphaiboon: Financial Interests, Personal, Principal Investigator: MSD, Roche, Exelixis, RAPT Therapeutics, BeiGene, Boehringer Ingelheim Pharmaceuticals, Pfizer; Financial Interests, Personal, Project Lead: Pfizer; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Advisory Board: MSD, Novartis, Bayer, AstraZeneca, Eli Lilly; Financial Interests, Personal, Invited Speaker: Roche, MSD, Novartis, Merck. W.Z. Wan Ishak: Other, Institutional, Full or part-time Employment: University of Malaya; Financial Interests, Personal and Institutional, Invited Speaker: Merck; Financial Interests, Personal and Institutional, Writing Engagements: Merck; Financial Interests, Personal and Institutional, Speaker’s Bureau: Merck; Financial Interests, Personal and Institutional, Advisory Board: Merck; Financial Interests, Personal and Institutional, Research Grant: Merck; Financial Interests, Personal and Institutional, Funding: Merck; Financial Interests, Personal and Institutional, Sponsor/Funding: Merck; Financial Interests, Personal and Institutional, Advisory Role: Merck; Financial Interests, Personal, Invited Speaker: Amgen, Roche, AstraZeneca, Pfizer; Financial Interests, Personal, Speaker’s Bureau: Amgen, Roche; Financial Interests, Personal, Advisory Board: Amgen, Roche, AstraZeneca, Eisai; Financial Interests, Personal, Sponsor/Funding: Amgen, Roche, AstraZeneca, Eisai; Financial Interests, Personal, Advisory Role: Amgen, Roche, AstraZeneca, Eisai; Financial Interests, Personal, Writing Engagements: Roche; Financial Interests, Personal, Expert Testimony: Roche. B. Gumuscu: Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. ; Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. N. Lerman: Financial Interests, Personal, Full or part-time Employment: Merck, Sharp, and Dohme Corp. ; Financial Interests, Personal, Stocks/Shares: Merck, Sharp, and Dohme Corp. D. Soulieres: Financial Interests, Institutional, Research Grant: Merck, BMS, GSK, Adlai-Nortye; Financial Interests, Institutional, Leadership Role: Adlai-Nortye; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Advisory Board: Merck. All other authors have declared no conflicts of interest.