658MO - Pembrolizumab (pembro) vs standard-of-care (SOC) in previously treated recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): 6-year follow-up of KEYNOTE-040

Background

Pembro monotherapy is a SOC for R/M HNSCC that has progressed following platinum-containing chemo. In the phase 3 KEYNOTE-040 trial (NCT02252042), pembro had clinically meaningful prolonged OS and a favorable safety profile compared with SOC at the time (HR, 0.80; 95% CI, 0.65-0.98) in platinum-refractory R/M HNSCC. OS benefit was greater in patients (pts) with higher PD-L1 expression. Results of KEYNOTE-040 are presented after 6 years of follow-up.

Methods

Pts with incurable R/M HNSCC that progressed on or after platinum-containing chemo or ≤6 mo of prior platinum-containing multimodal therapy were randomized 1:1 to receive pembro 200 mg Q3W or investigator’s choice of methotrexate, docetaxel, or cetuximab. Primary end point was OS. Secondary end points were OS (PD-L1 CPS ≥1), ORR, DOR, PFS, and safety. Efficacy end points were evaluated in the ITT, PD-L1 TPS ≥50%, and PD-L1 CPS ≥1 populations.

Results

Of 495 pts, 15 (6.1%) and 5 (2.0%) were still being followed up in the pembro and SOC arms, respectively, as of the February 3, 2022, data cutoff date. Median follow-up was 74.8 mo (range, 68.8-85.4). Efficacy data are shown in the table. The 6-year OS rate for pembro vs SOC was 6.5% vs 2.4% for ITT, 8.9% vs 6.3% for TPS ≥50%, and 7.1% vs 2.1% for CPS ≥1 populations. Median OS for pembro vs SOC was 8.4 mo vs 7.1 mo (HR, 0.79; 95% CI, 0.66-0.94) for ITT, 11.6 mo vs 7.9 mo (HR, 0.62; 95% CI, 0.43-0.90) for TPS ≥50%, and 8.7 mo vs 7.1 mo (HR, 0.72; 95% CI, 0.59-0.89) for CPS ≥1 populations. Any-grade treatment-related AEs (TRAEs) occurred in 64.2% of pts in the pembro arm and 83.3% of pts in the SOC arm. Grade 3-5 TRAEs occurred in 13.4% of pts in the pembro arm and 36.8% in the SOC arm. Table: 658MO

“+” indicates response is ongoing

Conclusions

Pembro continued to show OS benefit compared with SOC in R/M HNSCC, regardless of PD-L1 expression, after long-term follow-up. OS hazard ratios were similar over time. These results further support the use of pembro as second-line treatment in R/M HNSCC.

Clinical trial identification

NCT02252042, release date: September 29, 2014.

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

D. Soulieres: Financial Interests, Institutional, Research Grant: Adlai-Nortye, BMS, GSK; Financial Interests, Institutional, Leadership Role: Adlai-Nortye. K.J. Harrington: Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, MSD, Replimune; Financial Interests, Institutional, Other, Consulting fees: AstraZeneca, Boehringer Ingelheim, BMS, Codiak, Idera, Inzen, ISA Pharmaceuticals, MSD, Merck-Serono, Pfizer, Replimune; Financial Interests, Institutional, Other, Honoraria: BMS, Merck-Serono, MSD. C. Le Tourneau: Financial Interests, Personal and Institutional, Advisory Board: MSD, BMS, Merck Serono, Roche, Celgene, Seattle Genetics, Nanobiotix, AstraZeneca. J.D. Silva: Financial Interests, Personal, Advisory Board: Roche, PharmaMar, BMS, Merck-Serono, MSD; Financial Interests, Personal, Principal Investigator: Roche, Boehringer Ingelheim, MSD; Financial Interests, Personal, Other, Travel expenses, including accommodation and congress fee: PharmaMar. L.F. Licitra: Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, Celgene International, Eisai, Exelixis inc, Debiopharm International SA, Hoffmann-La Roche ltd, IRX Therapeutics inc, Medpace inc, Merck–Serono, MSD, Novartis, Pfizer, Roche Spa, Buran; Financial Interests, Personal, Other, Honoraria for public speaking/teaching in medical meetings and or for expert opinion in advisory boards: AstraZeneca, Bayer, BMS, Eisai, MSD, Merck–Serono, Merck Healthcare KGaA, Boehringer Ingelheim, Hoffmann-La Roche Ltd, Novartis, Roche, Debiopharm International SA, Sobi, Incyte Biosciences Italy srl, Doxa Pharma srl, Amgen, Nanobiotics Sa, GSK; Financial Interests, Personal, Other, Honoraria for public speaking/teaching from research companies & commercial education providers: AccMed, Medical Science Fundation G. Lorenzini, Associazione Sinapsi, Think 2 IT, Aiom Servizi, Prime Oncology, WMA Congress Education, Fasi, DueCi promotion Srl, MI&T, Net Congress & Education, PRMA Consulting, Kura Oncology, Health & Life srl, Ipsen Inn; Financial Interests, Personal, Other, Travel expenses: AstraZeneca, BMS, Eisai, MSD, Merck Serono. M. Ahn: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Merck, Takeda, Daiichi Sankyo, Lilly, Roche, YUHAN, Amgen, Pfizer, Alpha Pharmaceuticals; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Amgen, Merck, Takeda, Lilly, YUHAN. A. Soria: Financial Interests, Institutional, Invited Speaker: Merck Sharp & Dohme, Bristol Myers Squibb, Novartis Pharma, Merck-Serono, Sanofi Aventis; Financial Interests, Institutional, Expert Testimony: Merck Sharpe & Dohme, Bristol Myers Squibb, Novartis Pharma, Merck-Serono, Sanofi Aventis; Financial Interests, Institutional, Advisory Board: Merck Sharp & Dohme, Bristol Myers Squibb, Novartis Pharma, Merck Serono, Sanofi Aventis; Financial Interests, Institutional, Writing Engagements: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Sanofi Aventis. J. Machiels: Financial Interests, Institutional, Advisory Board, Advisory board member or speaker with honoraria (managed by my institution): Pfizer, Roche, AstraZeneca, Bayer, Innate, Merck Serono, Boerhinger, BMS, Novartis, Janssen, Incyte, Cue Biopharma, ALX Oncology, iTEOS, eTheRNA, Nektar; Financial Interests, Personal, Other, Travel expenses: Amgen, BMS, Pfizer, MSD; Financial Interests, Personal, Other, Data safety monitoring board with honoraria: Psioxus; Financial Interests, Institutional, Research Grant: Pfizer, Roche, AstraZeneca, Bayer, Innate, Merck Serono, Boerhinger, BMS, Novartis, Janssen, Incyte, Cue Biopharma, ALX Oncology, iTEOS, eTheRNA, Nektar, Amgen, BMS, Psioxus; Non-Financial Interests, Personal, Advisory Role, Uncompensated: MSD. N. Mach: Financial Interests, Personal, Stocks/Shares: MaxiVAX. R. Mehra: Non-Financial Interests, Personal, Advisory Board: AstraZeneca; Non-Financial Interests, Personal, Advisory Role: AstraZeneca; Other, Personal, Other: AstraZeneca; Financial Interests, Personal, Advisory Board: Coherus; Financial Interests, Personal, Advisory Role: Coherus; Other, Institutional, Research Grant: Merck; Other, Institutional, Principal Investigator: Merck. B. Burtness: Financial Interests, Personal, Advisory Board: Merck, Vaccinex, Coherus; Financial Interests, Personal, Invited Speaker: Genentech. J. Lin: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.. N. Lerman: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. B. Gumuscu: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. E.E..W. Cohen: Non-Financial Interests, Personal, Advisory Role: Axelia, Cel Sci, Eisai, Hoopika, ImmunoSensor, Istari, Janssen, Kahr Medical, Mana Therapeutics, Merck, Mirati, MSD, Nectin Tx, Pangea Therapeutics, Roche; Non-Financial Interests, Personal, Member of the Board of Directors: Therapeutics, NCCN; Financial Interests, Personal, Stocks/Shares: Kinnate Biopharma, Primmune Therapeutics; Non-Financial Interests, Personal, Leadership Role: Ayala, Kura, Kinnate Biopharma.