915MO - Long-term outcomes from KEYNOTE-048: Pembrolizumab (pembro) alone or with chemotherapy (pembro+C) vs EXTREME (E) as first-line (1L) therapy for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC)

Background

In the phase III KEYNOTE-048 study, pembro significantly prolonged OS vs E in patients (pts) with PD-L1 combined positive score (CPS) ≥20 and CPS ≥1 and had noninferior OS in the total population (pop). Pembro+C significantly prolonged OS vs E in the PD-L1 CPS ≥20, CPS ≥1, and total pops. Safety was favorable for pembro vs E and comparable for pembro+C vs E. Results with 4y follow-up are shown.

Methods

Pts with locally incurable R/M HNSCC were randomized to 1L pembro 200 mg Q3W for 24 mo, pembro+C, or E. Pts in the pembro or pembro+C arms who stopped pembro with stable disease or better and then had PD could receive a second course of pembro if eligible. Follow-up was defined as time from randomization to database cutoff. Efficacy was analyzed in the ITT pop; safety was analyzed in all randomized pts who received ≥1 dose of study drug.

Results

Median study follow-up (March 25, 2020) was 46.2 mo for pembro vs E and 45.6 mo for pembro+C vs E. Pembro and pembro+C improved OS vs E in the CPS ≥20, CPS ≥1, and total pops (Table). Pembro 48-mo OS was 21.6%, 16.7%, and 15.4% in the CPS ≥20, CPS ≥1, and total pops, respectively, vs 8.0%, 5.9%, and 6.6% for E. Pembro+C 48-mo OS was 28.6%, 21.8%, and 19.4% in the CPS ≥20, CPS ≥1, and total pops, respectively, vs 6.6%, 4.1%, and 4.5% for E. OS, PFS, ORR, and DOR data are shown in the table. Treatment-related grade 3-5 AEs: 17.0% for pembro, 71.7% for pembro+C, and 69.3% for E. In all, 11 pts (pembro, 6; pembro+C, 5) received a secondcourse of pembro; ORR for second course was 36.4% (CR, 1; PR, 3).

Conclusions

Long-term follow-up confirmed the statistically significant improvement in OS established at the protocol-specified interim and final analyses for pembro vs E in pts with PD-L1 CPS ≥20 and CPS ≥1 and for pembro+C vs E in pts with PD-L1 CPS ≥20 and CPS ≥1, and total pop. Safety was favorable for pembro vs E and comparable for pembro+C vs E Table: 915MO

*Nominal values; not adjusted for multiplicity. P, pembrolizumab.

Clinical trial identification

NCT02358031; February 6, 2015.

Editorial acknowledgement

Medical writing and editorial assistance was provided by Doyel Mitra, PhD, CMPP, and Jo Bairzin, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was 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

R. Greil: Advisory/Consultancy: Celgene, Novartis, Roche, Bristol-Myers Squibb, Takeda, AbbVie, AstraZeneca, Janssen, MSD, Merck, Gilead Sciences, Daiichi Sankyo; Travel/Accommodation/Expenses: Rocher, Amgen, Janssen-Cilag, AstraZeneca, Novartis, MSD, Celgene, Gilead Sciences, Bristol-Myers Squibb; Honoraria (self): Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, Bristol-Myers Squibb, MSD, Sandoz, AbbVie, Gilead Sciences, Daiichi Sankyo; Research grant/Funding (institution): Celgene, Merck, Takeda, AstraZeneca, Novartis, Amgen, Bristol-Myers Squibb, MSD, Sandoz, Gilead Sciences, Roche. D. Rischin: Travel/Accommodation/Expenses: Merck; Research grant/Funding (self): Genentech/Roche, Merck, Regeneron, Bristol-Myers Squibb, GlaxoSmithKline, Sanofi. K.J. Harrington: Honoraria (institution), Advisory/Consultancy: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Serono, MSD, Oncolys, Pfizer, Replimune; Research grant/Funding (institution): AstraZeneca, Boehringer Ingelheim, MSD, Replimune. D. Soulières: Advisory/Consultancy: Merck, Pfizer, Ipsen; Honoraria (self): Merck, Novartis, Pfizer, AstraZeneca, Ipsen, Bristol-Myers Squibb, Eisai, Adlai-Nortye; Research grant/Funding (institution): Novartis, Pfizer, Merck, Roche/Genentech, Bristol-Myers Squibb, Lilly. M. Tahara: Advisory/Consultancy: Ono Pharmaceutical, MSD, Pfizer, Bristol-Myers Squibb, Celgene, Amgen, Rakuten Medical, Bayer; Honoraria (self): Merck Serono, Bristol-Myers Squibb, Eisai, Ono Pharmaceutical MSD, AstraZeneca; Research grant/Funding (institution): Merck Sharp & Dohme, AstraZeneca, Ono Pharmaceutical, Novartis, Pfizer, Bristol-Myers Squibb, Loxo, Rakuten Medical, Bayer. G. de Castro: Advisory/Consultancy: Teva, Boehringer Ingelheim, Pfizer, Bayer, Roche, Merck Sharp & Dohme, Bristol-Myers Squibb, AstraZeneca, Yuhan; Speaker Bureau/Expert testimony: AstraZeneca, Bayer, Novartis, Roche, Merck Serono, Bristol-Myers Squibb, Merck Sharp & Dohme, Boehringer Ingelheim, Pfizer; Travel/Accommodation/Expenses: Merck Sharp & Dohme, Novartis, Pfizer, Roche, AstraZeneca, Boehringer Ingelheim, Bayer, Bristol-Myers Squibb; Honoraria (self): AstraZeneca, Pfizer, Merck Sharp & Dohme, Bristol-Myers Squibb, Novartis, Roche, Boehringer Ingelheim. A. Psyrri: Advisory/Consultancy: AstraZeneca, MSD Oncology, Pfizer, Bristol-Myers Squibb, Amgen, Rakuten; Travel/Accommodation/Expenses: Roche, MSD Oncology, Ipsen, Bristol-Myers Squibb, Ipsen; Honoraria (self): Merck Serono, Roche, Bristol-Myers Squibb, MSD Oncology, Genesis Pharmaceuticals, Bayer, Rakuten, AstraZeneca, Pfizer; Research grant/Funding (self): Kura, Bristol-Myers Squibb, Roche, Amgen, Boehringer Ingelheim, Pfizer, Demo Pharmaceutical, Pharmaten; Non-remunerated activity/ies: AstraZeneca. N. Baste: Advisory/Consultancy: Bristol-Myers Squibb, Merck Serono, Nanobiotix; Travel/Accommodation/Expenses: Bristol-Myers Squibb, Merck Serono, Nanobiotix, AstraZeneca, GlaxoSmithKline, MSD. P. Neupane: Advisory/Consultancy: Pfizer/EMD Serono; Research grant/Funding (self): Merck Sharp & Dohme, Bristol-Myers Squibb. T. Fuereder: Honoraria (self): MSD, Merck Darmstadt, Roche, Bristol-Myers Squibb, Accord Healthcare, Sanofi, Boehringer Ingelheim; Advisory/Consultancy: MSD, Merck Darmstadt, Amgen, Pfizer, Sanofi; Research grant/Funding (institution): MSD, Merck Darmstadt, Bristol-Myers Squibb; Travel/Accommodation/Expenses: Roche, MSD, Bristol-Myers Squibb. B.G.M. Hughes: Advisory/Consultancy: MSD Oncology, Bristol-Myers Squibb, Roche, Pfizer, Boehringer Ingelheim, AstraZeneca, Eisai; Research grant/Funding (institution): Amgen. R. Mesia, Sr.: Advisory/Consultancy: Bristol-Myers Squibb, MSD, Merck KGaA, Roche, AstraZeneca, Nanobiotix; Speaker Bureau/Expert testimony: Bristol-Myers Squibb, Merck KGaA; Travel/Accommodation/Expenses: Merck KGaA, Bristol-Myers Squibb, Roche. N. Ngamphaiboon: Advisory/Consultancy: Roche, MSD, Amgen, Novartis, Boehringer Ingelheim, Taiho Pharmaceutical; Speaker Bureau/Expert testimony: Roche, AstraZeneca, Eisai, Amgen, MSD, Novartis; Travel/Accommodation/Expenses: Roche, MSD, Amgen, Novartis, Merck, Eisai, Taiho Pharmaceutical; Honoraria (self): Roche, AstraZeneca, Eisai, Amgen, MSD, Novartis; Research grant/Funding (self): MSD, Pfizer, Roche, AstraZeneca. T. Rordorf: Advisory/Consultancy: MSD, Bristol-Myers Squibb. W.Z. Wan Ishak: Honoraria (self): MSD Ltd, Eisai Korea, Eisai Malaysia, Mundipharma, Merck Serono, Roche Myanmar, Eli Lilly Malaysia, Roche Malaysia, Pfizer Malaysia, Amgen Malaysia; Advisory/Consultancy: Eli Lilly Malaysia, Merck Serono Malaysia, Roche Malaysia, Mundi Pharma Malaysia, Boehringer Ingelheim Malaysia; Speaker Bureau/Expert testimony: Roche Malaysia, Eli Lilly Malaysia, Boehringer Ingelheim Malaysia; Research grant/Funding (institution): Roche, Amgen, Merck; Travel/Accommodation/Expenses: MSD Ltd, Eisai Korea, Disai Malaysia, Mundipharma, Merck Serono, Roche Myanmar, Eli Lilly Malaysia, Roche Malaysia, Pfizer Malaysia, Amgen Malaysia, Amgen Malaysia, Eli Lilly Malaysia, Merck Serono Malaysia, Mundi Pharma Malaysia, Boehringer Ingelheim Mal. J. Lin: Full/Part-time employment: Merck. R.F. Swaby, B. Gumuscu: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck. B. Burtness: Advisory/Consultancy: Merck, Debiopharm Group, AstraZeneca, Bristol-Myers Squibb, Alligator Bioscience, Aduro Biotech, GlaxoSmithKline, Celgene, CUE Biopharma, Maverick therapeutics, Rakuten, Nanobiotix, Macrogenics, ALX Oncology; Travel/Accommodation/Expenses: Merck, Debiopharm Group, Boehringer Ingelheim; Honoraria (self): AstraZeneca; Research grant/Funding (institution): Merck, Aduro Biotech, Formation Biologics, Bristol-Myers Squibb, Exelixis. All other authors have declared no conflicts of interest.