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Poster Display session 3

3638 - Phase 3 KEYNOTE-048 Study of First-Line (1L) Pembrolizumab (P) for Recurrent/Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC): Asia vs Non-Asia Subgroup (subgrp) Analysis


30 Sep 2019


Poster Display session 3


Tumour Site

Head and Neck Cancers


Makoto Tahara


Annals of Oncology (2019) 30 (suppl_5): v449-v474. 10.1093/annonc/mdz252


M. Tahara1, R. Hong2, W.Z. Wan Ishak3, C. Yen4, V. Sriuranpong5, S. Takahashi6, V. Srimuninnimit7, S. Yeh8, N. Oridate9, M. Yang10, K. Tanaka11, N. Nohata12, Y. Koh12, A. Roy13, B. Gumuscu13, R.F. Swaby13, N. Ngamphaiboon14

Author affiliations

  • 1 Head And Neck Medical Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 2 Oncology, National Taiwan University Hospital, Taipei/TW
  • 3 Clinical Oncology, University of Malaya, Kuala Lumpur/MY
  • 4 Medical Oncology, National Cheng Kung University, 704 - Tainan/TW
  • 5 Medical Oncology, Chulalongkorn University, Bangkok/TH
  • 6 Medical Oncology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo/JP
  • 7 Medical Oncology, Medicine, Siriraj Hospital, Mahidol University, Bangkok/TH
  • 8 Medical Oncology, China Medical University Hospital, Taichung/CN
  • 9 Otolaryngology-head And Neck, Yokohama City University Graduate School of Medicine, Yokohama/JP
  • 10 Medical Oncology, Taipei Veterans General Hospital, Taipei/TW
  • 11 Medical Oncology, Kindai University Faculty of Medicine, 589-8511 - Osaka/JP
  • 12 Medical Oncology, MSD K.K, Tokyo/JP
  • 13 Medical Oncology, Merck & Co., Inc., 07033 - Kenilworth/US
  • 14 Medicine, Ramathibodi Hospital, Mahidol University, Bangkok/TH


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Abstract 3638


KEYNOTE-048 (NCT02358031) is a randomized, open-label, phase 3 trial of P or P + chemotherapy (C) vs EXTREME (E) as 1L therapy for R/M HNSCC. At 2nd interim analysis, overall survival (OS) was significantly longer with P than E in patients (pts) with PD-L1 combined positive score (CPS) ≥20 (P = 0.0007) and CPS ≥1 (P = 0.0086) and was noninferior in the total population (pop). P+C significantly improved OS vs E in the total pop (P = 0.0034). Safety was favorable or similar to that of E.


Pts with R/M HNSCC not curable by local therapy and with no prior systemic therapy were randomized (1:1:1) to P 200 mg Q3W, P+C (cisplatin 100 mg/m2 or carboplatin AUC 5 Q3W + 5-FU 1000 mg/m2/day for 4 days Q3W), or E (cetuximab 400 mg/m2 loading dose with 250 mg/m2 subsequent infusion QW + C) until progressive disease, unacceptable toxicity, 6 cycles of C, or 24 months of P. Primary end points were progression-free survival and OS. Data cutoff date was June 13, 2018.


Efficacy is reported in the table. Gr 3-5 drug-related AE rates with P vs E were 28.6% vs 76.9% in the Asia subgrp and 13.9% vs 67.2% in the non-Asia subgrp; rates with P+C vs E were 71.9% vs 76.9% in the Asia subgrp and 70.8% vs 67.2% in the non-Asia subgrp.Table: 1136P

Asia, CPS ≥20Asia, CPS ≥1Asia, Total PopulationNon-Asia, CPS ≥20Non-Asia, CPS ≥1Non-Asia, Total Population
P vs E n = 22 vs 23P+C vs E n = 22 vs 21P vs E n = 48 vs 46P+C vs E n = 45 vs 43P vs E n = 56 vs 53P+C vs E n = 57 vs 49P vs E n = 111 vs 99P+C vs E n = 104 vs 89P vs E n = 209 vs 209P+C vs E n = 197 vs 192P vs E n = 245 vs 247P+C vs E n = 224 vs 229
OS: HR (95% CI )0.39 (0.19-0.80)0.80 (0.41-1.58)0.80 (0.51-1.27)1.13 (0.71-1.79)0.74 (0.48-1.13)1.03 (0.68-1.58)0.75 (0.54-1.04)0.68 (0.48-0.96)0.76 (0.61-0.95)0.65 (0.51-0.82)0.87 (0.71-1.06)0.71 (0.57-0.88)
PFS: HR (95% CI)1.16 (0.63-2.11)1.07 (0.58-1.99)1.25 (0.82-1.91)1.14 (0.74-1.76)1.39 (0.94-2.05)1.12 (0.75-1.66)0.95 (0.70-1.28)0.65 (0.47-0.89)1.10 (0.89-1.35)0.74 (0.60-0.92)1.27 (1.05-1.54)0.82 (0.67-1.00)
ORR, %22.7 vs 30.445.5 vs 33.316.7 vs 37.031.1 vs 37.214.3 vs 41.531.6 vs 40.823.4 vs 37.442.3 vs 39.319.6 vs 34.437.6 vs 35.417.6 vs 34.836.6 vs 35.4
Median DOR, mo5.7 vs 4.36.1 vs 4.312.6 vs 4.36.1 vs 4.212.6 vs 4.15.7 vs 4.123.4 vs 4.18.5 vs 4.120.9 vs 4.56.9 vs 4.420.9 vs 5.06.9 vs 5.0

C, chemotherapy; CI, confidence interval; CPS, combined positive score; DOR, duration of response; E, EXTREME; HR, hazard ratio; mo, months; ORR, objective response rate; OS, overall survival; P, pembrolizumab; PFS, progression-free survival. HRs are from product-limit (Kaplan-Meier) method for censored data; 95% CIs are based on Cox regression model with Efron’s method of tie handling with treatment as a covariate.


P vs E showed favorable OS in Asia and non-Asia subgrps, regardless of PD-L1 status; responses were durable, particularly among all non-Asia subgrps; safety was favorable. P+C vs E showed favorable OS in pts with CPS ≥20 in Asia and non-Asia subgrps regardless of PD-L1 status, durable responses, and similar safety.

Clinical trial identification


Editorial acknowledgement

Doyel Mitra, 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.


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


M. Tahara: Honoraria (self): Merck Serono, Bristol-Myers Squibb, Eisai, Ono Pharmaceutical, MSD, AstraZeneca; Advisory / Consultancy: Merck Serono, Bristol-Myers Squibb, Ono Pharmaceutical, MSD, Pfizer, Rakuten Medical, Celgene, Amgen; Research grant / Funding (institution): Bristol-Myers Squibb, Ono Pharmaceutical, MSD, Pfizer, Rakuten Medical, Novartis, Loxo, AstraZeneca, Rakuten Medical. R. Hong: Research grant / Funding (institution): MSD. W.Z. Wan Ishak: Honoraria (self): Eli Lilly Malaysia, Roche Malaysia, Pfizer Malaysia MSD Ltd, Eisai Korea, Eisai Malaysia, Mundipharma, Merck Serono, Roche Myanmar; Advisory / Consultancy: Boehringer Ingelheim, Merck Serono, Roche, Eli Lilly, Amgen; Speaker Bureau / Expert testimony: Eli Lilly; Research grant / Funding (self): Amgen Inc, MSD, Roche, Genentech, AstraZeneca; Travel / Accommodation / Expenses: Eisai, Eli Lilly, AstraZeneca, MSD Inc, Roche, Merck Serono, Mundipharma, Novartis, Pfizer, Amgen, Menarini. S. Takahashi: Honoraria (self): Novartis, MDS, Eisai, Taiho, Chugai, Daiichi-Sankyo, Bayer, AstraZeneca; Research grant / Funding (self): MSD, Eisai, Taiho, Chugai, Daiichi-Sankyo, Bayer, AstraZeneca, Quintiles. K. Tanaka: Honoraria (self): AstraZeneca, ONO Pharmaceutical, MSD, Eisai, Merck Serono, Bristol-Myers Squibb. N. Nohata: Shareholder / Stockholder / Stock options: Merck & Co., Inc.; Full / Part-time employment: MSD K.K. A. Roy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck. B. Gumuscu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck. R.F. Swaby: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck. N. Ngamphaiboon: Honoraria (self): Roche, AstraZeneca, Eisai, Amgen, MSD, Novartis; Advisory / Consultancy: MSD, Amgen, Novartis, Boehringer Ingelheim, AstraZeneca; Speaker Bureau / Expert testimony: Roche, AstraZeneca, Eisai, Amgen, MSD, Novartis; Travel / Accommodation / Expenses: Roche, MSD, Amgen, Novartis, Merck, Eisai, Taiho; Research grant / Funding (institution): MSD, Pfizer, Roche, AstraZeneca. All other authors have declared no conflicts of interest.

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