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

Background

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.

Methods

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.

Results

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

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.

Conclusions

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

NCT02358031.

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.

Funding

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

Disclosure

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.