Abstract 3638
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
Asia, CPS ≥20 | Asia, CPS ≥1 | Asia, Total Population | Non-Asia, CPS ≥20 | Non-Asia, CPS ≥1 | Non-Asia, Total Population | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
P vs E n = 22 vs 23 | P+C vs E n = 22 vs 21 | P vs E n = 48 vs 46 | P+C vs E n = 45 vs 43 | P vs E n = 56 vs 53 | P+C vs E n = 57 vs 49 | P vs E n = 111 vs 99 | P+C vs E n = 104 vs 89 | P vs E n = 209 vs 209 | P+C vs E n = 197 vs 192 | P vs E n = 245 vs 247 | P+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 30.4 | 45.5 vs 33.3 | 16.7 vs 37.0 | 31.1 vs 37.2 | 14.3 vs 41.5 | 31.6 vs 40.8 | 23.4 vs 37.4 | 42.3 vs 39.3 | 19.6 vs 34.4 | 37.6 vs 35.4 | 17.6 vs 34.8 | 36.6 vs 35.4 |
Median DOR, mo | 5.7 vs 4.3 | 6.1 vs 4.3 | 12.6 vs 4.3 | 6.1 vs 4.2 | 12.6 vs 4.1 | 5.7 vs 4.1 | 23.4 vs 4.1 | 8.5 vs 4.1 | 20.9 vs 4.5 | 6.9 vs 4.4 | 20.9 vs 5.0 | 6.9 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.
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.
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