106P - Treatment Sequencing in PD-L1-Positive Recurrent/Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC): Exploratory Analysis of the Phase 3 KEYNOTE-048 Study

Background

Pembrolizumab (pembro) and pembro + platinum + 5-FU (pembro + chemo) are standard-of-care options alongside cetuximab-based regimens such as EXTREME (cetuximab + platinum + 5-FU) for R/M HNSCC, depending on PD-L1 expression and clinical circumstances, but optimal sequencing has not been defined. We present OS in pts with PD-L1+ R/M HNSCC who received first-line (1L) pembro or pembro + chemo followed by cetuximab-based therapy, or EXTREME followed by immunotherapy (IO), in KEYNOTE-048 (NCT02358031).

Methods

Pts with locally incurable R/M HNSCC were randomly assigned 1:1:1 to 1L pembro, pembro + chemo, or EXTREME. This post hoc exploratory analysis included pts with PD-L1 CPS ≥1 who received second-line (2L) cetuximab-based therapy (cetux) after pembro or pembro + chemo, or 2L IO after EXTREME.

Results

Of 882 pts, 170 with PD-L1 CPS ≥1 who received 2L cetux or IO were included (1L pembro, n = 63; pembro + chemo, n = 37; EXTREME, n = 70). Median follow-up was 69.3 mo (range, 61.2-81.2). Median OS (95% CI) was 15.7 mo (12.3-22.6) for pts who received pembro followed by cetux vs 16.5 mo (13.5-19.8) for EXTREME followed by IO (HR, 1.0; 95% CI, 0.7-1.5); 24-mo OS was 32% vs 31%. Median OS (95% CI) was 22.1 mo (14.0-24.7) for pts who received pembro + chemo followed by cetux vs 16.5 mo (11.5-19.8) for EXTREME followed by IO (HR, 0.7; 95% CI, 0.4-1.0); 24-mo OS was 39% vs 30%. Median OS (95% CI) was 16.6 mo (13.8-23.2) for all pts who received pembro or pembro + chemo (n = 100) followed by cetux vs 16.5 mo (13.5-19.8) for EXTREME followed by IO (HR, 0.9; 95% CI, 0.6-1.2); 24-mo OS was 34% vs 31%. Of pts receiving pembro or pembro + chemo, 13 received subsequent cetux monotherapy and 87 received cetux + chemo.

Conclusions

In this post hoc exploratory analysis of KEYNOTE-048, OS was longer for pts who received pembro + chemo followed by cetux vs EXTREME followed by IO and was similar for pts who received pembro followed by cetux vs EXTREME followed by IO. Clinical factors may have contributed to different use of 2L therapies by treatment arm. These findings, in addition to the primary analysis of KEYNOTE-048, support 1L pembro and pembro + chemo in PD-L1–positive R/M HNSCC.

Clinical trial identification

NCT02358031.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by 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

R. Greil: Financial Interests, Personal, Advisory Board: Celgene, Novartis, Roche, BMS, Takeda, AbbVie, AstraZeneca, Janssen, MSD, Merck, Gilead, Daiichi Sankyo, Sanofi; Financial Interests, Institutional, Stocks/Shares: Novo Nordisk, Lilly; Financial Interests, Personal and Institutional, Funding: Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, BMS, MSD, Sandoz, AbbVie, Gilead, Daiichi Sankyo; Non-Financial Interests, Personal, Other, Travel, Accomodation, Expenses, Consulting, Adv Role: Roche, Amgen, Janssen, AstraZeneca Novartis, MSD, Celgene, Gilead, BMS, AbbVie, Daiichi Sankyo, Sanofi; Other, Personal, Other, Travel, Accomodation, Expenses, Consulting, Adv Role, Honoraria: Roche, Amgen, Janssen, AstraZeneca, Novartis, MSD, Celgene, Gilead, BMS, AbbVie, Daiichi Sankyo, Sanofi. B. Burtness: Financial Interests, Personal, Advisory Board: Merck, Vaccinex, Coherus; Financial Interests, Personal, Invited Speaker: Genentech. S. Laban: Financial Interests, Institutional, Advisory Board: Merck Sharp & Dohme, Bristol Myers Squibb, Sanofi Genzyme; Financial Interests, Institutional, Invited Speaker: Merck Sharp & Dohme, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Institutional, Other, patent for an oropharyngeal cancer multi-peptide vaccine (pending): filed patent (patent pending); Non-Financial Interests, Personal, Principal Investigator: Immutep, Merck Sharp & Dohme, Bristol Myers Squibb, ISA-Pharmaceuticals. I. Braña: Financial Interests, Personal, Advisory Board: Achilles Therapeutics, Bristol Myers Squibb, Cancer Expert Now, eTheRNA Immunotherapies, Merck Serono, Merck Sharp & Dohme (MSD), Rakuten Pharma, Boehringer Ingelheim, PCI Biotech, Guidepoint; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme (MSD), Roche; Financial Interests, Institutional, Local PI: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, GSK, Gliknik, Incyte, ISA Pharmaceuticals, Janssen Oncology, Kura, Merck Serono, Novartis, Debiopharm, Merck Sharp & Dohme (MSD), Nanobiotix, Northern Biologics, Regeneron, Pfizer, Seattle Genetics, Shattuck Labs, VCN Biosciences, Roche, Immutep, MacroGenics, Sanofi, PharmaMar, Odonate Therapeutics, Bicycle Therapeutics, Dragonfly therapeutics, Gilead; Non-Financial Interests, Personal, Principal Investigator, Basket of baskets: Cancer Core Europe; Non-Financial Interests, Personal, Member, Head and Neck Group: EORTC; Non-Financial Interests, Personal, Member: SEOM, ASCO. R. Mesia Nin: Financial Interests, Personal, Advisory Board: Merck, MSD, Bayer, Seattle Genetics, Nanobiotix, Boehringer, Segean; Financial Interests, Personal, Invited Speaker: Merck, MSD, BMS; Non-Financial Interests, Personal, Principal Investigator, Clinical Trial PI: BMS; Non-Financial Interests, Personal, Principal Investigator, Observational trial PI: Merck. T. Fuereder: Financial Interests, Personal, Advisory Board: MSD, Pfizer, Boehringer Ingelheim, Sanofi, Merck KGaA, Amgen, Bristol Myers Squibb, Janssen; Financial Interests, Personal, Invited Speaker: MSD, Pfizer, Boehringer Ingelheim, Sanofi, Merck KGaA, Amgen, Bristol Myers Squibb, Janssen; Financial Interests, Personal, Research Funding: Merck Sharp & Dohme; Financial Interests, Personal, Research Grant: Merck Sharp & Dohme; Financial Interests, Personal and Institutional, Principal Investigator: Merck Sharp & Dohme, Roche, Merck KGaA, Amgen, Bristol Myers Squibb; Financial Interests, Personal and Institutional, Research Funding: Roche, Merck KGaA, Amgen, Bristol Myers Squibb; Financial Interests, Personal and Institutional, Research Grant: Roche, Merck KGaA, Amgen, Bristol Myers Squibb. î Bratland: Financial Interests, Personal and Institutional, Invited Speaker: MSD, BMS, Sanofi; Financial Interests, Personal and Institutional, Advisory Board: MSD, Sanofi; Financial Interests, Personal and Institutional, Principal Investigator: MSD, BMS; Financial Interests, Personal and Institutional, Advisory Role: Sanofi. L.F.L. Licitra: Financial Interests, Personal, Advisory Board, for expert opinion in advisory boards: AstraZeneca, Bayer, BMS, Eisai, MSD, Boehringer Ingelheim, Hoffmann-La Roche Ltd, Novartis, Roche, Debiopharm International SA, Sobi, Incyte Biosciences Italy srl, Doxa Pharma srl, Amgen, Nanobiotics, GSK; Financial Interests, Institutional, Research Grant, Funds received by my institution for clinical studies and research activities in which I am involved: AstraZeneca, BMS, Boehringer Ingelheim, Celgene International, Eisai, Exelixis, Debiopharm International SA, Hoffmann-La roche ltd, IRX Therapeutics, Medpace, Merck Serono, Merck Healthcare KGaA, MSD, Novartis, Pfizer, Roche, Adlai Nortye. A. Psyrri: Financial Interests, Personal, Invited Speaker: MSD, Merck Serono; Financial Interests, Personal, Advisory Board: Pfizer, Sanofi, MSD, AstraZeneca, BMS, Leo, Rakuten, eTheRNA immunotherapies, Merck Serono; Financial Interests, Personal and Institutional, Local PI: AstraZeneca, Pfizer, GSK, Genesis, MSD, Incyte, Amgen, Debiopharm, Janssen, Lilly, Regeneron, Sanofi, BI, Roche, Peregrine, Oncolytics Biotech; Financial Interests, Personal, Coordinating PI: AstraZeneca; Financial Interests, Personal and Institutional, Steering Committee Member: Iovance, Pfizer, Roche; Financial Interests, Institutional, Steering Committee Member: Kura Oncology; Financial Interests, Personal, Steering Committee Member: Kura Oncology; Financial Interests, Personal and Institutional, Funding: Kura Oncology, BMS, Roche, DEMO, Amgen, BI, Genesis, BMS, Pfizer, Oncolytics Biotech; Financial Interests, Institutional, Funding: Merck Serono, Pfizer; Financial Interests, Personal, Other, Educational activity: Medscape, PrimeOncology; Financial Interests, Institutional, Local PI: Novartis, Replimmune; Non-Financial Interests, Personal, Project Lead, Medical Education with honoraria: Medscape. B. Hughes: Non-Financial Interests, Personal, Advisory Board: MSD, BMS, Sanofi, Eisai; Financial Interests, Institutional, Research Grant: Amgen. M. Tahara: Financial Interests, Personal, Advisory Board: Merck Biopharma, Ono Pharma, Bristol Myers Squibb, MSD, Pfizer, Bayer, Lilly, Rakuten Medical, Boehringer Ingelheim, AstraZeneca; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Institutional, Local PI: MSD, AstraZeneca, Ono Pharma, Novartis, Pfizer, Bristol Myers Squibb, Loxo, GSK, Lilly, Rakuten Medical, Bayer, Merckbiophama; Financial Interests, Institutional, Research Grant: Bayer. J. Lin, B. Gumuscu, N. Lerman: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. K.J. Harrington: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Merck, MSD, Pfizer, Replimune, Oncolys, Vyriad, Idera; Financial Interests, Institutional, Other, Honoraria for lectures: Amgen, AstraZeneca, BMS, Boehringer Ingelheim; Financial Interests, Institutional, Advisory Board, Advisory board for CD47 assets: Arch Oncology; Financial Interests, Institutional, Advisory Board, Development of DDR assets: ARTIOS; Financial Interests, Institutional, Advisory Board, Development of exosomal STING agonist: Codiak; Financial Interests, Institutional, Advisory Board, Development of oncolytic adenovirus: PsiVac; Financial Interests, Institutional, Funding, Research: AstraZeneca, Boehringer Ingelheim, MSD; Financial Interests, Institutional, Funding, Development of oncolytic HSV platform: Replimune; Non-Financial Interests, Personal, Leadership Role, Chair of Steering Committee: ART NET; Non-Financial Interests, Personal, Other, Member of Global Steering Committee: MR - Linac. All other authors have declared no conflicts of interest.