LBA35 - Avelumab-cetuximab-radiotherapy versus standards of care in patients with locally advanced squamous cell carcinoma of head and neck (LA-SCCHN): Randomized phase III GORTEC-REACH trial
- Jean Bourhis (Lausanne, Switzerland)
Abstract
Background
Based on a potential synergistic effect of anti–PD-L1 avelumab plus cetuximab and radiotherapy (RT), this combination was tested in a randomized phase III trial against 2 standards of care (SOC) in LA-SCCHN.
Methods
The trial comprised 2 cohorts of patients (pts) fit for cisplatin (3 cycles of 100 mg/m2, Q3W) or unfit for cisplatin. The SOC was IMRT 70 Gy / 6.5 weeks with cisplatin in fit pts and with cetuximab in unfit pts (
Results
Between 2017 and 2020, 707 pts were randomized.
Conclusions
In cisplatin-Unfit pts, a favorable effect of adding avelumab to cetuximab was seen on PFS, local-regional control, distant metastases, but the primary endpoint on PFS was not met. In cisplatin-Fit pts, the futility boundary for efficacy was crossed, favoring SOC cisplatin.
Clinical trial identification
NCT02999087.
Legal entity responsible for the study
GORTEC.
Funding
GORTEC with a funding from MERCK Serono. This research was financially supported by Merck Serono S.A.S., Lyon, France, an affiliate of Merck KGaA, as part of an alliance between Merck (CrossRef Funder ID: 10.13039/100009945) and Pfizer.
Disclosure
All authors have declared no conflicts of interest.
LBA36 - Nivolumab (N) + ipilimumab (I) vs EXTREME as first-line (1L) treatment (tx) for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): Final results of CheckMate 651
- Athanassios Argiris (Marousi, Greece)
Abstract
Background
Despite recent tx advances in R/M SCCHN, durable survival benefit remains an elusive goal. CheckMate 651 (NCT02741570), a phase 3 randomized trial, evaluated N+I vs EXTREME regimen as 1L tx for platinum-eligible R/M SCCHN.
Methods
Pts with R/M SCCHN, no prior systemic therapy in R/M setting, and ECOG PS 0–1 were randomized 1:1 to N (3 mg/kg Q2W) + I (1 mg/kg Q6W; n = 472), or EXTREME (n = 475), stratified by tumor PD-L1 level, p16 expression, and prior chemotherapy. Pts were treated with N+I or EXTREME (cetuximab + cisplatin/carboplatin + fluorouracil ≤6 cycles, then cetuximab maintenance) until progression/unacceptable toxicity, or 2 y for N+I. Primary endpoints were overall survival (OS) in all randomized and PD-L1 combined positive score (CPS) ≥20 populations. OS in CPS ≥1 was a key secondary endpoint. Progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and safety were also assessed.
Results
947 pts were randomized; baseline characteristics were balanced across arms. At final analysis (minimum follow-up: 27.3 mo), there was no statistically significant improvement in OS with N+I vs EXTREME in all randomized (HR 0.95 [97.9% CI: 0.80–1.13]
Conclusions
N+I did not show statistically significant OS improvement vs EXTREME in pts with R/M SCCHN; however, there was evidence of clinical activity in pts with CPS ≥20 and CPS ≥1 as shown by prolonged OS (median and 2 y rates) and durable responses. Notably, OS in the control arm was better than historical data. N+I had a favorable safety profile vs EXTREME, with no new safety signals observed.
All randomized CPS ≥20 CPS ≥1 N+I EXTREME N+I EXTREME N+I EXTREME n 472 475 185 178 355 372 Median OS, mo 95% CI 13.9 12.1–15.8 13.5 12.6–15.2 17.6 13.8–22.0 14.6 12.3–16.0 15.7 13.7–18.8 13.2 11.1–14.6 HR CI 0.95 97.9% CI: 0.80–1.13 0.78 97.5% CI: 0.59–1.03 0.82 95% CI: 0.69–0.97 0.4951 0.0469 - 2-y OS, % 31 28 41 33 34 28 Median PFS, mo 3.3 6.7 5.4 7.0 4.2 2.9-5.4 6.1 5.6-7.0 HR 95% CI 1.41 1.21−1.65 1.02 0.78–1.33 1.23 1.03−1.47 2-y PFS, % 15 13 26 16 18 13 ORR, n (%) 95% CI 114 (24) 20−28 175 (37) 32−41 63 (34) 27−41 64 (36) 29−44 98 (28) 23-33 133 (36) 31-41 Median DOR, mo 95% CI 16.6 5.9 32.6 7.0 18.3 10.9-32.6 6.0 5.6-7.6 18 mo DOR, % 48 20 62 29 52 22
Clinical trial identification
NCT02741570.
Editorial acknowledgement
Writing and editorial assistance was provided by Brooke Middlebrook, CMPP, of Evidence Scientific Solutions, funded by Bristol Myers Squibb.
Legal entity responsible for the study
Bristol Myers Squibb and Ono Pharmaceutical Company Ltd.
Funding
Bristol Myers Squibb (all study sites) and Ono Pharmaceuticals (study sites in Japan, Korea and Taiwan).
Disclosure
A. Argiris: Financial Interests, Personal, Other, Review Committee: AstraZeneca; Financial Interests, Personal, Funding: BMS; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Other, Review Committee: Debiopharm; Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Advisory Board: Rakuten Medical, Inc.; Financial Interests, Personal, Funding: Rakuten Medical, Inc. K. Harrington: Financial Interests, Institutional, Advisory Board: Arch Oncology; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Advisory Board: Boehringer-Ingelheim; Financial Interests, Institutional, Research Grant: Boehringer-Ingelheim; Financial Interests, Institutional, Advisory Board: Codiak; Financial Interests, Institutional, Advisory Board: Inzen; Financial Interests, Institutional, Advisory Board: Merck-Serono; Financial Interests, Institutional, Invited Speaker: Merck-Serono; Financial Interests, Personal and Institutional, Advisory Board: MSD; Financial Interests, Personal and Institutional, Invited Speaker: MSD; Financial Interests, Personal and Institutional, Research Grant: MSD; Financial Interests, Institutional, Advisory Board: Oncolys; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: PsiVac; Financial Interests, Institutional, Advisory Board: Replimune; Financial Interests, Institutional, Research Grant: Replimune. M. Tahara: Financial Interests, Personal and Institutional, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal and Institutional, Advisory Board: Ono Pharmaceutical; Financial Interests, Personal and Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Personal and Institutional, Invited Speaker: BMS; Financial Interests, Personal and Institutional, Advisory Board: BMS; Financial Interests, Personal and Institutional, Research Grant: BMS; Financial Interests, Personal and Institutional, Invited Speaker: MSD; Financial Interests, Personal and Institutional, Advisory Board: MSD; Financial Interests, Personal and Institutional, Research Grant: MSD; Financial Interests, Personal and Institutional, Invited Speaker: Bayer; Financial Interests, Personal and Institutional, Advisory Board: Bayer; Financial Interests, Personal and Institutional, Research Grant: Bayer; Financial Interests, Personal and Institutional, Invited Speaker: Merck Biopharma; Financial Interests, Personal and Institutional, Advisory Board: Merck Biopharma; Financial Interests, Personal and Institutional, Research Grant: Merck Biopharma; Financial Interests, Personal and Institutional, Invited Speaker: Eisai; Financial Interests, Personal and Institutional, Advisory Board: Eisai; Financial Interests, Personal and Institutional, Research Grant: Eisai; Financial Interests, Personal, Advisory Board: LOXO; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal and Institutional, Invited Speaker: Rakuten Medical; Financial Interests, Personal and Institutional, Advisory Board: Rakuten Medical; Financial Interests, Personal and Institutional, Research Grant: Rakuten Medical; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal and Institutional, Advisory Board: Novartis; Financial Interests, Personal and Institutional, Research Grant: Novartis. R.L. Ferris: Financial Interests, Personal, Advisory Board: Achilles Therapeutics; Financial Interests, Personal, Advisory Role: Aduro Biotech, Inc; Financial Interests, Institutional, Funding: AstraZeneca/MedImmune; Financial Interests, Personal, Advisory Role: Bicara Therapeutics, Inc; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Institutional, Funding: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Role: Everest Clinical Research Corporation; Financial Interests, Personal, Advisory Role: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Advisory Role: Genocea Biosciences, Inc; Financial Interests, Personal, Advisory Board: Instil Bio, Inc; Financial Interests, Personal, Advisory Role: Kowa Research Institute, Inc.; Financial Interests, Personal, Advisory Board: Lifescience Dynamics Limited; Financial Interests, Personal, Advisory Board: MacroGenics, Inc.; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Role: Mirati Therapeutics, Inc; Financial Interests, Personal, Advisory Role: Nanobiotix; Financial Interests, Personal, Advisory Role: Novasenta; Financial Interests, Personal, Stocks/Shares: Novasenta; Financial Interests, Institutional, Funding: Novasenta; Financial Interests, Personal, Advisory Board: Numab Therapeutics AG; Financial Interests, Personal, Advisory Board: OncoCyte Corporation; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Role: PPD; Financial Interests, Personal, Advisory Board: Rakuten Medical, Inc; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Board: Seagen, Inc; Financial Interests, Institutional, Funding: Tesaro; Financial Interests, Personal, Advisory Role: Zymeworks, Inc. M. Gillison: Financial Interests, Personal and Institutional, Advisory Role: Istari Oncology Inc; Financial Interests, Personal and Institutional, Advisory Role: LLX Solutions, LLC; Financial Interests, Personal and Institutional, Advisory Role: Kura Oncology; Financial Interests, Personal and Institutional, Advisory Role: Mirati Therapeutics; Financial Interests, Personal and Institutional, Advisory Role: BioNtech AG; Financial Interests, Personal and Institutional, Advisory Role: Shattuck Labs, Inc; Financial Interests, Personal and Institutional, Advisory Role: EMD Serono, Inc; Financial Interests, Personal and Institutional, Advisory Role: Depiopharm; Financial Interests, Personal and Institutional, Advisory Role: Merck & Co; Financial Interests, Personal and Institutional, Advisory Role: Ipsen Biopharmaceuticals Inc; Financial Interests, Personal and Institutional, Advisory Role: Gilead Sciences, Inc; Financial Interests, Personal and Institutional, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Advisory Role: Bicara Therapeutics; Financial Interests, Personal and Institutional, Advisory Role: Bayer Healthcare Pharmaceutics; Financial Interests, Personal and Institutional, Advisory Role: Genocea Biosciences, Inc.; Financial Interests, Personal and Institutional, Invited Speaker: OncLive; Financial Interests, Personal and Institutional, Invited Speaker: Roche; Financial Interests, Personal and Institutional, Advisory Role, Scientific advisory committee: Seagen; Financial Interests, Personal and Institutional, Advisory Role, Scientific advisory committee: Sensei Biotherapeutics, Inc; Financial Interests, Personal and Institutional, Funding, Research funding: Genocea Biosciences, Inc; Financial Interests, Personal and Institutional, Invited Speaker, Research funding: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Invited Speaker, Research funding: Genentech; Financial Interests, Personal and Institutional, Invited Speaker, Research funding: Kura; Financial Interests, Personal and Institutional, Invited Speaker, Research funding: Cullinan Labs; Financial Interests, Personal and Institutional, Other, DSBM: SQZBiotech; Financial Interests, Personal and Institutional, Other, DSBM: BioMimetix. J. Fayette: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Innate Pharma,; Financial Interests, Personal, Advisory Board: Merck Serono,; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Other, Research Funding: Seagens; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca . A. Daste: Financial Interests, Personal, Advisory Role, Consulting: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, Consulting: Merck, Sharp & Dohme; Financial Interests, Personal, Advisory Role, Consulting: Merck. R. Mesia Nin: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Merck, Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Merck, Sharp & Dohme; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Nanobiotics; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Boeringer Ingelheim. N.F. Saba: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Kura; Financial Interests, Personal, Advisory Board: CUE; Financial Interests, Institutional, Funding: Bristol Myers Squibb; Financial Interests, Institutional, Funding: Exelixis; Financial Interests, Personal, Advisory Role: Pfizer . M. Mak: Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Amgen. M.A. Álvarez Avitia: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Janssen Mexico; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Merck, Sharp & Dohme; Financial Interests, Personal, Advisory Board: Merck, Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Ipsen. A. Guminski: Financial Interests, Personal, Advisory Board: BMS; Non-Financial Interests, Personal, Other, Conference Travel Support: BMS; Financial Interests, Personal, Advisory Board: Regeneron; Non-Financial Interests, Personal, Principal Investigator: Regeneron; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Merck KgA; Non-Financial Interests, Personal, Other, Conference Travel Support: Merck KgA; Non-Financial Interests, Personal and Institutional, Principal Investigator, Investigator Initiated Trial Support: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Non-Financial Interests, Personal and Institutional, Research Grant: Sun Pharma; Financial Interests, Personal, Advisory Board: Sun Pharma. U. Müller-Richter: Non-Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Non-Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Non-Financial Interests, Institutional, Funding: Bristol Myers Squibb; Non-Financial Interests, Institutional, Principal Investigator: Bristol Myers Squibb; Non-Financial Interests, Personal, Invited Speaker: Merck, Sharp & Dohme; Non-Financial Interests, Personal, Advisory Board: Merck, Sharp & Dohme; Non-Financial Interests, Personal, Invited Speaker: Merck, Sharp & Dohme; Non-Financial Interests, Personal, Expert Testimony: Merck, Sharp & Dohme; Non-Financial Interests, Institutional, Funding: Merck, Sharp & Dohme; Financial Interests, Institutional, Principal Investigator: Merck, Sharp & Dohme; Non-Financial Interests, Personal, Advisory Board: Sanofi; Non-Financial Interests, Personal, Expert Testimony: Sanofi; Non-Financial Interests, Personal, Writing Engagements: Sanofi; Non-Financial Interests, Institutional, Funding: KuraOncology; Non-Financial Interests, Institutional, Principal Investigator: KuraOncology; Non-Financial Interests, Institutional, Funding: AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator: AstraZeneca; Non-Financial Interests, Institutional, Funding: BioNTech; Non-Financial Interests, Institutional, Principal Investigator: BioNTech. N. Kiyota: Financial Interests, Personal, Speaker’s Bureau, Speaker of sponsored seminar: Bayer; Financial Interests, Personal, Speaker’s Bureau, Speaker of sponsored seminar: Eisai; Financial Interests, Personal, Speaker’s Bureau, Speaker of sponsored seminar: ONO; Financial Interests, Personal, Speaker’s Bureau, Speaker of sponsored seminar: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau, Speaker of sponsored seminar: Merck, Sharp & Dohme; Financial Interests, Institutional, Research Grant: Adlai Nortye; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: ONO; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Rakuten Medical; Financial Interests, Institutional, Advisory Role: Adlai Nortye; Financial Interests, Institutional, Advisory Role: ONO. M. Roberts: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS . T.A. Khan: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. K. Miller-Moslin: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. L. Wei: Financial Interests, Personal, Full or part-time Employment: BMS. R. Robert Haddad: Financial Interests, Personal, Full or part-time Employment: Dana-Farber Cancer Institute; Financial Interests, Personal, Leadership Role: National Comprehensive Cancer Network; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Loxo; Financial Interests, Personal, Advisory Role: Genentech; Financial Interests, Personal, Advisory Role: Immunomic Therapeutics; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: Gilead Sciences; Financial Interests, Personal, Advisory Role: Vaccinex; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Personal, Advisory Role: BioNTech AG; Financial Interests, Personal, Advisory Role: Achilles Therapeutics; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Mirati Therapeutics; Financial Interests, Institutional, Funding, Research Funding: Boehringer Ingelheim; Financial Interests, Institutional, Funding, Research Funding: Merck; Financial Interests, Institutional, Funding, Research funding: Bristol Myers Squibb; Financial Interests, Institutional, Funding, Research funding: Celgene; Financial Interests, Institutional, Funding, Research funding: AstraZeneca; Financial Interests, Institutional, Funding, Research Funding: VentiRx; Financial Interests, Institutional, Funding, Research Funding: Genentech; Financial Interests, Institutional, Funding, Research Funding: Pfizer; Financial Interests, Institutional, Funding, Research Funding: Kura; Financial Interests, Personal, Other: Nanobiotix; Financial Interests, Personal, Other: ISA Pharmaceuticals; Financial Interests, Personal, Other, Patents, Royalties, Other Intellectual Property: UpToDate. All other authors have declared no conflicts of interest.
Invited Discussant LBA35 and LBA36
- Amanda Psyrri (Haidari, Greece)
Q&A and live discussion
- Amanda Psyrri (Haidari, Greece)
858O - Results of KEYNOTE-122: A phase III study of pembrolizumab (pembro) monotherapy vs chemotherapy (chemo) for platinum-pretreated, recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC)
- Anthony T.C. T. Chan (Sha Tin, Hong Kong PRC)
Abstract
Background
Treatment options for R/M NPC are limited. In the phase Ib KEYNOTE-028 trial, pembro showed antitumor activity and manageable safety in a cohort of 27 patients (pts) with R/M NPC. KEYNOTE-122 (NCT02611960) is a multicenter, open-label, randomized phase III study to evaluate the efficacy and safety of pembro monotherapy vs chemo in pts with platinum-pretreated, R/M NPC.
Methods
Pts with histologically confirmed non-keratinizing differentiated (WHO Class II) or undifferentiated (WHO Class III), platinum-pretreated, Epstein-Barr Virus positive R/M NPC, ECOG PS 0-1, and measurable disease per RECIST v1.1 were randomized 1:1 to pembro 200 mg Q3W for up to 35 cycles or investigator’s choice of standard doses of chemo (capecitabine [C], gemcitabine [G], or docetaxel [D]). Primary endpoint was OS (overall significance threshold: 0.025, one-sided). Secondary endpoints included PFS, ORR, and DOR (all per RECIST v1.1 by BICR).
Results
Between May 5, 2016 and May 28, 2018, 233 pts were randomized to pembro (N=117) or chemo (N=116; C: n=39; G, n=46; D, n=31). 74.4% pts in the pembro arm and 62.9% in the chemo arm had PD-L1 CPS≥1. Median time from the first dose to data cutoff (Nov 30, 2020) was 45.1 (range, 30.2-54.8) mo. In the ITT population, median OS was 17.2 months (95% CI, 11.7–22.9) with pembro and 15.3 months (10.9–18.1) with chemo (HR, 0.90; 95% CI, 0.67-1.19;
Conclusions
Pembro monotherapy did not improve OS vs chemo in pts with platinum-pretreated R/M NPC. PD-L1 CPS ≥1 did not enrich for OS or ORR for pembro. Pembro showed manageable safety and a lower incidence of treatment-related AEs vs chemo.
ITT population Pembro Chemo N=117 N=116 17.2 (11.7–22.9) 15.3 (10.9–18.1) HR (95% CI) 0.90 (0.67-1.19); 4.1 (2.1-5.6) 5.5 (4.0-8.1) HR (95% CI) 1.28 (0.94-1.75) 21.4 (14.3-29.9) 23.3 (15.9-32.0) 50.4 (41.0-59.8) 63.8 (54.4-72.5) 12.0 (1.7+-49.7+) 13.1 (2.6-49.3+) Patients with PD-L1 CPS≥1 n=87 n=73 17.2 (10.0-27.0) 18.0 (12.1-23.9) 23.0 (14.6-33.2) 26.0 (16.5-37.6)
Clinical trial identification
NCT02611960.
Editorial acknowledgement
Medical writing assistance was provided by Yue Liu 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
A.T.C.T.C. Chan: Financial Interests, Institutional, Research Grant: Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Eli Lilly, ; Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme, Merck Serono, Cullinan Management Inc., Beigene, Springer, Pfizer, ; Financial Interests, Personal, Other, Travel: Bristol Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche, Novartis, AstraZeneca; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, Tessa Therapeutics Ltd; Non-Financial Interests, Personal, Other: Immunomic Therpeutics, Inc Angene Biotechnology, Owlstone Medical Limited. V.H.F. Lee: Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Personal, Research Grant: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme. R. Hong: Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme. M. Ahn: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Takeda, Merck Sharp & Dohme, Ono, Bristol Myers Squibb, Lilly, Amgen, Merck, Roche; Financial Interests, Personal, Advisory Role: AstraZeneca, Takeda, Merck Sharp & Dohme, Ono, Bristol Myers Squibb, Lilly, Amgen, Merck, Roche, Alpha Pharmaceuticals; Financial Interests, Personal, Research Grant: AstraZeneca, Roche, Merck Sharp & Dohme. W.Q. Chong: Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel payment: Merck Sharp & Dohme, Amgen. S. Kim: Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant: Novartis, Sanofi Aventis, Dongkook Pharm Co; Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Lilly, DaeHwa Pharma Co.,Ltd, ISU Abix, Daiichi-Sankyo; Financial Interests, Personal, Stocks/Shares: Genopeaks, Neogene TC. H. Gwo Fuang: Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme, AstraZenenca, Eli Lily, Arcus Biosciences, Inc., Pfizer, INEX EpiTherapeutics Pte. Ltd., Roche, Astella, Novartis, Tessa Therapeutics, Regeneron, Samsung Bioepis; Financial Interests, Personal, Invited Speaker: Eli Lily, Merck, Pfizer; Financial Interests, Personal, Other, Travel Expenses: AstraZenenca, Bristol-Myers Squibb Pte Ltd; Financial Interests, Personal, Advisory Board: Pfizer, Boehringer ingelheim, AstraZenenca, MIMS, Merck Sharp & Dohme, Eli Lily. P.B. Caguioa: Financial Interests, Personal, Other, honoraria: Roche, AstraZeneca, Novartis, Merck Sharp & Dohme; Financial Interests, Institutional, Funding: Merck Sharp & Dohme. N. Ngamphaiboon: Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme, Roche, Exelixis, RAPT therapeutics, BeiGene, Pfizer; Financial Interests, Personal, Other, Honoraria: Roche, AstraZeneca, Amgen, Merck Sharp & Dohme, Taiho; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, Amgen, Novartis, Bayer, AstraZeneca, Claris, Elli-Lilly. C. Ho: Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Personal, Research Grant: AstraZeneca , Roche; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Bayer, Eisai, EMD Serono, Merck, Novartis, Roche; Financial Interests, Personal, Other, Travel Payments: Roche. M.A.S. Abdul Aziz: Financial Interests, Institutional, Funding: Merck Sharp & Dohme. Q.S. Ng: Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme. C. Yen: Financial Interests, Institutional, Funding: Merck Sharp & Dohme. N. Soparattanapaisarn: Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Personal, Research Grant: Merck Sharp & Dohme ; Financial Interests, Personal, Research Grant: AstraZeneca ; Financial Interests, Personal, Research Grant: Roche ; Financial Interests, Personal, Research Grant: Bristol Myers Squibb. K.C.R. Ngan: Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: Pfizer, Novartis, Sanofi, AstraZeneca, Lilly, Merck Sharp & Dohme, Zai Lab, Roche, Eisai; Financial Interests, Personal, Other, Honoraria: Novartis, AstraZeneca, Sanofi, Pfizer, Zai Lab, Eisai, Lilly, Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel payments: Pfizer, Astellas, Novartis, Merck Sharp & Dohme, Roche, Esiai, Merck, Sanofi, Bristol Myers Squibb, Zai Lab; Financial Interests, Personal, Advisory Board: Nuance Biotech (Shenzhen, China); Financial Interests, Personal, Leadership Role: President, Hong Kong Breast Oncology Group. S.K. Kho: Financial Interests, Institutional, Funding: Merck Sharp & Dohme. R. Swaby: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. S. Saraf: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. J. Ge: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. L.L. Siu: Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Bristol Myers Squibb; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Boerhinger-Ingelheim; Financial Interests, Institutional, Funding: GlaxoSmithKline; Financial Interests, Institutional, Funding: Roche/Genentech; Financial Interests, Institutional, Funding: Karyopharm; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Astellas; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: Abbvie; Financial Interests, Institutional, Funding: Amgen; Financial Interests, Institutional, Funding: Symphogen; Financial Interests, Institutional, Funding: Intensity Therapeutics; Financial Interests, Institutional, Funding: Mirati; Financial Interests, Institutional, Funding: Shattucks; Financial Interests, Institutional, Funding: Avid; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Morphosys; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Oncorus; Financial Interests, Personal, Advisory Role: Symphogen; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: Voronoi; Financial Interests, Personal, Advisory Role: Treadwell Therapeutics; Financial Interests, Personal, Advisory Role: Arvinas; Financial Interests, Personal, Advisory Role: Tessa; Financial Interests, Personal, Advisory Role: Navire; Financial Interests, Personal, Advisory Role: Relay; Financial Interests, Personal, Advisory Role: Rubius; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Janpix.
859O - Refining TNM staging system for Epstein-Barr virus-related nasopharyngeal carcinoma: A multicenter cohort study
- Wang-Zhong Li (Guangzhou, China)
Abstract
Background
Additional nonanatomic prognostic factors beyond TNM categories supplement evidence-based TNM classifications. We aimed to refine TNM staging groups for Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma (NPC) by incorporating the EBV DNA status.
Methods
This multicenter retrospective cohort comprised 2,354 patients with nonmetastatic NPC treated with radiotherapy with or without chemotherapy between January 2008 and December 2016. Progression-free survival (PFS) and overall survival (OS) according to EBV DNA status and the 8th edition TNM staging system were compared. Recursive partitioning analysis (RPA) combined with supervised clustering was applied to derive prognostic groupings. A refined RPA stage was developed, validated, and compared with existing staging schemes.
Results
Pretreatment EBV DNA status was an independent prognostic factor. Lower survival probability by higher TNM stage was evident in EBV DNA (+) patients but not in those with EBV DNA (-) disease. Integrating EBV DNA status and TNM stage, the RPA stage divided nonmetastatic NPC into RPA-I (T1-3N0 or EBV DNA [-] T1-3N1), RPA-II (EBV DNA [+] T1-3N1-2 or EBV DNA [-] T1-3N2-3/T4N0-3), and RPA-III (EBV DNA [+] T4N0-3/T1-3N3) with distinctly different prognosis. The RPA stage outperformed the current TNM stage and two reported RPA staging schemes. These results were internally and externally validated. The new staging system identified approximately two-fold low-risk patients that might not benefit from chemotherapy than the current TNM staging system.
Conclusions
We developed and validated an RPA-based staging system for EBV-related NPC. This staging system may facilitate prognostic stratification and clinical trial designs.
Legal entity responsible for the study
The authors.
Funding
National Natural Science Foundation of China; Guangdong Medical Research Foundation; Young Teacher Training Project of Sun Yat-sen University.
Disclosure
All authors have declared no conflicts of interest.
Invited Discussant 858O and 859O
- Lisa F. Licitra (Milan, Italy)
Q&A and live discussion
- Lisa F. Licitra (Milan, Italy)