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22 december 2021: ESMO 2021

Immuuntherapie met nivolumab plus ipilimumab bij mond- en keelkanker geeft nog betere resultaten dan standaard immuuntherapie plus chemotherapie bij mond- en keelkanker type plaveiselcarcinoom.

Zo blijkt uit de internationale fase III CheckMate 651-studie, die dit jaar op ESMO 2021 = het European Society for Medical Oncology Congress werd gepresenteerd door Dr. Haddad en collega's. Zij vergeleken nivolumab en ipilimumab met het EXTREME-regime = Cetuximab + Cisplatin/Carboplatin + Fluorouracil bij de eerstelijnsbehandeling van recidiverend of uitgezaaide mond- en keelkanker van het type plaveiselcelcarcinoom. Net als in de KEYNOTE-048 studie had ongeveer 40% van de patiënten in dit onderzoek een CPS 20 score (lichamelijke en geestelijke conditie) en ongeveer 75% een CPS score ≥ 1.

Bij patiënten met een PD-L1 expressie en een CPS 20 score of een CPS ≥1 geeft nivolumab/ipilimumab betere resultaten in vergelijking met de patiënten die het EXTREME-regiem kregen, zowel in betere algehele overleving en duur van de respons.
De mediane totale overleving was respectievelijk 17,6 maanden versus 14,6 maanden (CPS 20) en 15,7 versus 13,2 maanden (CPS ≥ 1). Hoewel dit geen statistische significantie bereikte, "is de totale overleving van 17,6 maanden met nivolumab/ipilimumab de beste die we hebben gezien in een gerandomiseerde fase III-studie voor die groep patiënten", aldus dr. Haddad. "Een groot percentage - bijna de helft van de patiënten die deelnamen aan de 'EXTREME'-arm - kreeg een checkpointremmer in de tweedelijnsbehandeling en dit heeft een grote impact gehad op de algehele overleving in het onderzoek," verklaarde Dr. Haddad.

Met nivolumab/ipilimumab reageerde meer dan de helft van de responders na 18 maanden nog steeds in beide patiëntenpopulaties. De combinatie van checkpointremmers had ook de neiging de verslechtering van de symptomen te vertragen; het verbeterde ook klinisch de algehele gezondheidsstatus in vergelijking met het EXTREME-regime bij de populatie met een CPS 20 score. Het veiligheidsprofiel was ook gunstig in vergelijking met EXTREME.

Kernpunten uit de studie:

Checkpointblokkade is de nieuwe zorgstandaard voor patiënten met CPS-positieve recidiverende of gemetastaseerde hoofd-halskanker.
Nivolumab plus ipilimumab vertoont activiteit in deze patiëntenpopulatie, hoewel significante cross-over naar checkpointremmers in het CheckMate 651-onderzoek ervoor zorgde dat de experimentele arm geen statistische significantie bereikte.
Het gebruik van de combinatie van een checkpointremmer en cetuximab behoeft nader onderzoek.

Bij patiënten met terugkerende ziekte die definitieve therapie hebben gehad maar nog steeds een chirurgische optie hebben, was de combinatie van nivolumab en het experimentele anti-KIR monoklonale antilichaam lirilumab ook veelbelovend, volgens Dr. Haddad. "Denk aan uw patiënten met strottenhoofdkanker die zijn behandeld met bestraling en chemotherapie, die nu een recidief hebben en een operatie zullen moeten ondergaan", legde hij uit.

In een fase II-onderzoek kregen patiënten met terugkerende hoofd-halskanker die geacht werden een chirurgische optie te hebben een cyclus van nivolumab/lirilumab gevolgd door een operatie en daarna 6 maanden van hetzelfde regime. Herbestraling was niet toegestaan.
De 1-jaars ziektevrije overleving bij deze patiënten was 55%. "We zijn van mening dat dit een veelbelovend regime is dat verder onderzoek waard is", zei hij. “Een van de belangrijke eindpunten waar we naar zochten, was of de operatie zou worden uitgesteld, maar er was geen vertraging bij de bergingsoperatie; binnen 2 weken na de eerste dosis immunotherapie konden we patiënten geopereerd krijgen.”

Een ander recent gepubliceerd onderzoek dat werd opgemerkt door Dr. Haddad, onderzocht pembrolizumab plus cetuximab bij de eerstelijnsbehandeling van terugkerende of uitgezaaide hoofd-halskanker. Het totale responspercentage was 45% en bijna de helft van de patiënten die deelnamen aan het onderzoek had een lage PD -L1 CPS < 1.
"Dit is veel hoger dan het responspercentage dat u in deze omgeving zult zien met pembrolizumab als enkel middel", voegde hij eraan toe. “Eerlijk gezegd was dit een verrassend resultaat voor mij en voor velen van ons in het veld. Deze gegevens zijn veelbelovend en verder onderzoek waard.”

Dit zijn de referenties die behoren bij genoemde studie, zie abstract daaronder:

REFERENCES

1. Haddad RI: Optimizing the use of check point inhibitors in recurrent metastatic SCCHN. 2021 Updates in the Management of Head & Neck Cancer. Presented November 6, 2021.

2. Vermorken JB, Mesia R, Rivera F, et al: Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 359:1116-1127, 2008.

3. Burtness B, Harrington KJ, Greil R, et al: Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): A randomised, open-label, phase 3 study. Lancet 394:1915-1928, 2019.

4. Argiris A, Harrington K, Tahara M, et al: Nivolumab + ipilimumab vs -EXTREME regimen as first-line treatment for recurrent/metastatic squamous cell carcinoma of the head and neck: Final results of CheckMate 651. ESMO Congress 2021. Abstract LBA36. Presented September 20, 2021.

5. Hanna GJ, ONeill A, Shin KY, et al: Neoadjuvant and adjuvant nivolumab and lirilumab in patients with recurrent, resectable squamous cell carcinoma of the head and neck. Clin Cancer Res. October 19, 2021 (early release online).

6. Sacco AG, Chen R, Worden FP, et al: Pembrolizumab plus cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma. Lancet Oncol 6:883-892, 2021.

M SCCHN): Final results of CheckMate 651

Date

20 Sep 2021

Session

Proffered Paper session - Head and neck cancer, excl. thyroid

Presenters

Athanassios Argiris

Citation

Annals of Oncology (2021) 32 (suppl_5): S1283-S1346. 10.1016/annonc/annonc741

Authors

A. Argiris1, K. Harrington2, M. Tahara3, R.L. Ferris4, M. Gillison5, J. Fayette6, A. Daste7, P. Koralewski8, R. Mesia Nin9, N.F. Saba10, M. Mak11, M.A. Álvarez Avitia12, A. Guminski13, U. Müller-Richter14, N. Kiyota15, M. Roberts16, T.A. Khan17, K. Miller-Moslin18, L. Wei19, R. Robert Haddad20

Author affiliations

Resources

Abstract LBA36

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] P = 0.4951) or CPS ≥20 (HR 0.78 [97.5% CI: 0.59–1.03] P = 0.0469) populations. In pts with CPS ≥1, OS HR was 0.82 (95% CI: 0.69–0.97). Other efficacy results are in the table. Overall, 8% (N+I) and 46% (EXTREME) of pts received subsequent immunotherapy. Grade 3/4 tx-related adverse events occurred in 28% vs 71% of treated pts, respectively.

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. Table: LBA36

	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
P value	0.4951	0.0469	-
2-y OS, %	31	28	41	33	34	28
Median PFS, mo95% CI	3.32.8−4.2	6.75.8−7.0	5.43.1–6.9	7.05.6–8.7	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	16.69.7−29.4	5.95.5−7.0	32.612.1−NR	7.05.7−10.1	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.

mond- en keelkanker, immuuntherapie, nivolumab + ipilimumab, checkmate 651, EXTREME studie