 Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinomaJoris L. Vos,
Joris B. W. Elbers,
Oscar Krijgsman,
Joleen J. H. Traets,
Xiaohang Qiao,
Anne M. Leun,
Yoni Lubeck,
Iris M. Seignette,
Laura A. Smit,
Stefan M. Willems,
Michiel W. M. Brekel,
Richard Dirven,
M. Baris Karakullukcu,
Luc Karssemakers,
W. Martin C. Klop,
Peter J. F. M. Lohuis,
Willem H. Schreuder,
Ludi E. Smeele,
Lilly-Ann Velden,
I. Bing Tan,
Suzanne Onderwater,
Bas Jasperse,
Wouter V. Vogel,
Abrahim Al-Mamgani,
Astrid Keijser,
Vincent Noort,
Annegien Broeks,
Erik Hooijberg,
Daniel S. Peeper,
Ton N. Schumacher,
Christian U. Blank,
Jan Paul Boer,
John B. A. G. Haanen and
Charlotte L. Zuur ()
Nature Communications, 2021, vol. 12, issue 1, 1-13 Abstract: Abstract Surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) results in 30‒50% five-year overall survival. In IMCISION (NCT03003637), a non-randomized phase Ib/IIa trial, 32 HNSCC patients are treated with 2 doses (in weeks 1 and 3) of immune checkpoint blockade (ICB) using nivolumab (NIVO MONO, n = 6, phase Ib arm A) or nivolumab plus a single dose of ipilimumab (COMBO, n = 26, 6 in phase Ib arm B, and 20 in phase IIa) prior to surgery. Primary endpoints are feasibility to resect no later than week 6 (phase Ib) and primary tumor pathological response (phase IIa). Surgery is not delayed or suspended for any patient in phase Ib, meeting the primary endpoint. Grade 3‒4 immune-related adverse events are seen in 2 of 6 (33%) NIVO MONO and 10 of 26 (38%) total COMBO patients. Pathological response, defined as the %-change in primary tumor viable tumor cell percentage from baseline biopsy to on-treatment resection, is evaluable in 17/20 phase IIa patients and 29/32 total trial patients (6/6 NIVO MONO, 23/26 COMBO). We observe a major pathological response (MPR, 90‒100% response) in 35% of patients after COMBO ICB, both in phase IIa (6/17) and in the whole trial (8/23), meeting the phase IIa primary endpoint threshold of 10%. NIVO MONO’s MPR rate is 17% (1/6). None of the MPR patients develop recurrent HSNCC during 24.0 months median postsurgical follow-up. FDG-PET-based total lesion glycolysis identifies MPR patients prior to surgery. A baseline AID/APOBEC-associated mutational profile and an on-treatment decrease in hypoxia RNA signature are observed in MPR patients. Our data indicate that neoadjuvant COMBO ICB is feasible and encouragingly efficacious in HNSCC. Date: 2021 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26472-9 Ordering information: This journal article can be ordered from DOI: 10.1038/s41467-021-26472-9 Access Statistics for this article Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie More articles in Nature Communications from Nature |
Is your work missing from RePEc? Here is how to contribute.
Questions or problems? Check the EconPapers FAQ or send mail to .
EconPapers is hosted by the
School of Business at Örebro University.