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. 2021 Jul:152:155-164.
doi: 10.1016/j.ejca.2021.04.035. Epub 2021 Jun 6.

Neoadjuvant immunotherapy is reshaping cancer management across multiple tumour types: The future is now!

Michele Maio  1 , Christian Blank  2 , Andrea Necchi  3 , Anna Maria Di Giacomo  4 , Ramy Ibrahim  5 , Michael Lahn  6 , Bernard A Fox  7 , R Bryan Bell  8 , Giampaolo Tortora  9 , Alexander M M Eggermont  10
Affiliations

Neoadjuvant immunotherapy is reshaping cancer management across multiple tumour types: The future is now!

Michele Maio et al. Eur J Cancer. 2021 Jul.

Abstract

The Italian Network for Tumor Biotherapy (Network Italiano per la Bioterapia dei Tumori [NIBIT]) Foundation hosted its annual 2020 Think Tank meeting virtually, at which representatives from academic, clinical, industry, philanthropic, and regulatory organisations discussed the role of neoadjuvant immunotherapy for the treatment of cancer. Although the number of neoadjuvant immunotherapeutic trials is increasing across all malignancies, the Think Tank focused its discussion on the status of neoadjuvant trials in cutaneous melanoma (CM), muscle-invasive urothelial bladder cancer (MIBC), head and neck squamous cell carcinoma (HNSCC), and pancreatic adenocarcinoma (PDAC). Neoadjuvant developments in CM are nothing short of trailblazing. Pathologic Complete Response (pCR), pathologic near Complete Response, and partial Pathologic Responses reduce 90-100% of recurrences. This is in sharp contrast to targeted therapies in neoadjuvant CM trials, where only a pCR seems to reduce recurrence. The pCR rate after neoadjuvant immunotherapy varies among the different malignancies of CM, MIBC, HNSCC, and PDAC and may be associated with different reductions of recurrence rates. In CM, emerging evidence suggests that neoadjuvant immunotherapy with anti-CTLA-4 plus anti-PD1 is a game changer in patients with palpable nodal Stage III or resectable Stage IV disease by curing more patients, reducing recurrences and the need for surgical interventions, such as lymph node dissections and metastasectomies. The Think Tank panel discussed future approaches on how to optimise results across different tumour types. Future approaches should include reducing monocyte-mediated (tumour-associated macrophages) and fibroblast-mediated (cancer-associated fibroblasts) barriers in the tumour microenvironment to facilitate the recruitment of immune cells to the tumour site, to reduce immune-suppressive mediators, and to increase antigen presentation at the site of the tumour.

Keywords: Biomarkers; Bladder cancer; CTLA-4; Head and neck cancer; Immunotherapy; Melanoma; Neoadjuvant trials; PD-1; PD-L1; Pancreatic cancer.

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Conflict of interest statement

Conflicts of interest statement M.M. was a consultant/advisory board member for Bristol Myers Squibb, Roche, Astra Zeneca, Merck Sharp Dohme, Philogen, Merck Serono, Glaxo Smith Kline, Sanofi, Pierre Fabre, Eli-Lilly, Amgen, Cosmos, Alfasigma, and owns shares of Epigen Therapeutics. C.B. received commercial research grants from Novartis, Bristol-Myers Squibb, and NanoString; is a paid advisory board member for Bristol-Myers Squibb, MSD, Roche, Novartis, GlaxoSmithKline, AstraZeneca, Pfizer, Lilly, GenMab, and Pierre Fabre; and holds ownership interest in Uniti Cars, Neon Therapeutics, and Forty Seven. A.N. received honoraria Roche, Merck, AstraZeneca, and Janssen Pharmaceuticals. A.M.D.G. was a consultant and/or advisor to Incyte, Pierre Fabre, Bristol Myers Squibb, Merck Sharp Dohme, and Sanofi and has received compensated educational activities from Bristol Myers Squibb, Merck Sharp Dohme, Pierre Fabre, and Sanofi. R.I. was a CMO at bitbio, BoD of bluebird and Surface oncology, and SAB member of Harpoon. M.L. was employed by iOnctura SA as Chief Medical Officer. B.F. received consulting fees from Turnstone Bio, PrimeVax, UltiVue, AstraZeneca, and Boehringer Ingelheim; conducted contracted research at Macrogenics, OncoSec, BMS, Akoya, NanoString, Incyte, Shimadzu, and Viralytics/Merck; was cofounder of and holds ownership interest in UbiVac. R.B.B. has received research funds from Bristol-Myers Squibb and is on the speakers bureau for Merck and Regeneron. He is an advisory board member for Macrogenics. G.T. was a consultant/advisory board member for Bristol Myers Squibb, Astra Zeneca, Merck Sharp Dohme, and Merck Serono. A.M.M.E. is/has been consultant/advisory board member for Biocad, BioInvent, BioNTech, BMS, CatalYm, Ellipses, GSK, ISA pharmaceuticals, Ellipses, GSK, IO Biotech, ISA pharmaceuticals, Merck&Co/MSD, Nektar, Novartis, Pfizer, Roche, Sellas, SkylineDx, RiverD, TigaTx, and TTxDiscovery.

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