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. 2022 Aug;10(8):e005036.
doi: 10.1136/jitc-2022-005036.

Neoadjuvant immunotherapy of locoregionally advanced solid tumors

Ahmad A Tarhini  1 , Jennifer R Eads  2 , Kathleen N Moore  3 , Valerie Tatard-Leitman  4 , John Wright  5 , Patrick M Forde  6 , Robert L Ferris  7
Affiliations

Neoadjuvant immunotherapy of locoregionally advanced solid tumors

Ahmad A Tarhini et al. J Immunother Cancer. 2022 Aug.

Abstract

Definitive management of locoregionally advanced solid tumors presents a major challenge and often consists of a combination of surgical, radiotherapeutic and systemic therapy approaches. Upfront surgical treatment with or without adjuvant radiotherapy carries the risks of significant morbidities and potential complications that could be lasting. In addition, these patients continue to have a high risk of local or distant disease relapse despite the use of standard adjuvant therapy. Preoperative neoadjuvant systemic therapy has the potential to significantly improve clinical outcomes, particularly in this era of expanding immunotherapeutic agents that have transformed the care of patients with metastatic/unresectable malignancies. Tremendous progress has been made with neoadjuvant immunotherapy in the treatment of several locoregionally advanced resectable solid tumors leading to ongoing phase 3 trials and change in clinical practice. The promise of neoadjuvant immunotherapy has been supported by the high pathologic tumor response rates in early trials as well as the durability of these responses making cure a more achievable potential outcome compared with other forms of systemic therapy. Furthermore, neoadjuvant studies allow the assessment of radiologic and pathological responses and the access to biospecimens before and during systemic therapy. Pathological responses may guide future treatment decisions, and biospecimens allow the conduct of mechanistic and biomarker studies that may guide future drug development. On behalf of the National Cancer Institute Early Drug Development Neoadjuvant Immunotherapy Working Group, this article summarizes the current state of neoadjuvant immunotherapy of solid tumors focusing primarily on locoregionally advanced melanoma, gynecologic malignancies, gastrointestinal malignancies, non-small cell lung cancer and head and neck cancer including recent advances and our expert recommendations related to future neoadjuvant trial designs and associated clinical and translational research questions.

Keywords: Gastrointestinal Neoplasms; Genital Neoplasms, Female; Head and Neck Neoplasms; Immunotherapy; Melanoma.

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Conflict of interest statement

Competing interests: AAT reports grants from Bristol Myers Squib, grants from Genentech-Roche, grants from Regeneron, grants from Sanofi-Genzyme, grants from Nektar, grants from Clinigen, grants from Merck, grants from Acrotech, grants from Pfizer, grants from Checkmate, grants from OncoSec, personal fees from Bristol Myers Squibb, personal fees from Merck, personal fees from Easai, personal fees from Instil Bio, personal fees from Clinigin, personal fees from Regeneron, personal fees from Sanofi-Genzyme, personal fees from Novartis, personal fees from Partner Therapeutics, personal fees from Genentech/Roche, personal fees from BioNTech, outside the submitted work. RLF reports grants from AstraZeneca/MedImmune, grants from Bristol Myers Squibb, grants from Merck, grants from Novasenta, grants from Tesaro, stock from Novasenta, personal fees from Aduro Biotech, personal fees from Bicara Therapeutics, personal fees from Bristol Myers Squibb, personal fees from Brooklyn Immunotherapeutics, personal fees from Catenion, personal fees from Coherus BioSciences, personal fees from Everest Clinical Research Corporation, personal fees from F. Hoffmann-La Roche, personal fees from Genocea Biosciences, personal fees from Hookipa Biotech, personal fees from Instil Bio, personal fees from Kowa Research Institute, personal fees from Lifescience Dynamics Limited, personal fees from MacroGenics, personal fees from Merck, personal fees from Mirati Therapeutics, personal fees from Mirror Biologics, personal fees from Nanobiotix, personal fees from Novasenta, personal fees from Numab Therapeutics AG, personal fees from OncoCyte Corporation, personal fees from Pfizer, personal fees from PPD Development LP, personal fees from Rakuten Medical, personal fees from Sanofi, personal fees from Seagen, personal fees from Vir Biotechnology, personal fees from Zymeworks, outside of the submitted work. KNM reports advisory board participation and reimbursement from Aravive, Alkemeres, AstraZeneca, Blueprint pharma, Eisai, EMD/Serono, GSK/Tesaro, Genentech/Roche, Hengrui, Immunogen, IMXmed, IMab, Lilly, Mersana, Mereo, Myriad, Merck, Novarits, OncXerna, Onconova, VBL Therapeutics. Research funding from PTC therapeutics, Lilly, Merck, GSK/Tesaro. GOG Partners Associate director. VT-L does not have any competing interest to report. PMF reports advisory board participation and reimbursement from Amgen, AstraZeneca, BMS, Daiichi, F-Star, G1, Genentech, Iteos, Janssen, Merck, Novartis, Sanofi, Surface, and research grants to his institution from AstraZeneca, BioNTech, BMS, Corvus, Kyowa, Novartis, and Regeneron. JRE reports employment at Bristol Meyers Squibb (spouse) and Janssen (spouse), honoraria for Pfizer, consulting for Lexicon, advisory boards for Ipsen, Advanced Accelerator Applications, and research support from Xencor, Tarveda, Genentech, Amgen, AstraZeneca, Medimmune, Hutchison, Incyte, Oncolys, Seagen. Neither JW nor members of his immediate family have a financial interest or obligation related to the information transmitted in this publication. None of them have received any compensation, salary, gifts, promises of employment or reimbursement for travel.

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