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Learning from clinical trials of neoadjuvant checkpoint blockade

Abstract

Neoadjuvant checkpoint inhibition, in which the therapy is administered before surgery, is a promising new approach to managing bulky but resectable melanoma, and is also being explored in other cancers. This strategy has a high pathologic response rate, which correlates with survival outcomes. The fact that biopsies are routinely available provides a unique opportunity for understanding the responses to therapy and carrying out reverse translation in which these data are used to select therapies in the clinic or in trials that are more likely to improve patient outcomes. In this Perspective, we discuss the rationale for neoadjuvant immunotherapy in resectable solid tumors based on preclinical and human translational data, summarize the results of recent clinical trials and ongoing research, and focus on future directions for enhancing reverse translation.

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Fig. 1: Neoadjuvant and adjuvant approaches to immunotherapy.

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Acknowledgements

G.V.L. is supported by an NHMRC Practitioner Fellowship and the University of Sydney Medical Foundation.

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J.M.V. wrote the first draft of the review and processed writing and suggestions by the coauthors. This was done under supervision of, and final inspection by, G.V.L. and C.U.B.

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Correspondence to Christian U. Blank.

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J.M.V. declares no conflict of interests. Both G.V.L. and C.U.B. declare no direct conflicts with this work. For unrelated conflicts, G.V.L. is a consultant advisor to Aduro, Amgen, BMS, Mass-Array, Pierre-Fabre, Novartis, MERCK MSD and Roche. C.U.B. has received research funding from BMS, Novartis and NanoString; has an advisory role for BMS, MSD, Roche, Novartis, GSK, AZ, Pfizer, Lilly, GenMab, Pierre Fabre and Third Rock Ventures; and is a stock owner of Uniti Cars, Neon Therapeutics and Forty Seven.

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Versluis, J.M., Long, G. & Blank, C.U. Learning from clinical trials of neoadjuvant checkpoint blockade. Nat Med 26, 475–484 (2020). https://doi.org/10.1038/s41591-020-0829-0

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