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Editorial
. 2022 Aug 2;28(15):3173-3175.
doi: 10.1158/1078-0432.CCR-22-0932.

Impact of PD-1 Blockade in Nonresponders: Pitfalls and Promise

Harry H Yoon  1 , Haidong Dong  2 , Qian Shi  3
Affiliations
Editorial

Impact of PD-1 Blockade in Nonresponders: Pitfalls and Promise

Harry H Yoon et al. Clin Cancer Res. .

Abstract

Exploratory analysis of a phase III trial in esophageal cancer found that the patients who most contributed to an overall survival benefit from PD-1 blockade were not responders, but non-responders. The analysis has limitations but may have implications for investigating the optimal timing of immunotherapy relative to other treatments. See related article by Okada et al., p. 3277.

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Conflict of interest statement

Disclosure of conflict of interest

Dr. Harry H. Yoon reports relevant financial relationship(s) with industry (all honoraria paid to institution) OncXerna (advisory board), Merck (advisory board, steering committee), Zymeworks (advisory board), MacroGenics (advisory board, steering committee), BMS (advisory board), BeiGene (steering committee, advisory board, education symposium, research), and AstraZeneca (advisory board) and funding from Merck, BMS, MacroGenics, BeiGene, Boston Biomedical, Elevar Therapeutics, and CARsgen. Dr. Shi reports consulting/advisory role from Yiviva Inc, Boehringer Ingelheim Pharmaceuticals, Inc, Regeneron Pharmaceuticals, Inc., Hoosier Cancer Research Network, Honorarium/speaker role from Chugai Pharmaceutical Co., Ltd (to myself), research funds from Celgene/BMS, Roche/Genentech, Janssen, Novartis (to institution). Dr Dong reports no conflicts.

Figures

Figure
Figure. Apparent overall survival benefit from ICI in non-responders and its implications for future research.
On the left are results from the ATTRACTION-03 phase 3 trial in which patients with advanced esophageal squamous cell carcinoma were randomized to nivolumab vs taxane in the second-line setting. The primary endpoint of OS was met in the intent to treat population. Exploratory OS outcomes stratified by best response, usually determined within the first 1-4 months, are shown. Most of the OS benefit from ICI (vs chemotherapy) in the study was observed in patients whose best response was stable or progressive disease. Patients who lacked measurable lesions at baseline, 19% of the nivolumab arm, are not shown (survival curves not reported) and did not appear to contribute to nivolumab’s association with improved OS. In the middle (blue box) are potential explanations for the apparent OS benefit from ICI in patients whose best response was stable or progressive disease. Abbreviations: ICI, immune checkpoint inhibition; OS, overall survival.
See this image and copyright information in PMC

Comment on

References

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