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Review
. 2021 Mar;9(3):e001901.
doi: 10.1136/jitc-2020-001901.

Considerations for treatment duration in responders to immune checkpoint inhibitors

Thomas U Marron  1 , Aideen E Ryan  2 , Sangeetha M Reddy  3 , Sabina Kaczanowska  4 , Rania H Younis  5   6 , Dipti Thakkar  7 , Jiajia Zhang  8 , Todd Bartkowiak  9 , Rachel Howard  10 , Kristin G Anderson  11   12 , Daniel Olson  13 , Abdul Rafeh Naqash  14 , Ravi B Patel  15 , Esha Sachdev  16 , Maria E Rodriguez-Ruiz  17 , Michal Sheffer  18 , Sarah Church  19 , Christopher Fuhrman  19 , Abigail Overacre-Delgoffe  20 , Rosa Nguyen  21 , Vaia Florou  22 , Jessica E Thaxton  23   24   25 , David H Aggen  26 , Jennifer L Guerriero  27   28
Affiliations
Review

Considerations for treatment duration in responders to immune checkpoint inhibitors

Thomas U Marron et al. J Immunother Cancer. 2021 Mar.

Abstract

Immune checkpoint inhibitors (ICIs) have improved overall survival for cancer patients, however, optimal duration of ICI therapy has yet to be defined. Given ICIs were first used to treat patients with metastatic melanoma, a condition that at the time was incurable, little attention was initially paid to how much therapy would be needed for a durable response. As the early immunotherapy trials have matured past 10 years, a significant per cent of patients have demonstrated durable responses; it is now time to determine whether patients have been overtreated, and if durable remissions can still be achieved with less therapy, limiting the physical and financial toxicity associated with years of treatment. Well-designed trials are needed to identify optimal duration of therapy, and to define biomarkers to predict who would benefit from shorter courses of immunotherapy. Here, we outline key questions related to health, financial and societal toxicities of over treating with ICI and present four unique clinical trials aimed at exposing criteria for early cessation of ICI. Taken together, there is a serious liability to overtreating patients with ICI and future work is warranted to determine when it is safe to stop ICI.

Keywords: Costimulatory and Inhibitory T-Cell Receptors; Immunotherapy; Melanoma; Review.

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Conflict of interest statement

Competing interests: TM is a consultant for AstraZeneca, Genentech, Boehringe Ingelheim, Atara, and Regeneron. And receives research grant support from Bristol Myers Squibb, Regeneron, Merck, and Boehringer Ingelheim. AER receives sponsored research support from Janssen, AbbVie, Bristol Myers Squibb, Celgene SMR receives consulting fees from Eli Lilly, Daiichi Sankyo and Silverback Therapeutics and research support from Cancer Prevention and Research Institute of Texas RR190020. MER-R receives research grant support from ROCHE and Highlight Therapeutics. SC and CF are employees and shareholder at NanoString Technologies. DHA has received royalties from the University of Illinois and has received consulting fees from Boehringer Ingelheim. JG is a consultant for Glaxo-Smith Kline (GSK), Array BioPharma, Codagenix, Verseau Therapeutics and Kymera and receives sponsored research support from GSK, Eli Lilly and Array BioPharma.

Figures

Figure 1
Figure 1
Patients receiving immune checkpoint inhibitors without progressive disease are treated for an undefined period, which can extend several years and may impose both financial and physical toxicity. Clinical trials are needed to determine criteria that would allow potential early cessation and monitoring thus eliminating both financial and physical toxicities. CR, complete response; ctDNA, circulating tumor DNA; PR, partial response; SD, stable disease.
Figure 2
Figure 2
Ongoing prospective clinical trials to determine criteria for early discontinuation of immune checkpoint inhibitors. CR, complete response; MTR, maximal tumor response; PR, partial response; SD, stable disease.
See this image and copyright information in PMC

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