De-Escalation Strategies With Immune Checkpoint Blockers in Non–Small Cell Lung Cancer: Do We Already Have Enough Evidence?

Author(s): Jordi Remon, MD, PhD1; Martina Bortolot, MD2,3; Paolo Bironzo, MD, PhD1,4; Francesco Cortiula, MD5,6; Jessica Menis, MD7; Mariana Brandao, MD, PhD8; Jarushka Naidoo, MD9; Robin van Geel, PharmD, PhD10,11; Noemi Reguart, MD, PhD12; Oscar Arrieta, MD13; Giannis Mountzios, MD, PhD14; Lizza E.L. Hendriks, MD, PhD2; Benjamin Besse, MD, PhD1
Source: https://doi.org/10.1200/JCO-24-02347
Original Article
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Dr. Anjan Patel's Thoughts

Very thought-provoking review of immune checkpoint blockade therapy and strategies to possibly de-escalate therapy in the future. Could we reduce doses, extend dose intervals or diminish the duration of treatment? There is some (low-level) data supporting these ideas. However, ongoing prospective studies, mostly being done in countries with nationalized systems, will be informative on these topics. Expect interest in this topic to increase in a couple of years.

ABSTRACT

Immune checkpoint blockers (ICBs) have revolutionized the treatment of non–small cell lung cancer (NSCLC). Currently, one-dose-fits-all maximalist regimens have been considered the standard of care, with ICBs administered at flat doses regardless of patients’ weight. Treatment duration with ICBs is often arbitrary across stages, ranging from a fixed time point to until disease progression or unacceptable toxicity. However, the pharmacokinetic and pharmacodynamic properties of ICBs differ significantly from those of traditional cytotoxic drugs and the approved and selected doses on the basis of the maximum tolerated dose are often overestimated as there is limited evidence supporting a direct relationship between therapeutic intensity and outcomes. This can lead to overtreatment of patients, resulting in an increased risk of toxicity without enhanced efficacy. In addition, the use of these drugs is associated with significant costs that burden the global health care system and exacerbate disparities in access to care. De-escalating treatment by reducing the dose, duration, and frequency of administration of ICBs could optimize treatment efficacy, reduce toxicities, improve patients’ quality of life, and even decrease costs. Ultimately, de-escalation strategies may help to reduce treatment inequalities and to improve drug access worldwide. The aim of this review is to summarize and discuss the main issues and challenges regarding the de-escalation of ICBs in patients with NSCLC, focusing on dose-intensity reduction and treatment duration selection. Moreover, we assess the economic impact of implementing de-escalation approaches.

Author Affiliations

1Department of Cancer Medicine, Gustave Roussy, Villejuif, France; 2Department of Pulmonary Diseases, Maastricht University Medical Centre+, GROW Research Institute for Oncology and Reproduction, Maastricht, the Netherlands; 3Department of Medicine (DMED), University of Udine, Udine, Italy; 4Department of Oncology, University of Turin, Turin, Italy; 5Department of Radiation Oncology (Maastro), Maastricht University Medical Centre (+), GROW Research Institute for Oncology and Reproduction, Maastricht, the Netherlands; 6University Hospital of Udine, Department of Oncology, Udine, Italy; 7Medical Oncology Department, University and Hospital Trust of Verona, Verona, Italy; 8Institute Jules Bordet—Hôpital Universitaire de Bruxelles, Brussels, Belgium; 9Beaumont Hospital and RCSI University of Health Sciences, Dublin, Ireland; 10Department of Clinical Pharmacy & Toxicology, Maastricht University Medical Centre+, Maastricht, the Netherlands; 11CARIM School for Cardiovascular Disease, Maastricht University, Maastricht, the Netherlands; 12Department of Oncology, Hospital Clinic de Barcelona, Barcelona, Spain; 13Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico; 14Fourth Department of Medical Oncology and Clinical Trials Unit, Henry Dunant Hospital Center, Athens, Greece;

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