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.
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.
Positive trial for the newest ADC on the block, Dato-DXd, is an ADC that delivers a topoisomerase I inhibitor payload via a TROP2 antibody. PFS was not impressive but favored DDxd at 4.4 vs 3.7 months in the docetaxel arm. This drug is now approved in metastatic breast cancer.
Pembrolizumab in addition to chemotherapy DID NOT help, recall now we have new approval for those patients (datopotamab).
Superior to osi (23 vs 16 progression-free survival). This is more toxic though, but seems manageable. Could this be a new first line standard of care? Also, this includes brain penetration data.
Adding SBRT improves local control and disease progression in the brain but not overall survival. Do the radiation oncologists have input? Is it worth it to control symptoms?
Neoadjuvant Osimertinib did not have a significant impact on major pathologic response and there were no ypCR’s after a median of ~8 weeks of therapy. I do think this shows a measurable response, enough such that I would consider Osi in a patient with “borderline resectable” disease.
FCS Hematology Oncology Review creates a platform for our physician network to observe the most recent articles and studies available in the oncology and hematology world. By sharing these articles we are building our wealth of knowledge of new observations and treatments as they come available.
