Immunotherapy use outside clinical trial populations: never say never?

Abstract

Background: Based on favourable outcomes in clinical trials, immune checkpoint inhibitors (ICIs), most notably programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors, are now widely used across multiple cancer types. However, due to their strict inclusion and exclusion criteria, clinical studies often do not address challenges presented by non-trial populations. Design: This review summarises available data on the efficacy and safety of ICIs in trial-ineligible patients, including those with autoimmune disease, chronic viral infections, organ transplants, organ dysfunction, poor performance status, and brain metastases, as well as the elderly, children, and those who are pregnant. In addition, we review data concerning other real-world challenges with ICIs, including timing of therapy switch, relationships to radiotherapy or surgery, re-treatment after an immune-related toxicity, vaccinations in patients on ICIs, and current experience around ICI and coronavirus disease-19. Where possible, we provide recommendations to aid the oftendifficult decision-making process in those settings. Conclusions: Data suggest that ICIs are often active and have an acceptable safety profile in the populations described above, with the exception of PD-1 inhibitors in solid organ transplant recipients. Decisions about whether to treat with ICIs should be personalised and require multidisciplinary input and careful counselling of patients with respect to potential risks and benefits. Clinical judgements need to be carefully weighed, considering factors such as underlying cancer type, feasibility of alternative treatment options, or activity in trial-eligible patients.

Immune checkpoint inhibitor administration during pregnancy: a case series

“…Overall, 487 articles were identified and screened. After removal of 471 irrelevant articles, 9 reviews 10 , 11 , 12 , 23 , 24 , 25 , 26 , 27 , 28 and 3 non-English articles, 13 , 14 , 15 4 studies were considered eligible for our review. 29 , 30 , 31 , 32 Having investigated the references of the relevant reviews and eligible articles, two more articles were added.…”

“…Reviews of literature were not included, however we checked all the references of relevant reviews for eligible studies. 10 , 11 , 12 Language restrictions were applied (only articles in English were considered eligible). 13 , 14 , 15 While working separately, two researchers (AA and AMK) collected and analyzed data from each eligible study.…”

How aging of the global population is changing oncology

“…Demand will remain strong in all older patient groups for treatment modalities which are perceived, rightly or wrongly, to offer more hope of durable disease control with acceptable toxicity – e.g., molecularly-targeted drugs [ 92 ] and immune checkpoint inhibitors [ 93 ]. The spectrum of tumors in physiologically older patients tends to be more responsive to immunotherapies [ 94 ], even if only in a minority [ 95 ], whereas those in the physiologically younger group more often respond to hormonal or targeted drug therapies [ 96 ]. The higher educational profile of physiologically younger patients [ 97 , 98 ] will likely favor interest in personalized oncology – i.e., targeted ‘smart drugs’ which are scientifically plausible [ 99 ] but not always empirically testable [ 100 , 101 ].…”

Treatment of Cutaneous Squamous Cell Carcinoma with Immune Checkpoint Inhibitors in Special Populations

“…A large systematic review on SOT recipients undergoing ICIs due to advanced solid cancer confirmed the rejection rate of approximately 40%, similar across the type of ICIs and primary tumor histology [13]. An important issue is how to reduce risk of organ rejection without affecting immunotherapy efficacy: lowering or withdrawing immunosuppressive regimens is possible, however this needs to be discussed in multidisciplinary tumor board [14,15]. Intriguingly, immune-suppressive agents used in combination with corticosteroids could modulate the risk of organ rejection.…”