Checkpoint Inhibitors, Palliative Care, or Hospice

Checkpoint (CTLA-4, PD-1, and PD-L1) inhibitors have changed the face of oncology. A subset of patients enjoys long, gratifying treatment responses. Unfortunately, most patients do not respond even when expressing favorably markers such as PD-L1. Checkpoint inhibitors are largely palliative (though a subset have long-term cancer responses) and as such patient-related outcome measures should be included when evaluating benefits. The purpose of this review is to place checkpoint inhibitor trials within a palliation context. Included is a discussion on potential adverse effects on end-of-life care.

Pivotal studies have presented efficacy and safety data but we have little published data on quality of life or symptom responses. Extension of life is approximately 2-3 months with some long-term responses in a minority of patients. The cost of checkpoint inhibitors is high for utility (as measured by quality-adjusted life-year saved) and ranges from 81,000 to over 200,000 USD for quality-adjusted life-year saved. Adverse effects were suboptimally reported in multiple studies. Meaningful responses in many trials as defined by the European Society of Medical Oncology are modest. Because at least for now, checkpoint inhibitors are used in advanced cancer and largely palliative patients should be seen by palliative specialists, symptoms related to cancer assessed, and advanced directives addressed. Treatment-related autoimmune diseases represent toxicities which oncologists and palliative specialists must understand. This means that palliative care specialists should know about the benefits and adverse effects of these agents. Whether checkpoint inhibitors increase or decrease aggressive care, hospice referrals, and costs at the end of life is yet to be determined.