Clinical outcome and toxicity for immunotherapy treatment in metastatic cancer patients.

Abstract

Immunotherapy (IO) is known to improve survival and outcome in various types of solid tumours. However, nonspecific activation of the immune system also affects various organ systems leading to the immune-related adverse events (irAEs). Systematic reviews of IO trials show that the actual incidence of irAEs may be higher than expected. Little is known about the impact of these irAEs on patients' clinical outcome, palliative care (PC) needs and hospice service use. This is a single centre, retrospective review study of metastatic cancer patients between June 2016 to June 2017 who consecutively received immune checkpoint inhibitors with anti-PD1 in our institution. The computerized medical record, body weight chart, blood test results and in-patient assessment records were reviewed. The study was approved by the Institutional Review Board of the University of Hong Kong/ Hospital Authority Hong Kong West Cluster and conducted in compliance with the Declaration of Helsinki. Fifty patients received immune checkpoint inhibitors with anti-PD1 consecutively between June 2016 to June 2017 were retrospectively reviewed. The median age was 64 years old (range: 22 to 87 years old). Thirty-three of them were male (66%) patients. Twenty-five patients (50%) experienced any grade irAE. Ten patients (20%) experienced grade III/IV irAE among which 7 patients (14%) discontinued IO treatment permanently and 2 patients (4%) died due to grade III/IV toxicity. The development of grade III/ IV irAE required in-patient management, with a median duration of hospitalization of 6.5 days (range: 1 to 38 days). The response rate was 36% vs. 4% (P=0.01), median PFS (15.8 vs. 6.2 months, P=0.26), median OS (21.0 vs. 12.9 months, P=0.05) for patients with or without irAEs, respectively. The occurrence of any grade irAE was associated with a trend of improved overall survival (OS) on IO (P=0.05). Five patients (10%) developed hyper-progressive disease and received only one course of treatment before they died. Only 2 patients (4%) developed pseudo-progressive disease during treatment. Thirty-five mortalities (70%) occurred at the time of assessment of the study, of which 18 patients (36%) received PC consultations and 12 patients (24%) received hospice care before they passed away. Our study underscored the need for enhanced selection criteria to identify patient subgroups which benefit most from IO, and the need to involve PC and hospice services early for those non-responders or unlikely responders. Patient education and a dedicated multi-disciplinary team approach is needed to identify and treat irAE timely to prevent severe morbidities and mortalities.