Time to Treatment With Nivolumab or Pembrolizumab for Patients With Advanced Melanoma in Everyday Practice

Background The anti-programmed cell death one antibodies (Anti-PD-1 Ab) pembrolizumab or nivolumab are commonly prescribed to patients with advanced melanoma. The purpose of the current study is to identify baseline clinical characteristics associated with time to treatment initiation (TTI) of pembrolizumab or nivolumab for advanced melanoma and whether treatment delays are associated with differences in survival outcomes. Methods All patients receiving Anti-PD-1 Ab as a first-line treatment for advanced melanoma outside of clinical trials at British Columbia Cancer Agency between 10/2015 and 10/2019 were identified retrospectively. TTI was defined as the interval from pathologic diagnosis of advanced melanoma to first Anti-PD-1 Ab treatment. To determine the association between TTI and baseline characteristics, multivariable Cox proportional hazard regression analyses provided an estimate of the instantaneous relative risk of starting treatment at any time point (hazard ratio (HR(>1 indicates shorter TTI). To describe changes in overall survival (OS) observed for each four-week delay in treatment initiation, multivariable cox proportional hazard regression modelling was also performed. Results In a cohort of 302 patients, the median TTI was 52 days (interquartile range 30.2-99.0). Pulmonary metastases (M1b)/non-central nervous system visceral metastases (M1c) vs. metastases to skin or non-regional lymph nodes (M1a)(HR=1.50, 95% CI=1.12-2.02; p=0.007) and pre-treatment Eastern Cooperative Oncology Group Performance Status (ECOG PS) >1 (vs 0/1, HR=1.50, 95% CI= 1.11-2.01; p=0.008) were associated with earlier TTI. An association between treatment delay and improved OS was observed. Conclusion Patients having visceral metastases and poor baseline ECOG PS were more likely to initiate Anti-PD-1 Ab sooner. The association of shorter TTI with worse OS likely represents confounding by indication (urgent treatment offered to patients with aggressive disease).