Abstract
BackgroundThe 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.MethodsAll 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.ResultsIn 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.ConclusionPatients 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).
Highlights
In 2020, an estimated 1300 Canadians died from advanced melanoma [1]
Pulmonary metastases (M1b)/non-central nervous system visceral metastases (M1c) vs. metastases to skin or nonregional lymph nodes (M1a)(HR=1.50, 95% confidence interval (CI)=1.12-2.02; p=0.007) and pre-treatment Eastern Cooperative Oncology Group Performance Status (ECOG Eastern Cooperative Oncology Group performance status (PS)) >1 were associated with earlier treatment initiation (TTI)
In the phase III CheckMate 067 study, four cycles of nivolumab and ipilimumab followed by maintenance nivolumab resulted in a median overall survival (OS) of six years [6]; high grade immune-related adverse events (irAE) were documented in 42% of patients [7]
Summary
In 2020, an estimated 1300 Canadians died from advanced melanoma [1]. Melanoma typically arises from melanocytes in cutaneous locations, but uveal, acral, mucosal, and unknown primary melanoma are the recognized subtypes [2]. First-line immunotherapy treatment options for patients with advanced melanoma include monotherapy with anti-programmed cell death-1 (Anti-PD-1) antibodies such as nivolumab or pembrolizumab and combination treatment with nivolumab and ipilimumab (a cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody.) Median OS in KEYNOTE-006 (a phase III study of pembrolizumab versus ipilimumab) and CheckMate 066 (a phase III study of nivolumab versus dacarbazine chemotherapy) was approximately three. In the phase III CheckMate 067 study, four cycles of nivolumab and ipilimumab followed by maintenance nivolumab resulted in a median OS of six years [6]; high grade irAE were documented in 42% of patients [7]. 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
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