Time trend in treatment-related deaths of patients with advanced non-small-cell lung cancer enrolled into phase III trials of systemic treatment

Abstract

PurposeDespite recent improvements in supportive care, treatment-related death (TRD) remains a serious problem for lung cancer patients undergoing systemic chemotherapy. However, few studies have formally assessed possible changes in the TRD rate over the past two decades. Patients and methodsWe searched phase III trials to address the role of systemic treatment of advanced non-small-cell lung cancer (NSCLC). Time trend was assessed using linear regression analysis. ResultsThe overall incidence of TRD was calculated from 119 trials including 263 chemotherapy arms (46477 patients), with information about the causes of deaths available for 197 arms (75%, 30147 patients). Cisplatin-based regimens were the most frequently investigated. The crude TRD rate in the overall cohort of 119 trials was 1.26% and has been notably consistent over the investigated time (P = 0.762). The most common cause of death was febrile neutropenia, with no significant change in its incidence over the years (P = 0.139). In contrast, deaths due to renal toxicity decreased significantly (P = 0.042), whereas deaths due to pulmonary disorder increased significantly (P = 0.007). Among the pharmacological agents investigated, docetaxel (Taxotere) and epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) were associated with relatively high rates of deaths from pulmonary disorders, but EGFR-TKIs were not associated with death from any other cause. ConclusionsDespite of potential confounders in our results, the overall TRD rate has remained low, but not negligible, in phase III trials for advanced NSCLC, over the past two decades. Notably, the incidence and pattern of TRD stratified by cause have changed considerably.