P2.03a-008 Relative Dose Intensity of First-Line Chemotherapy and Overall Survival in Patients With Advanced Non–Small-Cell Lung Cancer (NSCLC)

Abstract

For patients with advanced NSCLC, chemotherapy dose reductions/delays are commonly used to manage toxicities. However, there is limited information on the relationship between relative dose intensity (RDI) and survival in metastatic NSCLC. Objective: Describe the relationship between RDI and survival in patients with NSCLC in a US community oncology practice setting. This was a retrospective study using the McKesson Specialty Health/US Oncology iKnowMedSM electronic health record database. Inclusion criteria: Patients with advanced (stage III/IV) NSCLC who initiated first-line, intravenous, myelosuppressive chemotherapy between January 2007 and December 2010. Endpoints: Mean RDI (a composite measure including both dose delays and dose reductions), RDI <85%, and incidences of dose delays ≥7 days and dose reductions ≥15% in any chemotherapy cycle. Dosing analysis covered a period up to 6 months after chemotherapy initiation. Uni-variable and multivariable analyzes for survival were conducted using Cox proportional hazard regression. Overall, 3866 patients with NSCLC were included; the most common chemotherapy regimens included carboplatin/taxol (n=1733), pemetrexed/carboplatin (n=789), and bevacizumab/carboplatin/taxol (n=734). 709 (18.3%) received colony-stimulating factor primary prophylaxis. The mean (SD) RDI was 83.9% (28.5%), the incidence of RDI <85% was 40.4%, and the incidence of dose delays ≥7 days and dose reductions ≥15% were 32.4% and 50.1%, respectively. Uni-variable analysis suggested that dose delay ≥7 days was associated with a 22.4% reduction in the risk of death (P<0.0001). Multivariable analysis suggested that RDI and dose delay were significant predictors of survival after controlling for covariates. RDI <85% and dose delay ≥7 days were associated with a 17.6% increase and a 29.0% reduction in risk of death, respectively (Table). Reduced RDI and chemotherapy dose delays were common in advanced NSCLC and significantly associated with survival in a multivariable analysis. Understanding the complex effect of dose intensity on outcomes will be important for managing toxicities and improving survival.TableMultivariable Cox Regression Analysis for Overall Survival for Patients with Lung CancerVariableHR (95%CI)P ValueRDI <85% (reference: ≥85%)1.176 (1.047–1.320)0.0062Dose delay ≥7 days (reference: <7 days)0.710 (0.630–0.800)<0.0001ECOG performance status (reference: status of 0)11.316 (1.192–1.453)<0.000121.654 (1.350–2.027)<0.0001Hemoglobin <12 g/dL (reference: ≥12 g/dL)1.098 (0.993–1.213)0.0686Tumor subgroups (reference: squamous)Adenocarcinoma0.783 (0.698–0.877)<0.0001Other0.932 (0.725–1.199)0.5855ECOG=Eastern Cooperative Oncology Group; HR=hazard ratio; RDI=relative dose intensity. Open table in a new tab