Abstract

While there is no approved third line chemotherapy option for small cell lung cancer (SCLC), empiric use of chemotherapy is common in this setting in the absence of supporting prospective data. In order to assess the potential benefit and predictors of chemotherapy use beyond the second line setting in SCLC, we analyzed the SEER-MEDICARE database. We employed data of SCLC patients diagnosed between 1985 and 2005. Univariate (UVA) association of line of chemotherapies with covariates was examined with Wilcoxon rank-sum test, chi-square or Fisher’s exact test. Multivariable (MVA) logistic regression analysis for line of therapy was conducted using the following covariates: year of diagnosis, age, gender, race, Medicare status, urban/rural location, and radiation. Survival functions were estimated by the Kaplan-Meier method and the log-rank test was used to assess for difference in overall survival (OS) stratified by line of therapy. UVA and MVA survival analyses were carried out using the Cox proportional hazards model. To further balance confounders between patients receiving different lines of therapy, propensity scores were estimated using a MVA logistic regression model to predict the receipt of 3rd line chemotherapy based on relevant covariates. Propensity score analysis was further conducted by including the estimated propensity score as a covariate in a Cox proportional hazards model. All analyses were done using SAS 9.3 with two-sided tests and a significant level of 0.05. There were 47,351 patients with SCLC of which 23,535 (49.7%) received chemotherapy and 10,887 (23%) received platinum-based chemotherapy. Of the platinum-treated patients, 1424 (13.1%) received additional salvage therapy of either topotecan alone (n=801) or topotecan and additional treatments as 3rd line and beyond (n=623). The median OS was 11, 13, 15 and 17 months respectively for patients treated with one, two, three or > 3 lines of chemotherapy respectively. Propensity score analysis showed additional lines of therapy beyond the second line was associated with a reduced risk of death (HR: 0.786; 0.729 - 0.847, p<0.001 and 0.617; 0.564 - 0.675; p<0.001 for 3rd line and > 3 lines of therapy respectively). Age (p=0.043) and year of diagnosis (P<0.001) were significantly associated with treatment beyond 2nd line topotecan on MVA analysis. Salvage chemotherapy is not commonly used following failure of platinum containing chemotherapy in SCLC patients. However, chemotherapy beyond the second line was associated with an incremental survival benefit in US MEDICARE-eligible SCLC patients.

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