A systematic analysis of efficacy of second-line chemotherapy in sensitive and refractory small-cell lung cancer

Abstract

Introduction: Small-cell lung cancer (SCLC) patients unresponsive or relapsing within 90 days after frontline chemotherapy have poor prognosis and are treated with regimens different from the first-line regimen. Potential differences in the efficacy of second-line therapy for refractory and sensitive SCLC have not been well studied.

Methods: Studies that enrolled sensitive and refractory (relapse < 90 days or > 90 days) SCLC patients for second-line therapy were identified using electronic databases (MEDLINE, EMBASE, and Cochrane library), and meeting abstracts databases. A systematic analysis was conducted using Comprehensive Meta Analysis (version 2.2.048) software to calculate the odds ratio of response and 95% confidence interval. Median overall survival time for sensitive and resistant SCLC patients was compared by two-sided Student's t test. We tested for significant heterogeneity by Cochran's chi-square test and I-square index.

Results: Twenty-one studies published between 1984 and 2011 were eligible for this analysis with a total of 1692 patients enrolled; 912 with sensitive and 780 with refractory SCLC. The overall response rate was 17.9% with a higher response rate of 27.7% (range, 0%-77%) for sensitive SCLC versus 14.8% (range, 0%-70%) for refractory patients; p=0.0001. Pooled overall odds ratio of response was 2.235 (95% confidence interval: 1.518-3.291; p=0.001) favoring patients with sensitive disease. Median overall survival time was 6.7 months with a weighted survival of 7.7 and 5.4 months for sensitive and refractory SCLC, respectively (p = 0.0035).

Conclusions: Refractory SCLC patients derive modest clinical benefit from second-line chemotherapy. However, response and survival outcomes are superior with chemosensitive disease.

Figures

Figure 1

Consort diagram detailing search strategy and study selection for this systematic analysis

Figure 2

Forest plot showing the primary analysis using a random effect model for Odds ratio of response to salvage chemotherapy between patients with sensitive disease or refractory SCLC as defined based on response to frontline chemotherapy

Figure 3

Forest plot of analysis using a fixed effect model for Odds ratio of response to salvage chemotherapy between patients with sensitive disease or refractory SCLC as defined based on response to frontline chemotherapy.

Figure 4

Forest plot showing the result of Odds ratio analysis after excluding large studies that enrolled 50 or more patients

Figure 5

Forest plot of the result of systematic analysis for Odds ratio of response to salvage chemotherapy after excluding studies that evaluated topotecan

Figure 6

Forest plot of the result of systematic analysis for Odds ratio of response to salvage chemotherapy after excluding studies that evaluated combination multi-agent therapy

Figure 7

Forest plot of the result of systematic analysis for Odds ratio of response to salvage chemotherapy after excluding studies that evaluated single agent treatment regimens