Topotecan or other agents as second-line therapy for relapsed small-cell lung cancer: A meta-analysis of randomized...

Small cell lung cancer (SCLC) is exceptionally responsive to chemotherapy and radiotherapy. In relapsed patients, particularly in resistant/refractory cases, the progression of disease occurs rapidly with second-line agents. Topotecan (TOPO), a camptothecin analog, is the only agent able to increase overall survival (OS) compared with the best supportive care alone. However, the efficacy of platinum-based chemotherapy rechallenge or other agents has not been systematically explored. In the present review, published articles, which evaluated outcome and toxicity associated with TOPO or non-TOPO-based chemotherapy in patients with SCLC from inception to September 2020 were systematically searched and identified by searching the PubMed, EMBASE and Cochrane Library databases. The primary outcome of interest was the risk of death (OS), and the secondary endpoints were risk of progression progression-free survival (PFS), overall response rate (ORR) and G3-4 hematological toxicities. A total of nine studies were included in quantitative synthesis for a total of 1,689 patients. They included platinum-based rechallenge, anthracycline-based combinations or camptothecin analogs. TOPO did not improve OS with respect to other therapies [hazard ratio (HR), 0.92; 95% confidence interval (95% CI), 0.78-1.09; P=0.33]. Similarly, PFS was similar in the two arms (HR, 1.1; 95% CI, 0.72-1.67; P=0.66). The ORR was not statistically higher with non-TOPO agents (relative risk, 1.53; 95% CI, 0.95-2.48). In subgroup analysis, combination chemotherapy was associated with an improved PFS but not OS or ORR compared with TOPO alone (HR, 1.85; 95% CI, 1.52-2.24; P<0.01). The rates of G3-4 anemia, febrile neutropenia and neutropenia were similar. In conclusion, in patients with relapsed SCLC, TOPO was associated with a similar survival, PFS and ORR as other agents. However, polychemotherapy was associated with improved PFS.