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

Abstract

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.

Burden of chemotherapy‐induced myelosuppression among patients with extensive‐stage small cell lung cancer: A retrospective study from community oncology practices

“…Clinical trials have reported a wide range of incidence rates for grade 3/4 neutropenia, anemia, and thrombocytopenia with first‐line platinum/etoposide regimens, with or without immunotherapy 32–35 and for second‐line topotecan 36–38 . This study reported that chemotherapy‐induced myelosuppression was prevalent among patients in the real‐world community oncology setting; the most common any‐grade event being anemia, and the most common grade ≥ 3 event being neutropenia.…”

“…Clinical trials have reported a wide range of incidence rates for grade 3/4 neutropenia, anemia, and thrombocytopenia with first-line platinum/etoposide regimens, with or without immunotherapy [32][33][34][35] and for second-line topotecan. [36][37][38] This study reported that chemotherapy-induced myelosuppression was prevalent among patients in the real-world community oncology setting; the most common any-grade event being anemia, and the most common grade ≥ 3 event being neutropenia. Our findings are consistent with previous studies in the real-world setting, which have reported that grade ≥ 3 myelosuppressive AEs are common among patients with ES-SCLC treated with chemotherapy (56.6-64.1%) 39,40 grade with inpatient admission = 74.3%).…”

Unweaving the mitotic spindle: A focus on Aurora kinase inhibitors in lung cancer

“…Even after the introduction of immunotherapy in the first-line setting, the majority of patients with SCLC experiences an inexorable disease progression in less than 12 months ( 4 , 5 ). Unfortunately, effective treatments are not available after disease progression to first-line therapy: topotecan is currently the standard of care, with limited results ( 74 ). These poor outcomes highlight the need for a better molecular knowledge of the disease to develop new therapeutic strategies.…”

A Single-Arm Multi-Center Phase II Clinical Trial of Cadonilimab (anti-PD-1/CTLA-4) in Combination with or without Conventional Second-Line Treatment for Patients with Extensive Stage Small Cell Lung Cancer

“…Topotecan, the most widely used second-line agent globally, has limited efficacy and an unfavorable safety profile. 10 , 11 Lurbinectedin, in 2020 became the first drug approval by the FDA in over 20 years to second-line treatment, was conditionally approved based on an objective response rate (ORR) of 35%; however, a randomized study failed to demonstrate OS benefit. 12 No agent is specifically for second-line treatment of relapsed SCLC.…”