Chemo Combo Increases Survival, Toxicity in Sensitive Relapsed SCLC

Cisplatin, etoposide, and irinotecan outperformed topotecan as second-line chemotherapy in patients with sensitive relapsed small-cell lung cancer (SCLC) in a Japanese trial, though there was substantially increased toxicity with the regimen.

“Topotecan is the only drug approved in the United States and the European Union for relapsed SCLC,” said Koichi Goto, MD, PhD, of the National Cancer Center Hospital East in Chiba, Japan. He presented results of the new trial at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. Sensitive relapse refers to cancers that respond to initial chemotherapy and relapse more than 3 months after completion of that therapy, while refractory cancers do not respond initially or relapse within that 3 month window.

The new trial included 180 patients divided evenly between the cisplatin, etoposide, and irinotecan (PEI) group; and the topotecan group. More than 75% of patients were male and the median age was 64 years. The median time from completion of first-line therapy to relapse or progression was 148 days in the topotecan group and 181 in the PEI group.

The primary endpoint of overall survival was significantly better with PEI, at 18.2 months vs 12.5 months for topotecan, for a hazard ratio of 0.67 (95% CI, 0.51-0.88; P = .0079). The median progression-free survival was also better, at 5.7 months vs 3.6 months, for an HR of 0.50 (95% CI, 0.37-0.68; P < .0001). The objective response rate was 84.3% with PEI and only 26.7% with topotecan (P < .01); there were 9 complete responses and 61 partial responses with PEI compared with 0 and 23 with topotecan.

Serious toxicities, however, were substantially worse with the PEI regimen. Grade 3 or 4 leukopenia occurred in 80% of PEI patients vs 51.1% of topotecan patients; grade 3/4 anemia occurred in 84.4% and 27.8% of the two groups. There was also more grade 3/4 diarrhea (7.8% vs 0%) and febrile neutropenia (31.1% vs 6.7%). There were two treatment-related deaths in the topotecan group and one in the PEI group.

In spite of the increase in toxicity, Goto said the increase in survival means that “the combination chemotherapy with cisplatin, etoposide, and irinotecan should be considered as the standard second-line treatment for sensitive relapsed SCLC.”

Lee Krug, MD, of Memorial Sloan Kettering Cancer Center in New York, was the discussant for the presentation and said that the longer survival in both arms of the trial suggests that this could have been a highly selected group of patients. The toxicity, he added, is important in this case.

“We’ve reached a therapeutic plateau with our current chemotherapy options,” Krug said. “I think that we’re going to need to explore some new innovative strategies in order to make any real significant differences in this disease.”