Adding Palifosfamide in Extensive-Stage SCLC Did Not Increase Survival

Adding palifosfamide to carboplatin and etoposide failed to improve survival over the latter two agents alone in patients with extensive stage (ES) small-cell lung cancer (SCLC), according to a new study.

“Platinum doublet chemotherapy has been the standard of care first-line regimen in patients with ES SCLC for the last 3 decades,” wrote study authors led by Shadia I. Jalal, MD, of the Indiana University Melvin and Bren Simon Cancer Center in Indianapolis. “Unfortunately, disease relapse occurs in all patients, and second-line chemotherapy options lead to short responses. Novel first-line therapies continue to be urgently needed.”

The MATISSE study was an open-label, adaptive phase III trial of 188 patients with ES SCLC; patients were randomized to receive either carboplatin and etoposide alone, or in combination with palifosfamide (94 patients in each group). Patients were a median age of 61 years, 70% were male, and approximately half were current smokers and just under 40% were former smokers. The results of the trial were published online ahead of print in the Journal of Clinical Oncology.

The median overall survival (OS) with palifosfamide was 10.03 months, which was similar to that with carboplatin and etoposide alone, at 10.37 months; this yielded a hazard ratio of 1.30 (95% CI, 0.95–1.78; P = .096), meaning the trial failed to meet its primary endpoint. Subgroup analyses showed no differences between the therapies except for patients aged 65 years or older; in those patients, those receiving the palifosfamide regimen had a median OS of 6.8 months, compared with 9.7 months without the agent (P = .044).

There were no differences with regard to the number of patients experiencing a serious adverse event (AEs) between the two study arms, with 26% of palifosfamide patients and 25% of carboplatin/etoposide patients experiencing at least one. Among the serious AEs reported were febrile neutropenia, pancytopenia, neutropenia, and nausea; none were observed in more than 5.5% of either study group, and the rates of each were similar.

The authors noted that the study failed to meet its patient accrual goals and was thus underpowered, but they wrote that it is “extremely unlikely” that the study would have been positive even with full accrual.

“Our understanding of the biology of SCLC has significantly increased, but translating that knowledge into new clinical therapeutic options that have an impact on the care of patients with SCLC has yet to be achieved,” they wrote. “Better first- and second-line treatment options for ES SCLC are necessary to transform the landscape of this bleak disease.”