The addition of palifosfamide to carboplatin and etoposide failed to prolong survival among patients with extensive-stage small-cell lung cancer (SCLC), according to a study published in the Journal of Clinical Oncology.1

Relapse with standard-of-care carboplatin or cisplatin with etoposide occurs in all patients; median overall survival (OS) in this setting is 8 to 13 months. The purpose of this study was to determine if adding palifosfamide to the platinum doublet would improve outcomes in SCLC.

The open-label, phase 3 MATISSE trial ( Identifier: NCT01555710) randomly assigned 188 patients with previously untreated extensive-stage SCLC to receive carboplatin and etoposide with or without palifosfamide for 4 to 6 cycles.

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The median age at baseline was 61 and the majority of patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. Most patients were current (48%) or former (37%) smokers.

Median OS was similar in both treatment arms: 10.03 months (95% CI, 7.7-10.5 months) with palifosfamide compared with 10.37 months (95% CI, 8.7-13.4 months) with the doublet.

Patients aged 65 or older, however, demonstrated shortened survival, with a median OS of 6.8 months with palifosfamide compared with 9.7 months with the doublet (hazard ratio, 1.913; 95% CI, 1.151-3.177; P = .044).

Median OS remained similar when patients were stratified by sex performance status, and region of treatment.

The rate of serious adverse events was similar in the palifosfamide and doublet arms (28.3 vs 27.5%, respectively), with about 20% in each arm experiencing a treatment-emergent adverse event. About 50% of patients in each arm received the full 6 cycles of treatment.

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There was no documentation of dose delays or reductions, and not all adverse events were documented making it “difficult to make firm conclusions regarding the overall toxicity” of added palifosfamide, wrote the authors. 


  1. Jalal SI, Lavin P, Lo G, Lebel F, Einhorn L. Carboplatin and etoposide with or without palifosfamide in untreated extensive-stage small-cell lung cancer: a multicenter, adaptive, randomized phase III study (MATISSE). J Clin Oncol. 2017 Jun 12. doi: 10.1200/JCO.2016.71.7454 [Epub ahead of print]