The addition of pravastatin to standard chemotherapy did not improve overall survival or progression-free survival in treatment-naive patients with small-cell lung cancer (SCLC), a study published in the Journal of Clinical Oncology has shown.1
Preclinical studies have demonstrated that statins have additive effects with agents like cisplatin in inhibiting tumor growth, and observational studies have shown that statins combined with chemotherapy may delay relapse and prolong survival in various cancer types. Because treating SCLC remains challenging, researchers sought to evaluate whether adding a statin to chemotherapy improves outcomes in newly diagnosed patients with SCLC.
For the multicenter, double-blind, phase 3 LUNGSTAR trial (ClinicalTrials.gov Identifier: NCT00433498), investigators enrolled 846 patients with SCLC and a performance status of 0 to 3 from 91 hospitals in the United Kingdom. Of those, 43% had limited disease and 57% had extensive disease. Median age was 64 years.
Participants were randomly assigned to receive pravastatin 40 mg orally daily or placebo, in combination with up to 6 cycles of etoposide plus a platinum agent every 3 weeks, until disease progression or unacceptable toxicity.
Results showed no significant improvement in overall survival with pravastatin compared with placebo (hazard ratio, 1.01; 95% CI, 0.88-1.16; P = .90). Median overall survival was 10.6 months in the pravastatin arm vs 10.7 months in the control group; 13.2% (95% CI, 10.0-16.7) and 14.1% (95% CI, 10.9-17.7) of patients, respectively, were alive at 2 years.
Subgroup analyses also showed no benefit from pravastatin in several subgroups, including patients with limited disease and those with extensive disease. Among patients with limited SCLC, median overall survival was 14.6 months regardless of whether patients received pravastatin or placebo. Similarly, median survival was 9.1 months vs 8.8 months with pravastatin and placebo, respectively, in patients with extensive disease.
The study further demonstrated that median progression-free survival was 7.7 months in the pravastatin group vs 7.3 months in the control group. The safety profiles were comparable between the 2 treatment arms.
The findings suggest that statin therapy does not confer benefit to patients with SCLC receiving first-line chemotherapy with etoposide plus cisplatin or carboplatin. Researchers conducting studies to assess the benefit of statins in patients with cancer should ensure there is sufficient preclinical evidence to warrant large randomized trials.
1. Seckl MJ, Ottensmeier CH, Cullen M, et al. Multicenter, phase III, randomized, double-blind, placebo-controlled trial of pravastatin added to first-line standard chemotherapy in small-cell lung cancer (LUNGSTAR).J Clin Oncol. 2017 Feb 27. doi: 10.1200/JCO.2016.69.7391 [Epub ahead of print]