Adding Pravastatin To Chemotherapy Has ‘No Survival Value’ For SCLC Patients

A large randomised trial did not show a survival benefit for the addition of pravastatin to chemotherapy for patients with limited or extensive small-cell lung cancer

medwireNews: LUNGSTAR results may rule out a role for use of pravastatin alongside platinum-based chemotherapy in patients with small-cell lung cancer (SCLC), finding no evidence for a clinical benefit.

The primary endpoint of overall survival was comparable in the 422 statin-treated patients and the 424 placebo-treated controls, at a median of 10.6 and 10.7 months, respectively, with corresponding 2-year rates of 13.2% and 14.1%.

And further analysis failed to find a significant benefit with pravastatin 40 mg/day for subgroups of patients with limited disease or extensive disease, report Michael Seckl, from Imperial College London in the UK, and co-investigators.

The secondary endpoint of progression-free survival also did not significantly differ between the pravastatin and placebo groups, at a median of 7.7 versus 7.3 months. The 2-year rates were 7.5% and 7.2%, respectively.

The researchers note that patients in the pravastatin and placebo groups had a comparable length of time on treatment (8.6 vs 7.8 months) and received a similar number of chemotherapy cycles of etoposide plus cisplatin or carboplatin, with 57% of both groups given the maximum six cycles. The distribution of grade 3 and more severe side effects was also comparable, with neutropenia being the most common event, affecting 44.9% and 43.0% of patients, respectively.

The phase III LUNGSTAR trial included 846 patients from 91 UK hospitals, all of whom had limited or extensive SCLC and a performance status of 0–3, and is the largest randomised study of statin therapy in cancer to date, the researchers say.

They comment in the Journal of Clinical Oncology that the preclinical evidence before LUNGSTAR was “sufficient, though not considered overwhelming by some” for the launch of phase II and III trials.

The investigators suggest that the choice of statin, dose or limited understanding of the purported mechanism of action may explain the LUNGSTAR trial’s negative results, but they emphasize that their “conclusions are the same as those found in all four much smaller, randomized, placebo-controlled trials specifically designed to evaluate statin therapy in patients with cancer.”

Seckl et al therefore recommend that “independent monitoring committees of studies that are still recruiting or in follow-up should examine interim analyses of clinical end points and stop early if there is sufficient evidence for futility, thus saving resources.”

But they caution: “Trials of statins in patients with cancer, which require an unexposed control group, will become more difficult to conduct because the usual age group of patients with cancer (middle and old age) already take them, as seen in LUNGSTAR, in which 22% of screened patients were ineligible because they were recent or current statin users.” 

Reference

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; Advance online publication 27 February. DOI: http://dx.doi.org/10.1200/JCO.2016.69.7391

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