The use of molecularly targeted agents outside of their indications did not improve progression-free survival compared with physician treatment of choice in heavily pretreated patients with cancer, according to an online article published online ahead of print in The Lancet Oncology.1

Increased off-label use of molecular agents in patients whose tumors harbor the matching molecular alterations has been reported. Investigators performed a study to assess the efficacy of several molecularly targeted agents, which were chosen on the basis of molecular profiling but used outside of their indications in patients with advanced cancer for whom standard-of-care therapy had failed.

A total of 741 patients with any tumor type were screened, and 293 (40%) had at least one molecular alteration matching one of the 10 available regimens.

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At the time of data cutoff, 195 patients had been randomly assigned to the experimental group (n=99) and 96 in the control group. Median follow up was 11.3 months (IQR 5.8-11.6) in the experimental group and 11.3 months (IQR 8.1-11.6) in the control group at the time of primary progression-free survival analysis.

Median progression-free survival was 2.3 months (95% CI: 1.7-3.8) in the experimental group versus 2.0 months (95% CI: 1.8-2.1) in the control group (HR 0.88; 95% CI: 0.65-1.19; P=0.41).

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In the safety population, 43% of 100 patients treated with a molecularly targeted agent and 35% of 91 patients of 91 patients treated with cytotoxic chemotherapy experienced grade 3-4 adverse events (P=0.30).

The investigators concluded that “Off-label use of molecularly targeted agents should be discouraged, but enrollment in clinical trials should be encouraged to assess predictive biomarkers of efficacy.


  1. Le Tourneau C, Delord J-P, Gavoille C, et al. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. [published online ahead of print September 2, 2015]. Lancet Oncol. doi: 10.1016/S1470-2045(15)00188-6.