SHIVA: molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer

SHIVA was an open-label randomised phase 2 trial at eight French academic centres. Adults with any metastatic solid tumour that had progressed on standard treatment had a mandatory biopsy of a metastasis and large-scale genomic testing. Those with an alteration in one of three pathways (hormone receptor, PI3K/AKT/mTOR, RAF/MEK) that could be matched to one of ten regimens of 11 marketed targeted drugs were randomised 1:1 to the matched drug, used outside its indication, or to treatment at the physician's choice.

Of 741 patients screened between October 2012 and July 2014, 293 (40 per cent) had a matchable alteration and 195 (26 per cent) were randomised, 99 to matched treatment and 96 to control. Median progression-free survival was 2.3 months with matched treatment and 2.0 months with physician's choice (hazard ratio 0.88, 95 per cent confidence interval 0.65 to 1.19, p 0.41). Grade 3 to 4 adverse events occurred in 43 per cent of patients on targeted drugs and 35 per cent on chemotherapy. The authors concluded that off-label use of targeted drugs should be discouraged and enrolment in trials encouraged.