SHIVA02 Trial: Using Patients as Their Own Controls to Assess Efficacy of Therapies Based on Molecular Profiling in...

SHIVA02 is a tissue-agnostic precision medicine basket trial assessing a molecularly targeted strategy in patients with refractory cancer using patients as their own controls to assess the efficacy of the strategy.

Patients with cancers refractory to standard of care underwent molecular profiling and received standard therapy, followed, if possible, by matched therapy guided by a Molecular Biology Board. Tumor evaluations were performed every 2 months according to RECIST 1.1 on both treatments in order to reliably assess the progression-free survival (PFS) ratio.

Among 263 patients enrolled, molecular profiling was successful in 192 patients (73%), and 34 patients (13%) received matched therapy and were eligible for PFS ratio analyses. The median PFS1 was 2.1 months [95% confidence interval (CI), 1.8-3.6] and the median PFS2 was 2 months (95% CI, 1.8-2.7). A PFS ratio exceeding 1.3 or 1.5 was observed in 11 (32%) and 8 (24%) patients, respectively. Overall survival (OS) was prolonged in the subgroup of patients evaluable for PFS ratio. Prognostic factors such as Eastern Cooperative Oncology Group performance status and Royal Marsden Hospital score significantly influenced OS, highlighting the importance of patient selection in precision oncology trials.

Using a prospective and standardized approach for evaluating PFS on both standard and matched therapies, 32% of patients receiving matched therapy benefited from the approach with a PFS ratio >1.3.

The SHIVA02 trial evaluated molecularly guided anticancer therapy in patients with refractory cancer. To rigorously assess efficacy in this heterogeneous population, each patient served as their own control using the PFS ratio, comparing two consecutive PFS periods. Unlike previous studies relying on limited or retrospective PFS1 data, SHIVA02 prospectively assessed both periods according to RECIST 1.1 criteria, providing the first trial specifically designed for robust evaluation of the PFS ratio.