Comparison of tumor-agnostic and tumor-specific clinical oncology trial designs: a systematic review and meta-analysis

Tweetable abstractFor BRAF-altered advanced cancers, tumor-agnostic clinical trials do not yield substantially different results from tumor-specific studies and may offer a more efficient method for efficacy across multiple tumor types simultaneously, with less between-study heterogeneity. Plain language summaryTwo types of studies were sought, including studies that measured health outcomes in patients who were selected to receive medicine based on the location of their cancer (tumor), called tumor-specific studies; and studies that measured health outcomes in patients who were selected to receive cancer medicine regardless of the location of their cancer (tumor), called tumor-agnostic studies. From the studies found, only the studies that tested a specific type of cancer medicine (called tyrosine kinase inhibitors) on cancers with a specific genetic alteration (called BRAF-altered cancers) were identified. These studies were included in the analysis. The goal of the analysis was to determine if the two types of studies gave similar estimates of response rate, which is a type of trial outcome that measures whether the cancer shrinks or disappears. To do this, the results from the tumor-specific studies were combined with the results of the tumor-agnostic studies. No meaningful differences in the results from the tumor-specific studies compared with the tumor-agnostic studies were found. This suggests that tumor-specific studies do not yield very different results from tumor-agnostic studies. Aim: To examine whether tumor-specific and tumor-agnostic oncology trials produce comparable estimates of objective response rate (ORR) in BRAF-altered cancers. Materials & methods: Electronic database searches were performed to identify phase I-III clinical trials testing tyrosine kinase inhibitors from 2000 to 2021. A random-effects model was used to pool ORRs. A total of 22 cohorts from five tumor-agnostic trials and 41 cohorts from 27 tumor-specific trials had published ORRs. Results: There was no significant difference between pooled ORRs from either trial design for multitumor analyses (37% vs 50%; p = 0.05); thyroid cancer (57% vs 33%; p = 0.10); non-small-cell lung cancer (39% vs 53%; p = 0.18); or melanoma (55% vs 51%; p = 0.58). Conclusion: For BRAF-altered advanced cancers, tumor-agnostic trials do not yield substantially different results from tumor-specific trials.

Automated summary

For BRAF-altered advanced cancers, tumor-agnostic trials do not yield significantly different results from tumor-specific trials and may offer a more efficient method for evaluating efficacy across multiple tumor types simultaneously, with less heterogeneity between studies.