Comparing the Efficacy of Cancer Therapies between Subgroups in Basket Trials

Cell Syst. 2020 Nov 18;11(5):449-460.e2. doi: 10.1016/j.cels.2020.09.003.


The need to test anticancer drugs in multiple indications has been addressed by basket trials, which are Phase I or II clinical trials involving multiple tumor subtypes and a single master protocol. Basket trials typically involve few patients per type, making it challenging to rigorously compare responses across types. We describe the use of permutation testing to test for differences among subgroups using empirical null distributions and the Benjamini-Hochberg procedure to control for false discovery. We apply the approach retrospectively to tumor-volume changes and progression-free survival in published basket trials for neratinib, larotrectinib, pembrolizumab, and imatinib and uncover examples of therapeutic benefit missed by conventional binomial testing. For example, we identify an overlooked opportunity for use of neratinib in lung cancers carrying ERBB2 Exon 20 mutations. Permutation testing can be used to design basket trials but is more conservatively introduced alongside established approaches to enrollment such as Simon's two-stage design.

Keywords: basket clinical trial; breast cancer; imatinib; larotrectinib; lung cancer; master protocol trial; neratinib; pembrolizumab; permutation test; targeted therapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Pharmacological / analysis*
  • Humans
  • Models, Statistical
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Research Design
  • Retrospective Studies
  • Treatment Outcome


  • Antineoplastic Agents
  • Biomarkers, Pharmacological