Trends in Phase II Trials for Cancer Therapies

SIMPLE SUMMARY: Through time we have optimized drug combinations to treat cancer. Today we count with a better arsenal of cancer drugs acting on specific genes, known as targeted cancer therapies. Targeted therapies were promising as single drugs, avoiding the inevitable side effects of drug combinations. Here we determine whether that promise have been fulfilled. We collected data from thousand clinical trials testing the response of cancer drugs, either one drug at the time, or as part of a combination of drugs. We find that targeted therapies are better for the treatment of cancer when used in combination with previous cancer drugs that do not target specific genes. We conclude that drug combinations should continue as the standard of care for cancer therapy. ABSTRACT: Background: Drug combinations are the standard of care in cancer treatment. Identifying effective cancer drug combinations has become more challenging because of the increasing number of drugs. However, a substantial number of cancer drugs stumble at Phase III clinical trials despite exhibiting favourable efficacy in the earlier Phase. Methods: We analysed recent Phase II cancer trials comprising 2165 response rates to uncover trends in cancer therapies and used a null model of non-interacting agents to infer synergistic and antagonistic drug combinations. We compared our latest efficacy dataset with a previous dataset to assess the progress of cancer therapy. Results: Targeted therapies reach higher response rates when used in combination with cytotoxic drugs. We identify four synergistic and 10 antagonistic combinations based on the observed and expected response rates. We demonstrate that recent targeted agents have not significantly increased the response rates. Conclusions: We conclude that either we are not making progress or response rate measured by tumour shrinkage is not a reliable surrogate endpoint for the targeted agents.