There is a very low success rate among anticancer agents in the drug development process, particularly between stage 2 and 3 clinical trials. There is a noticeably lower success rate for oncology drugs to progress from one clinical trial to the next (57%) as compared to non-oncology medications. Researchers at the Sloan Kettering Cancer Center in New York attempted to look for possible explanations for the phenomenon. What they hypothesize is that the ability of clinical trials to predict the efficacy of novel drugs is inaccurate due to the outdated methods of determining end point response in solid tumors. They assert that the current methods used, most notably the Response Evaluation Criteria in Solid Tumors (RECIST), were developed decades ago using arbitrary methods of grading tumor response that were never intended to be used for clinical significant outcomes.
The researchers suggest that improvements in the drug development process should start by using efficacy grading techniques that were intended for clinical outcomes, and are reflective of current capabilities in medical imaging. The recommendation that they make involve using pathological complete response (pCR), which takes into account the effects that drugs have on metastatic cancer cells rather than just the impact on solid tumor tissue cells. This method is currently used for neoadjuvant trials, and could be used to predict improvements in overall survival for novel drug compounds. In a review of numerous clinical studies the authors found usage of pCR methods in neoadjuvant methods to determine efficacy correlated to improved survival outcomes in breast cancer, muscle-invasive bladder cancer, and Non-small cell lung cancer.
The FDA has already approved pCR as a relevant indicator of neoadjuvant efficacy and as a surrogate indicator of increased survival in some breast cancer patients. However, it is possible that this modern means of assessing cancer response could lead to an increase in the approval of new cancer drugs based on better ability to measure cancer response in patients. The question that remains is: does this new method of efficacy evaluation seem like it will increase options for oncologists to improve survival rates, or is it possible that it will lower standards of approval to the detriment of cancer patients?
Funt, S. A., & Chapman, P. B. (2016). The Role of Neoadjuvant Trials in Drug Development for Solid Tumors. Clinl Cancer Res. 2016; Published OnlineFirst February 3, 2016; doi: 10.1158/1078-0432.CCR-15-196.