BERKELEY, CA (UroToday.com) - Neoadjuvant treatments prior to radical prostatectomy have thus far not demonstrated overall survival benefits in prostate cancer. The reasons for this are complex, and factors including trial design, patient selection criteria, biological differences between locally advanced and metastatic disease, and drug efficacy, have been implicated as contributory. Rather than discouraging us from neoadjuvant treatment, we can learn from these earlier trials to re-design neoadjuvant approaches to take advantage of advances in our understanding of cancer biology, genomic profiling, functional proteomics, and imaging technologies. Developing biologically relevant intermediate endpoints and validating their correlation to clinical outcomes will be a key component of this future work. This will facilitate rational matching of new treatments to those individuals most likely to benefit from them, streamline the clinical trials process, and increase the success rates of developing clinically active new drugs and drug combinations.
Indeed, the potential usefulness of modifying the neoadjuvant platform is being explored in the I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis 2) for women with locally advanced breast cancers who qualify for preoperative chemotherapy (ClinicalTrials.gov identifier: NCT01042379).[1, 2] In this trial, individuals are assigned to standard preoperative chemotherapy, with or without the addition of one of 12 experimental agents, depending upon their tumor characteristics. This innovative approach intends to inform us of which investigational agents are most beneficial to each group of women with biologically distinct breast tumors. Applying the principles and rationale behind the I-SPY 2 TRIAL to high-risk prostate cancer may similarly result in highly informative trials, and expedite development of neoadjuvant treatments for prostate cancer. Importantly, by bringing the most active and promising new treatments into the earlier stages of disease where the potential for cure is highest, it serves to increase our ability as clinicians to provide meaningful and long-term disease control for men with high-risk prostate cancer.
- Printz C. I-SPY 2 May Change How Clinical Trials Are Conducted. Cancer 2013 Jun 1;119(11):1925-7. doi: 10.1002/cncr.28172
- Rugo HS, Olopade O, DeMichele A, van 't Veer L, Buxton M, Hylton N, Yee D, et al. Veliparib/carboplatin plus standard neoadjuvant therapy for high-risk breast cancer: First efficacy results from the I-SPY 2 TRIAL. San Antonio Breast Cancer Symposium 2013. Abstract.
David Y. Lou, MD, PhD and Lawrence Fong, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Division of Hematology/Oncology, University of California, San Francisco, CA; UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA USA