ASCO 2017: Interpreting Biomarkers and Trial Outcomes: How Confident Are We?
In the first abstract (5006) Dr. Armstrong presented results of a phase 3 prognostic analysis of the automated bone scan index (aBSI) in men with bone metastatic castration resistant prostate cancer (mCRPC). The majority of mCRPC men have bone metastasis. 40-50% of these patients are expected to have flare with androgen receptor targeted therapies, such as Abiraterone and Enzalutamide. Therefore, it is important to have a tool to classify patients as true progression. The Prostate cancer working group 3 defines bone scan progression metrics but remains semi-quantitative. Dr. Armstrong showed that aBSI was associated with overall survival. Dr. Halabi summarized this abstract by stating the strengths of aBSI, including its high accuracy in detecting and classifying bone lesions, the fact that it is automated leading to a significant reduction in time and variability among readers, and its ability to predict overall survival (OS), and clinical outcomes. Despite its many advantages, Dr. Halabi concluded her summary of this abstract with an open question of whether the aBSI reflects tangible clinical benefit.
The next summarized abstract (5007) focused on whether circulating tumor cells (CTCs) will be useful for the longitudinal assessment of tumor biology in men with mCRPC undergoing relevant systemic therapy. Dr. Heller presented this study including 5192 men from five major randomized clinical trials, assessing CTC as a response endpoint and contrasting it with PSA. According to Dr. Halabi, the strengths of this study is the fact that baseline CTC is a known prognostic factor of OS, and the fact that the results showed that CTC conversion was associated with OS. Major limitations of this study included its high cost, not being evaluable in all patients, and the fact that reducing CTCs is challenging. In summary, this study demonstrated that CTC0 and CTC conversion were found to have had higher weighted c-indices than PSA response. Therefore, in evaluable patients with CTC, CTC0 and CTC conversion may be useful as an intermediate endpoint for go/no go decision in phase 2 clinical trials.
Dr. Halabi ended her presentation with a summary of Dr. Nabid’s study (Abstract 5008) comparing 18 months with 36 months of androgen deprivation treatment (ADT) with radiotherapy for localized high risk prostate cancer patients. In short, Dr. Nabid’s study showed similar oncologic outcomes and better quality of life outcomes in the shorter ADT arm of his study, with no difference in OS or disease free survival. However the patients on the shorter treatment arm had higher hazard of biochemical failure compared to the patients on the longer treatment arm. Lastly, Dr. Halabi emphasized the statistical aspect of this study, stating that although it may seem reasonable to conclude that the 18 months of ADT is similar to 36 months of ADT, in fact a non-significant test result from a superiority comparison cannot be used to establish ‘similarity’. Therefore, optimal duration of ADT plus radiotherapy for localized high risk prostate cancer patients is still not known.
Presented By: Susan Halabi, PhD, Duke Cancer Institute
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre
Twitter: @GoldbergHanan
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA