Three Questions with NiP Project Team Members
January 25, 2021 — The FNIH Biomarkers Consortium “A Novel Total Lesional Automated Computerized Imaging Platform, Biomarker, and Predictive Model for Metastatic Prostate Cancer Project (NiP- Metastatic Prostate Cancer) is an off-shoot of the FNIH Biomarkers Consortium Vol-PACT project that closed December 2020. The NiP – Metastatic Prostate Cancer Project is a three-year effort that launched in November 2020.
The project team members describe what led to this project and the benefits it presents for men at risk of or diagnosed with a specific type of prostate cancer (mCRPC).
Three Questions with NiP Project Team Members
Michael Morris, M.D., Clinical Director, Genitourinary Medical Oncology Service and Prostate Cancer Section Head, Division of Solid Tumor Oncology at Memorial Sloan-Kettering Cancer Center.
Lawrence Schwartz, M.D., James Picker Professor and Chairman for the Department of Radiology at Columbia University Medical Center.
Gary Borzillo, Ph.D., Scientific Director at Janssen Research & Development, LLC.
1. What is the major need that led to this initiative?
This type of prostate cancer, metastatic castration-resistant prostate cancer or mCRPC, is the second leading cause of cancer death for American men. Despite ongoing efforts to develop better endpoints for prostate cancer clinical trials and some resulting success, there remain challenges posed by the current endpoints in use, which involve the use of a bone scan and reliance on subjective human interpretation. The imaging platform put forth by our team will allow for more objective outcome assessments of clinical trials, more streamlined clinical trials and resulting data interpretation, and faster identification of treatments for men with this lethal form of prostate cancer.
The technology would represent the first automated tool to fully and quantitatively assess tumor burden for response assessment in prostate cancer. It is also the first predictive model in prostate cancer to incorporate imaging.
For radiologists, this will mean more efficient and accurate interpretation. For doctors, patients and researchers, it means early identification and a better way to see which active therapies should be continued and which ineffective ones discontinued.
2. How did the FNIH Biomarkers Consortium project Vol-PACT (Volumetric CT for Precision Analysis of Clinical Trial Results) spur the launch of this effort?
Vol-PACT Phase II is a three-year FNIH research partnership, which was designed to develop new methods for analyzing digital images to accurately measure cancer response and progression. Through that project we were able to aggregate imaging data from multiple completed, pharmaceutical industry-sponsored, phase II and III clinical trials in colorectal cancer, renal cell carcinoma, non-small cell lung cancer and melanoma, and have been evaluating the characteristics of cancer progression to generate better criteria for progression compared to Response Evaluation Criteria in Solid Tumors (RECIST), which is the current image analysis standards used for targeted and immuno- therapies in solid tumors.
As we were developing the Vol-PACT project there was great interest from both industry and the team to evaluate tumor progression in Prostate cancer as well. Given that prostate tumors generally metastasize to bone, the criteria used for their measurement and evaluation are quite different from RECIST however. These criteria, known as the Prostate Cancer Working Group 3 (PCWG3) criteria, provide a time-to-event progression endpoint for bone scan interpretation instead. Members of the NIP project team helped to validate them, and they ultimately served as the basis for a regulatory drug approval, but there is still a great unmet need for superior endpoints, which the NiP Project Team seeks to address.
3. What overall benefits could this project present for men at risk of or diagnosed with this particular type of prostate cancer (mCRPC)?
For patients with mCRPC, the limited tools to indicate a clinically meaningful response to or progression on therapy has significantly impeded drug development and clinical care. Patients have access to multiple life-prolonging treatments that, when given after a new drug is being tested in a clinical trial, can significantly obscure the activity of the study drug. These treatments can prevent the identification of active drugs. In order to continue identifying successful therapies for lethal prostate cancer, we must develop new biomarkers that can deliver a readout of a drug’s activity earlier than OS, without the contamination of post-protocol treatment effects. Such biomarkers would not only accelerate the identification and development of promising new therapeutics, they could be used by physicians to assess treatment effects in individual patients as well.
This project presents an opportunity for more reproducible and accurate interpretation of patients’ full disease burden, with less inter-reader variability and error and for active monitoring of disease. This project offers both patients and physicians a potential new tool that will enable early identification and monitoring of active therapy that should be continued and ineffective treatments that should be abandoned.