September 14 2020
Parallel Phase III Randomized Trials for High Risk Prostate Cancer Evaluating De-Intensification for Lower Genomic Risk and Intensification of Concurrent Therapy for Higher Genomic Risk With Radiation (PREDICT-RT*)By Paul Nguyen, MD, of the Dana-Farber Cancer Institute and Principal Investigator of NRG-GU009 and Oliver Sartor, MD, of Tulane Cancer Center and Co-Principal Investigator of NRG-GU009High risk localized prostate cancer has been treated traditionally with either radical prostatectomy or a combination of androgen deprivation therapy (ADT) plus radiation. NRG has traditionally enrolled well in the high risk prostate cancer space and prior trials have help to define the standard of care which consist of radiation to the prostate +/- regional nodes and 18-36 months of ADT.
One key question that arises, is whether or not the "one size fits all" approach provides optimal treatment given the known heterogeneity of these cancers. It is likely that some patients are over treated by standard regimens and other patients will be under treated. Over treatment leads to unnecessary side effects and under treatment can yield excessively high relapse rates.
One significant advance, fueled in part by leaders such as Drs. Felix Feng and Paul Nguyen, is genomic risk stratification. By using transcriptomic expression data, additional knowledge is gained providing important prognostic information on top of traditional classifiers that use PSA, Gleason scores, and stage.
In a new protocol (PREDICT-RT or GU009), patients traditionally classified as high risk prostate cancer, with no distant metastases, will have a transcriptomic (Decipher) risk classification and be divided into two groups depending on whether or not their Decipher scores are high risk or low/intermediate risk. Those in the low risk category will be randomized to receive either standard of care (radiation + 24 months of ADT) or radiation + 12 months of ADT deprivation therapy. This "de-intensification" arm of the phase 3 trial well assess metastasis free survival using a non-inferiority statistical design.
The" intensification arm" is reserved for those with higher Decipher scores (>0.8) and those with pelvic lymph nodes (TxN1M0). This group will randomly receive standard therapy (radiotion therapy + 24 months of standard ADT) or radiation therapy + ADT + abiraterone/prednisone + apalutamide. For those in the intensification component of the study there will be a "superiority' statistical design looking at metastasis free survival. For both the intensification and the intensification arm there will be a variety of secondary endpoints including overall survival, time to PSA failure, etc.
This will be the first large phase 3 prostate cancer trial using a genomic risk stratifier and results may alter the current standard of care. GU009 (PREDICT-RT) will be opening soon and we anticipate robust accrual in both arms.