Maha Hussain, MD, FACP, FASCO, Genevieve E. Teuton Professor of Medicine in the Division of Hematology and Oncology of the Department of Medicine, and the deputy director of the Robert H. Lurie Comprehensive Cancer Center of the Northwestern University Feinberg School of Medicine, discusses the importance of meaningful effect in prostate cancer trials.

Effective treatments are important and metrics to judge effectiveness cannot be limited to a lab value, says Hussain. Achieving a meaningful effect entails delaying the time to cancer spread, enhancing the response rate, and prolonging life, which Hussain emphasizes is the ultimate goal. Using what was discovered in the phase 3 PROSPER study, this is something that has been shown in advanced cancer and has been applied to nonmetastatic castration-resistant prostate cancer. The results provide a good indication of the potential benefit presented to an individual patient. This will hopefully help with guiding therapy for the patient, as well as disease management in terms of imaging and other interventions, Hussain says.

From a research perspective, these types of intermediate end points are important, Hussain explains. To do a large study and empower it for overall survival or metastasis-free survival is expensive, comprises thousands of patients, and can take many years. If multiple ideas are being developed in this setting, such as combination treatments or developing a new agent, looking at meaningful effect as an intermediate end point and an early metric will help to determine whether the treatment is effective. At the end of the day, definitive trials must be done; however, this allows for a shortcut to pick the right therapy, concludes Hussain.

Videos

Maha Hussain, MD, FACP, FASCO, discusses the importance of meaningful effect in prostate cancer trials.

Dr. Hussain on Meaningful Effect as an End Point in Prostate Cancer Trials

Maha Hussain, MD, FACP, FASCO, Genevieve E. Teuton Professor of Medicine in the Division of Hematology and Oncology of the Department of Medicine, and the deputy director of the Robert H. Lurie Comprehensive Cancer Center of the Northwestern University Feinberg School of Medicine, discusses the design of the phase 3 PROSPER trial in patients with nonmetastatic castration-resistant prostate cancer (CRPC).

Updated results from the PROSPER trial were presented during the 

, says Hussain. In the phase 3 trial, patients with nonmetastatic CRPC were randomized 2:1 to receive either enzalutamide (Xtandi) or placebo. At the time of disease progression, patients were unblinded and permitted to receive alternative treatments, according to Hussain.

The updated data focused on whether benefit with enzalutamide can be predicted at an individual patient level, Hussain adds. When clinical trials are conducted, they’re done in groups of patients; however, each and every patient case is distinct. One cannot assume that if 1patient experienced benefit with a treatment that another patient will also experience benefit, notes Hussain. Additionally, it is important to be mindful of how frequently patients will be subjected to imaging because of the associated physical and monetary costs.

This research builds on data from another phase 3 clinical trial that examined the nadir prostate-specific antigen (PSA) and its association with outcomes in terms of overall survival and metastasis-free survival. In the context of metastatic disease, it was demonstrated that a decreased and maintained PSA at a certain low level can predict for better outcomes, adds Hussain. When a tumor responds, that is better than a tumor that is not responding. Essentially, a similar trend was demonstrated in PROSPER, concludes Hussain.

Maha Hussain, MD, FACP, FASCO, discusses the design of the phase 3 PROSPER trial in patients with nonmetastatic castration-resistant prostate cancer.

Dr. Hussain on Rationale to Explore Relationship Between PSA and Outcomes in Nonmetastatic CRPC

Maha Hussain, MD, FACP, FASCO, Genevieve E. Teuton Professor of Medicine in the Division of Hematology and Oncology, Department of Medicine, and Deputy Director at the Robert H. Lurie Comprehensive Cancer Center, of Northwestern University Feinberg School of Medicine, discusses the implications of the phase III PROfound trial in metastatic castration-resistant prostate cancer (mCRPC).

Findings from the phase III PROfound trial demonstrated that olaparib (Lynparza) improved radiographic progression-free survival (rPFS) versus physician's choice of abiraterone acetate (Zytiga) or enzalutamide (Xtandi) in men with heavily pretreated mCRPC and homologous recombination repair (HRR) gene alterations.

These data, in addition to establishing a new treatment options for patients, provide a robust demonstration of the potential for precision medicine in the field, concludes Hussain.

Dr. Hussain on the Implications of the PROfound Trial in mCRPC

Maha Hussain, MD, FACP, FASCO, Genevieve Teuton Professor of Medicine in the Division of Hematology and Oncology, Department of Medicine, and Deputy Director at the Robert H. Lurie Comprehensive Cancer Center, of Northwestern University Feinberg School of Medicine, discusses the results of the phase III PROfound trial in metastatic castration-resistant prostate cancer (mCRPC).

Data presented at the 2019 ESMO Congress demonstrated that olaparib (Lynparza) improved radiographic progression-free survival (rPFS) versus physician's choice of abiraterone acetate (Zytiga) or enzalutamide (Xtandi) in men with heavily pretreated mCRPC and homologous recombination repair (HRR) gene alterations.

In the trial, investigators reported a median rPFS of 7.39 months in patients with 

 alterations (cohort A) treated with olaparib versus 3.55 months in those treated with hormone therapy (HR, 0.34; 95% CI, 0.25-0.47; 

 <.0001). Importantly, the time to pain progression was significantly delayed with olaparib versus hormone therapy, says Hussain. A trend toward improved overall survival was also noted in the olaparib arm, but further follow-up is needed to make a definitive assessment, she concludes.

Maha Hussain, MD, FACP, FASCO, Genevieve E. Teuton Professor of Medicine in the Division of Hematology and Oncology, Feinberg School of Medicine, and Deputy Director at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, discusses the results of the phase III PROfound trial in metastatic castration-resistant prostate cancer (mCRPC).

Dr. Hussain on Results of the PROfound Trial in mCRPC

Maha Hussain, MD, FACP, FASCO, Genevieve E. Teuton Professor of Medicine in the Division of Hematology and Oncology, Feinberg School of Medicine, and Deputy Director at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Dr Hussain has been a leading oncologist in the genitourinary cancer field, and is focused on the development of novel therapeutics integrating scientific advances into clinical trials in prostate and bladder cancer.

Thus far, she has had an impressive career in oncology, including her contribution to research that led to the FDA approval of docetaxel for the treatment of men with advanced prostate cancer. As a lead investigator in an international collaborative trial, she also evaluated optimal schedules of androgen deprivation therapy for patients with newly diagnosted metastatic prostate cancer.

 recognized Dr Hussain as a Giant of Cancer Care

In our exclusive interview, Dr. Hussain reflected on the path that led her into GU cancers, pivotal research she has been a part of and strategies in the pipeline she is intrigued by, and the challenges she has overcome in her career while offering advice to young oncologists just getting started in the field.

Podcasts

Maha Hussain, MD, FACP, FASCO, reflects on the path that led her into genitourinary cancers, and the challenges she has overcome in her career while offering advice to young oncologists just getting started in the field.

Maha Hussain, MD: Anything Is Possible With a Fire in the Belly

Maha Hussain, MD, FACP, FASCO, Genevieve Teuton Professor of Medicine, Deputy Director, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, discusses PARP inhibitors in the treatment of patients with prostate cancer.

The interest in PARP inhibitors began with early observation that the use of targeting DNA repair may be of benefit in the treatment of patients with prostate cancer. From there, a clinical trial that hypothesized that co-targeted androgen receptor (AR) and DNA repair with the use of a PARP inhibitor is a relevant strategy, and the combination will have a better outcome than targeting AR alone. This combination may be of particular benefit for a certain subset of patients with prostate cancer who have S-gene fusions, Hussian says.

In a recent clinical trial sponsored by the National Cancer Institute, patients with metastatic castration-resistant prostate cancer underwent a metastatic disease biopsy for an evaluation of their ETS tumor status. They were then stratified by ETS status and randomized to abiraterone acetate (Zytiga) plus prednisone, or abiraterone plus prednisone and the PARP inhibitor veliparib.

Maha Hussain, MD, FACP, FASCO, Genevieve Teuton Professor of Medicine, Deputy Director, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, discusses PARP inhibitors in the treatment of patients with prostate cancer.
 

Maha Hussain, MD, FACP, FASCO

Articles

Dr. Hussain on Meaningful Effect as an End Point in Prostate Cancer Trials

Dr. Hussain on Rationale to Explore Relationship Between PSA and Outcomes in Nonmetastatic CRPC

Dr. Hussain on the Implications of the PROfound Trial in mCRPC

Dr. Hussain on Results of the PROfound Trial in mCRPC

Maha Hussain, MD: Anything Is Possible With a Fire in the Belly

Dr. Hussain Discusses PARP Inhibitors in Prostate Cancer