ASCO 2016: Updates in Advanced Prostate Cancer and Precision Medicine

Advances in therapeutics have led to improvements in both survival and quality of life for patients with cancer, including men with advanced prostate cancer. Simultaneously, a number of cutting-edge scientific advances have been made in the underlying biology of advanced prostate cancer. There is great potential and power in integrating these new therapeutics and biomarkers, which is often referred to precision medicine. While great advances have already been made in this area, many remain highly sophisticated and restricted to selected centers, such as Weill Cornell Medicine and NewYork-Presbyterian Hospital, while others still need validation in a larger number of patients. Ultimately, the goal is to be able to bring these technologies and treatments to cancer patients all around the country and the world.

MishaBeltran_ASCO16
Dr. Misha Beltran speaks to a full house at the ASCO 2016 Annual Meeting in Chicago.

At the 2016 ASCO meeting, Dr. Himisha Beltran was the chair of a session entitled “Precision Medicine in Advanced Prostate Cancer: Understanding Genomics, Androgen Receptor Splice Variants, and Imaging Biomarkers.” This session intended to demystify some of the language and updates surrounding precision medicine.

Dr. Beltran spoke about important recent advances in tumor and patient genomics, such as the specific genetic alterations that we now know drive different types of tumors and play a role in the development of aggressive forms of the disease. The Cancer Genome Atlas (TCGA), a government-led initiative through the National Cancer Institute (NCI) has generated multi-dimensional maps for key genomic changes in 33 different types of cancer. It also provides a collaborative platform for physicians and researchers to search, download, and analyze data. Through the TCGA there have been critical discoveries regarding untreated primary prostate tumors with molecular classification of different subtypes that go beyond Gleason scores (the common way pathologists “grade” the aggressiveness of tumors).

Additionally, the first publication of the Stand Up to Cancer Prostate Cancer Dream Team demonstrated the genomic landscape of metastatic biopsies in the castration-resistant setting, which have differences compared to primary prostate tumors and fall into groups which may be targetable by certain therapies. Dr. Mark Rubin is the Weill Cornell Primary Investigator for the Stand Up to Cancer Dream Team. In addition, as follow up to Dr. Beltran’s initial 2011 publication, she detailed the results of Weill Cornell’s collaborative efforts leading to key discoveries in neuroendocrine and castration-resistant prostate cancer using tumor tissue as well as circulating tumor cell analysis.

Collaborator Dr. Gerhardt Attard presented data on utilizing DNA obtained from blood only, an emerging method of accessing the tumor’s genomic information in a non-invasive manner, which may decrease the need for a biopsy and allow for multiple samples to be assessed over time. One clinically relevant portion of his work, being done in collaboration with Drs. Beltran and Francesca DeMichelis, is ongoing through a Prostate Cancer Foundation – Movember Challenge Award grant. Together, we are leveraging our published genomic data on neuroendocrine and treatment-resistant prostate cancer with the circulating tumor DNA from blood technology to assess patients’ cancer status before, during, and after treatment.

In addition to improvements in tumor and blood-based biomarkers, imaging biomarkers are also being investigated. Dr. Michael Morris described standardizing the use of traditional scans to assess prostate cancer progression. In addition, there are a number of molecular imaging modalities that may demonstrate increased sensitivity in the detection of tumors as well as give insight into the biology of individual tumors, highlighted by prostate specific membrane imaging including the New York-based collaboration between Memorial Sloane Kettering Cancer Center and Weill Cornell Medicine investigators.

ASCO 2016 is Upon Us

Each year, more than 30,000 professionals from around the world come together to discuss groundbreaking research findings at the American Society for Clinical Oncology (ASCO) annual meeting.

This year’s meeting, in Chicago from June 3-7, will feature over 5,000 different abstracts. The Genitourinary (GU) Oncology team will be presenting recent prostate and kidney cancer clinical trial results and updates on using precision medicine to translate genomic information into treatments. Vice President Joe Biden will also be at ASCO to deliver remarks on the Cancer Moonshot Initiative to accelerate cancer research and improve patient care through increased collaboration.

Check out the schedule to see when we’ll be presenting, and be on the lookout for daily “What’s New in GU?” blog updates regarding these noteworthy topics and more:

  • The impact of a split-dose schedule using Lutetium 177, a targeted treatment that has been previously shown to be effective against metastatic prostate cancer
  • The effect of changing prostate cancer chemotherapies early on when one drug doesn’t seem to be working as effectively as it could be, and when to switch
  • How a blood test may be used to detect trace tumor cells in the body and what this reveals about the mechanism behind taxane chemotherapy treatment

ASCO 2016

Chemo and Prostate Cancer: Not All Treatments (or Cancers) are Created Equal

By Scott Tagawa, M.D.

In casual conversations, chemotherapy is often referred to as one type of cancer treatment, but it actually refers to different classes of drugs/medications that work via a similar mechanism.

Taxanes are the only class of cheTagawa_Prostate Cancer_Chemotherapymotherapy agents that have significantly improved survival in men with advanced prostate cancer. These include docetaxel (Taxotere ®) and cabazitaxel (Jevtana ®). Though there have been exciting advances in hormonal therapies, bone-targeted therapies, and immunotherapies that have led to a multitude of FDA-approved therapies for patients, chemotherapy is a mainstay.

Chemotherapy was initially approved because men with advanced prostate cancer felt better and in less pain after receiving it. In 2004, docetaxel chemotherapy was approved because it made men feel even better than the older chemotherapy and it also controlled the prostate cancer well enough to lead to longer lifespan. However, the use of chemotherapy was initially limited due to fears of side effects and since 2011, additional medicines have been approved.

The recent success in large clinical trials using taxane chemotherapy has demonstrated unprecedented survival advantages when these drugs are used early. The CHAARTED and STAMPEDE trials showed a much larger improvement in survival compared to any treatment that has been studied in the modern era. Additional trials of men with earlier stages of prostate cancer have also pointed towards patient benefit. However, not all men respond to this treatment and despite improvements in quality of life for symptomatic men with advanced cancer, side-effects do exist. As a result, there is interest in identifying markers that can more accurately identify patients who will respond to this treatment and those for whom taxane chemotherapy is less likely to work. Many efforts are already in the works and progress has already been made.

A genetic alteration known as TMPRSS2-ERG that was co-discovered by Weill Cornell Medicine (WCM)’s Dr. Mark Rubin, Director of the Caryl and Israel Englander Institute for Precision Medicine, is unique to prostate cancer and present in tumors in about 50% of men with prostate cancer. Interestingly, we later discovered that the protein created by this gene fusion called ERG binds to tubulin, which is the molecular target of taxane chemotherapy.

Because of this protein’s interaction with tubulin, there is interference with the “drug-target engagement” of taxanes, leading to resistance. With this scientific discovery, in addition to outlining the mechanism and demonstrating drug-resistance in lab experiments, WCM investigators in collaboration with a group in Sydney tested tumors from human patients that received docetaxel chemotherapy. In this small group of men, those whose tumors expressed ERG were less likely to respond to docetaxel.

In a recent publication, Spanish investigators built on this discovery and identified TMPRSS2-ERG as a biomarker present in the bloodstream, making it a potentially easy way to use a blood test to predict resistance to taxane chemotherapy. This group of scientists from Barcelona used a blood test in men with advanced prostate cancer prior to starting docetaxel or cabazitaxel chemotherapy to determine the presence of TMPRSS2-ERG. Their work confirmed that men with tumors harbouring the gene fusion have resistance to this type of chemotherapy.

Though additional research is ongoing (and needed), there are now a number of treatment choices available. In the near future, physicians might be able to pick the drug that is most likely to work on an individualized basis, perhaps even through a simple blood test. This is another step towards our goal of precision medicine: the right treatment for the right patient at the right time.