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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.

Prostate Cancer Treatment: Getting the Best Results by Targeting the Right Cells at the Right Time

Lutetium 177 (also known as Lu-177 or 177-Lu) is a very popular radioactive particle used to treat prostate cancer in Europe, as it has previously been shown to be effective against metastatic prostate cancer. For more than 10 years, Weill Cornell Medicine has been one of very few centers in the United States that is able to offer this as a targeted prostate cancer treatment.

Lutetium 177 is a radioactive material that has a short-range, which means that it can act in a targeted fashion against cancer cells with little “collateral” damage to nearby organs and tissues. It needs some help to get to these specific cancer cells though, so we combine it with the J591 monoclonal antibody that binds to a protein expressed on nearly all prostate cancer cells, PSMA. Together, this treatment compound is called 177Lu-J591.

Here’s an overview of how we use monoclonal antibodies to target cancer cells, in this case the target is the prostate cancer tumors:

The treatment approach is called radioimmunotherapy because we’re using a tiny tag of radioactive material that can kill prostate cancer cells (in this case 177Lu) and attaching it to a very specific immune-based courier (J591) to help it get inside these cells.

We already know that 177Lu-J591 can be very effective at eradicating metastatic prostate cancer cells throughout the body. In 2013, we published results from a phase II clinical trial showing that a large, single-dose of this radioimmunotherapy could be safely delivered to patients and that those patients receiving a larger dose had better response and overall survival. This is what’s called a “dose-response.”

While higher doses of 177Lu-J591 are more effective at eradicating the prostate cancer cells, higher doses also increase the likelihood of side effects, including drops in the white blood cell and platelet counts in the blood.

Building on the results of this trial and additional scientific evidence, we hypothesized that by splitting the radiation dose and giving half at the first visit and half two weeks later (a process termed “dose fractionation”) that we would be able to deliver a higher dose of the treatment while minimizing the risk of these side effects.

Scott Tagawa_ASCO2016 — *Dr. Tagawa presents the clinical trial results at ASCO 2016 in Chicago*

Today at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, Dr. Scott Tagawa presented final results utilizing this split-dosed approach.

The clinical trial showed that the most effective split-dose of 177Lu-J591 was 45 mCi/m² given in two sessions, two weeks apart, a dose 28% higher than was achievable with a large single-dose. Nearly 90% of the patients in this group experienced a decline in PSA levels, resulting in an average overall survival of more than four years. In addition, the number of circulating tumor cells (also known as CTCs or prostate cancer cells floating in the blood) was decreased or controlled by treatment. In addition to this study, the lower effect of fractionated therapy on blood counts has allowed combination of this therapy with chemotherapy.

This research was supported by the Department of Defense, Prostate Cancer Foundation and the National Institutes of Health.

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