2017 Genitourinary Cancers Symposium

gu_symposium_2017_img_3054The 2017 Genitourinary (GU) Cancer Symposium kicked off on February 16th in Orlando, Florida, bringing together more than 3,000 attendees from all over the world. At this annual conference, clinicians from a wide range of disciplines treating people with prostate cancer, kidney cancer, bladder cancer, and testicular cancer come together to hear from experts on the latest scientific discoveries and how they impact clinical care for patients.

The Weill Cornell Medicine (WCM) and NewYork-Presbyterian (NYP) GU Oncology team is down in the Sunshine State highlighting the cutting-edge research and patient care that has been taking place back on campus in New York City.

twitter-iconTeam member Dr. Bishoy Faltas was selected by the conference to be a “Featured Voice” on Twitter, so be sure to follow him (@DrFaltas) for updates in real-time. Dr. Scott Tagawa (@DrScottTagawa) is now on Twitter too and also tweeting live from the symposium. The official conference hashtag is #GU17.

Some #GU17 highlights

Day 1 – The initial session focused on active surveillance for prostate cancer, including using both imaging as well as tissue biomarkers to help select optimal patients for surveillance versus those who should undergo surgery or radiation. A subsequent session focused on prostate cancer that progresses despite therapy and the pathways of resistance that can develop. This included a discussion of prostate cancer subtypes that become independent of the androgen-receptor (hormonal) pathway, including aggressive variant and neuroendocrine prostate cancer (NEPC). Neuroendocrine prostate cancer is one of the most aggressive and treatment-resistant types of prostate cancer that most often evolves from prior hormonal therapy.

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Dr. Misha Beltran and Dr. Gerhardt Attard are two of the primary investigators for the 2016-2018 Movember Foundation-PCF Challenge Award

Dr. Gerhardt Attard at the Institute of Cancer Research in London, gave a great talk on the value of circulating tumor DNA in prostate cancer. He spoke about the collaborative grant from the Movember Foundation and the Prostate Cancer Foundation (PCF) that he, Dr. Misha Beltran and others have used to develop signature ways to confirm neuroendocrine prostate cancer with a blood test. An additional collaborative grant will allow optimization of this technology across a larger number of centers. Learn more about this prestigious Movember Foundation-PCF Challenge Award and how we’re using genomic characterization of tumors in less invasive ways in order to bring precision medicine – or narrowly tailored, personalized treatment – to more patients.

evi_taxynergy_gu-symposium_jpgDr. Evi Giannakakou explains to a crowd of physician-scientists results from our TAXYNERGY clinical trial showing additional evidence of using cancer cells circulating in the blood, also referred to as circulating tumor cells or CTCs, as a primary biomarker for chemotherapy response. This research validated prior work regarding the mechanism of action of chemotherapy in prostate cancer and demonstrates that using a simple blood draw, within one week of first chemotherapy treatment, we’re able to determine whether men with metastatic prostate cancer have a higher chance of responding. In the future, this might spare men from additional treatment (with associated side effects) with a drug that has a lower chance of working. For additional background information on this research, check out our prior in-depth blog post on the topic.

jok9106Dr. Josephine Kang, a radiation oncologist at WCM/NYP, presented a poster on Stereotactic Body Radiotherapy (SBRT), which is an emerging treatment modality with excellent control rates for low- and intermediate-risk prostate cancer. The role of SBRT for high-risk prostate cancer has not been studied as closely, but this trial showed encouraging results for those with high-risk disease. These results are very encouraging, as the treatment can be completed in 5 treatments. Additionally, this data longitudinally followed men treated with this modality for 7 years, and it appears to be a safe and effective treatment for high-risk prostate carcinoma. SBRT may be a good treatment alternative particularly for patients unable to undergo hormonal therapy (androgen receptor therapy/ADT) or unwilling to receive standard 8-9 week radiation therapy. More research is ongoing. Learn more about our open clinical trial using this modality. Another study will soon be opening.

In the oral abstract session, data was presented from a cooperative group trial that the older chemotherapy drug mitoxantrone should not be used immediately following surgery. Assays from biopsy material can separate different classes of prostate cancer with different risk for inferior outcomes. Blood biomarkers utilizing circulating tumor cells appear to be prognostic and potentially predictive of response to certain drugs. We are currently participating in a study to validate this data across multiple institutions and technology platforms.

In the keynote lecture, Dr. Charles Drake who recently joined the NYP family at Columbia discussed the current status and future directions of immunotherapy for prostate cancer.

Stay tuned for additional updates throughout the symposium!

Lutetium 177 Radioimmunotherapy Clinical Trial Open for Men with Rising PSA Levels

We have an open clinical trial using radioimmunotherapy for men who have been diagnosed with prostate cancer, and whose PSAs are rising despite initial hormonal therapy but have no evidence of metastatic disease on scans (no tumors seen on CT/MRI and bone scan). This clinical trial is investigating whether attaching Lutetium 177 with the monoclonal antibody J591 (177Lu-J591) can delay or prevent the disease progression to overt metastatic disease in men with “biochemical progression”.

J591 can recognize a protein antigen known as PSMA (also known as anti-prostate-specific membrane antigen) that is present on the surface of nearly all prostate cancer tumors and circulating tumor cells.

The targeted treatment in this trial uses J591 as a delivery vehicle for the radioactive treatment (Lutetium 177) to be delivered directly to the prostate cancer cells that may be hiding or circulating in the body (for example in lymph nodes, the blood stream or the bones).

The Lutetium 177-J591 treatment approach may be ideal for men who are experiencing rising PSA levels after primary prostate cancer treatment and early hormonal therapy, but whose bone and CT scans remain negative. Even though we can’t detect the presence of cancer on these traditional imaging scans, we know from prior research that these men have what we call “micro-metastatic” disease, meaning that the prostate cancer cells are increasing throughout the body because otherwise PSA levels would not be so high or increasing at such a rapid rate. Unfortunately, even with traditional hormonal manipulation, metastases become evident in these men after months. Although we have treated many men with overt metastatic prostate cancer and demonstrated anti-tumor responses, we have also shown that we are able to target these micro-metastatic sites (tumors that are too small to be seen on CT or bone scan), and the properties of 177-Lu make it more optimal for tumors that are too small to be seen on conventional imaging.

Many patients fall in this category in a broad sense and usually these men feel completely fine. Approximately 50,000 new men per year in the U.S. suffer a biochemical relapse (rising PSA after surgery or radiation) and some of these men will have further PSA rises despite the most common type or hormonal therapy, which are injections to bring down testosterone levels. The goal is to intervene earlier on in order to bring more men to cure and suppress the disease from further progression and metastases.

Men in this phase II study will be randomized and all patients will receive oral hormonal therapy as part of treatment which also serves to boost their PSMA level (i.e. increase the number of “locks” per tumor cell). Since PSMA is the target for 177Lu-J591, radioimmunotherapy increased expression of PSMA can lead to more targeting of the otherwise invisible tumor cells. Two-thirds of patients will receive 177Lu-J591 at the highest tolerated dose that improved outcomes based on our prior study and the remaining one-third will get J591 with a diagnostic isotope (111Indium). The isotope 111-Indium (abbreviated 111In) is also an energetic radioactive particle, but it does not generally give off enough energy to kill cancer cells while still allowing researchers to take more detailed pictures of where the prostate cancer is located in the body.

Our goal is to ultimately cure the men who fall in this category by eradicating microscopic deposits of cancer, and the Weill Cornell Genitourinary Oncology team is available for patient consultations and to speak with physicians who are interested in referring patients to this trial, which is available at a number of sites across the country.

Learn more about how this treatment works in this article and video:

Promising New Radioligand Treatment for Men with Metastatic Prostate Cancer Using Lutetium 177 (177Lu)

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Using small molecules, we are able to target not only the known tumors, but can also treat the unknown tumors.

Physicians and researchers at Weill Cornell Medicine have been utilizing prostate specific membrane antigen (PSMA)-directed radioisotope therapy for more than a decade. Over the years, we have shown that we could use this approach to target the vast majority of prostate cancer tumors (“hitting” essentially all known tumors and avoiding normal organs), demonstrated anti-tumor responses when the J591 antibody is linked to a radioactive particle with a large (single) treatment, and then further improved upon this treatment (while simultaneously reducing the side effects) by dose-fractionation (splitting the dose into two).

Following our lead and with the discovery of new small molecules which also specifically bind to PSMA, European physicians have begun using these compounds tagged with the same radioactive particle. The most common molecule has been termed PSMA-617. They have shown some very nice anti-tumor responses with limited side effects. However, because European laws differ from the U.S., many men are able to pay for treatment outside of the setting of rigorous, organized clinical research studies that clearly define appropriate dosing, efficacy and toxicity.

In January 2017, research was published in the Journal of Nuclear Medicine demonstrating that Lutetium 177 combined with PSMA-617 can reduce the amount of tumors in the body and lead to remission of the cancer as measured by PSA level. Twelve German hospitals reviewed their data and compiled a publication of patients with metastatic prostate cancer who received Lutetium-177 linked to PSMA-617 (177Lu-PSMA-617). Over 18 months, 145 men whose cancer grew despite standard treatments (including abiraterone and/or enzalutamide and chemotherapy) and whose tumors “lit up” on PSMA imaging were treated. While not a proper prospective research study, they were able to determine information about both anti-tumor activity and safety. Most patients who had PSA measured before and after treatment had some decline, with 40% having PSA cut at least in half following a single treatment. Blood counts dropped in less than half (usually to moderate degrees) and some developed dry mouth and/or taste changes. Severe toxicity was rare.

It is encouraging to see that there is a treatment that might lead to reduction in cancer without severe side effects, even in men who previously have received many other lines of treatment. However, both rigorous research as well as access for our patients are current issues. Therefore, we are excited to offer a clinical trial that builds upon our prior experience of anti-PSMA radioimmunotherapy while taking into account the available European data.

This study utilizes the most commonly used molecule, 177Lu-PSMA-617, in a prospective manner. Our prior research has shown that higher doses result in significantly better anti-tumor responses, so one purpose of this study is to perform dose-escalation to determine the safest and most-effective dose without increased side effects. In addition, our research demonstrated that dose-fractionation allowed higher doses with less toxicity, so our treatment schedule will deliver the total dose in 2 fractions.

We look forward to advancing science and also making these treatments available to men in the tri-state area and across the U.S., not just those who can afford to fly to Germany for treatment. At Weill Cornell Medicine and NewYork-Presbyterian, we have an excellent, multidisciplinary team that has led the world in PSMA-targeted radionuclide therapy. We will leverage our combined expertise and experience to translate the exciting knowledge base into true clinical gains for prostate cancer patients.

To learn more about the clinical trial or enroll, click here. Call us at 646-962-2072 to make an appointment or schedule a consultation.