NYC Prostate Cancer Virtual Mini Summit

The Annual NYC Prostate Cancer Summit has been taking place virtually this year as a four-part webinar series for prostate cancer patients and loved ones. We are pleased to be able to come together online while the pandemic prevents us from gathering in-person. Each part of the FREE virtual series features different topics and speakers, and offers unprecedented access to some of the field’s foremost experts! We hope you’ll join us for this webinar series.

Advances in therapeutics have led to improvements in both survival and quality of life for men with advanced or metastatic prostate cancer. Get the latest information about how physicians can more clearly detect where prostate cancer has traveled in the body and the most cutting-edge therapies for patients. Part 3 – Advanced Prostate Cancer Treatment Updates is taking place on Wednesday, May 12 at 7pm ET. The program is free to attend, but RSVP is required. Register today!

Register now – http://bit.ly/summitpart3

Mark your calendar and sign up for Part 4 – Genetic Links: Family History, Precision Medicine & More on Thursday, July 15th at 7PM ET. Precision medicine is changing the way physicians approach prostate cancer care, using information about the prostate cancer genetics and a patient’s inherited genetic makeup to develop individualized treatment plans. Cutting-edge research advances in prostate cancer biology are shaping treatment breakthroughs and guiding the development of new therapeutics and clinical trials. All prostate cancer patients and family members are welcome.

Register now – http://bit.ly/summitpart4

View Part 1 and Part 2 Webinar Recordings On-Demand:

If you missed any of the earlier webinar sessions or would like to re-watch the recordings, Part 1 “Living with Prostate Cancer” and Part 2 “Newly-Diagnosed: What Are My Treatment Options” of the series can be viewed On-Demand.

Learn more and sign up for the entire webinar program series at prostatesummit.org.

Visit http://www.prostatesummit.org to learn more and participate in this free, virtual webinar series.

Update in PSMA-Targeting for Imaging and Therapy

Prostate-specific membrane antigen (PSMA) is a protein concentrated on the surface of prostate cancer cells with limited expression on other locations in the body.  As covered previously on the blog, PSMA can be exploited for both imaging and treatment utilizing either large monoclonal antibodies or small molecule targeting agents

PSMA-targeting entails attaching a radionuclide (a particle that gives off radiation) to an antibody or small molecule designed to recognize and bind to PSMA. Research into PSMA-targeting has led to promising investigational treatments and transformed how we can detect prostate cancer. In December 2020, the U.S. Food and Drug Administration (FDA) gave limited approval for 68Ga-PSMA11 PET scans for patients with high-risk localized prostate cancer and patients with rising prostate specific antigen (PSA) levels following radiation or surgery. This form of FDA approval allowed for specific facilities in California to use this agent outside of the clinical trial environment. 68Ga-PSMA PET, which has been used elsewhere in the world without strict regulation, allows doctors to better detect recurrent and hidden prostate cancer and consequently, to choose the best type of therapy for each patient.

Weill Cornell has a dedicated team of physicians that study and interpret 68Ga-PSMA PET imaging. Numerous studies have demonstrated that 68Ga-PSMA PET is more effective than traditional scans (such as CT or MRI) in finding metastatic prostate cancer (sites where the cancer has spread elsewhere, including microscopically) and in a small head-to-head study was also better than 18F-fluciclovine (Axumin) PET/CT. There are a number of ongoing trials at Weill Cornell and elsewhere evaluating the use of PSMA targeted imaging, which currently remain the only way to obtain PSMA PET outside of California, with additional approvals of PSMA PET agents expected in the first half of 2021.

At the 2021 Genitourinary (GU) Cancers Symposium, researchers presented a head-to-head comparison of 68Ga-PSMA11 PET vs. MRI in detecting and staging localized prostate cancer (disease mainly confined within the prostate) in 74 patients. The two imaging methods had similar performance, with PSMA PET a little better for tumors outside of the prostate and MRI better for identifying tumor invasion of structures adjacent to the prostate. It may be that the combination of both methods will further enhance prostate cancer staging and a study is currently being done at WCM to evaluate this combination.

Additionally, a number of studies on PSMA-therapeutics were presented at the 2021 Genitourinary Cancers Symposium. There is an ongoing trial investigating PSMA-targeted radionuclide therapy (PSMA-TRT) with radioactive iodine in combination with the prostate cancer drug enzalutamide; radioactive iodine (Iodine-131) is conjugated to the small molecule 1095. An initial study of 10 patients receiving PSMA-directed/TGFβ-insensitive CAR-T cells (immune cells that have been engineered to recognize PSMA) demonstrated safety and efficacy. In this study, 60% of patients experienced PSA decline, ranging from 11.6 to 98.3%, and post-treatment biopsies demonstrated CAR-T cells infiltrating the tumor microenvironment. Furthermore, there is an ongoing clinical trial of a bispecific antibody (REGN5678) that connects PSMA with immune cells, which can subsequently destroy the cancer cell; this bispecific antibody is combined with a medication called cemiplimab that further strengthens the body’s immune response. 

There are multiple agents utilizing PSMA small molecules to carry the beta-emitting radionuclide lutetium-177 (177Lu) to PSMA-positive areas in the body (mostly areas of cancer spread). Updated results of a prospective head-to-head comparison of 177Lu-PSMA-617 vs. cabazitaxel (a type of chemotherapy) in 200 patients with advanced prostate cancer were presented at the 2021 Genitourinary Cancers Symposium.  In the data initially shared at ASCO 2020, the main objective was met, with more patients receiving 177Lu-PSMA-617 having PSA response compared to cabazitaxel chemotherapy.  In the updated report, patients receiving 177Lu-PSMA-617 had longer disease control (both by PSA measurements and scans), with fewer side effects and more improvements in quality-of-life. Recently, VISION, the multicenter phase III clinical trial comparing 177Lu-PSMA-617 + standard of care against standard of care alone in patients with advanced metastatic prostate cancer, has shown that patients receiving 177Lu-PSMA-617 lived longer and had longer disease control. Full results will be presented at an upcoming research conference, and we hope that this study leads to FDA approval in the future.

In general, tumors spread to other parts of the body via the bloodstream. The ability to capture these tumor cells, called circulating tumor cells (CTCs), has led to significant prognostic information along with the ability to study the cells as part of a “liquid biopsy”.  When a number of different types of therapy is able to decrease or clear CTCs from the circulation, those therapies generally make patients live longer.

Scans before and after treatment with PSMA-targeted radionuclide therapy (PSMA-TRT).

Weill Cornell researchers examined several sequential prospective clinical trials utilizing various PSMA-TRT agents. In an analysis of 116 patients, 70% treated with PSMA-TRT and with CTC counts before and after therapy had a decline in CTC counts. Some PSMA-targeting agents (i.e. the carrier molecules) may have anti-cancer effects on their own. While it appears that agents labeled with radioactive particles are more effective, some patients treated with anti-PSMA antibody J591 alone had control of CTC counts.

Alpha and beta-emitting radionuclides have different properties.  In 2020, we presented preliminary information at ASCO that a single dose of the potent alpha-emitter actinium-225 (225Ac) linked to antibody J591 (225Ac-J591) was safe, and despite lack of selection of patients with PSMA PET and prior 177Lu-PSMA therapy in the majority, 60% had PSA decline.

At the 2021 GU Cancers Symposium, investigators presented the design of WCM’s ongoing clinical trial investigating either fractionated (2) or multiple-dose (1-4 doses) of 225Ac-J591.  This study (NCT04506567) is one of many PSMA-targeted therapeutic clinical trials open at Weill Cornell Medicine and NewYork-Presbyterian Hospital.

2019 in Review: Advancements and Accomplishments

We are proud to report another year of meaningful patient connections, exciting treatment developments and continued leadership in the field of genitourinary (GU) oncology.

Check out our team’s 2019 highlights.


NEW FACESVlachostergios Panagiotis

Panagiotis “Panos” Vlachostergios, MD, PhD, has joined our team to grow GU oncology patient care and research at NewYork-Presbyterian Brooklyn Methodist Hospital. This is a significant step in our plan to bring our world-class expertise directly to patients who live in Brooklyn, minimizing their expenses and travel time to Manhattan.


NEW EVENTS

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In addition to our digital efforts to inform the patient community of the latest news and cutting-edge advancements in the GU oncology field, we also provide opportunities to learn directly from experts via free educational events. In May, Dr. Ana Molina led our first Kidney Cancer Patient Education Symposium, which allowed kidney cancer patients to connect with one another over information sessions ranging from immunotherapy treatment to anxiety management.

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Then, during Prostate Cancer Awareness Month in September, Weill Cornell Medicine and NewYork-Presbyterian Hospital teamed up with Memorial Sloan Kettering Cancer Center and Columbia University Herbert Irving Comprehensive Cancer Center to host over 300 patients, loved ones and healthcare professionals for our 2nd Annual NYC Prostate Cancer Summit. This education and advocacy event was packed with discussions about new therapies and technologies, prostate cancer genetics, post-treatment sexual health and more.

Save the Date!
Please mark your calendar for the 3rd Annual NYC Prostate Cancer Summit on September 12, 2020, and look out for a combined Kidney and Bladder Cancer Patient Education Event in 2021.


NEW RESEARCH DEVELOPMENTS

Bladder/Urothelial Cancer

• A subset of bladder cancers are driven by the FGFR gene. We led accrual of the clinical trial that resulted in U.S. Food and Drug Administration (FDA) approval of the first targeted therapy for bladder cancer, erdafitinib, which targets the FGFR gene. This research was published in the prestigious New England Journal of Medicine.

• Immunotherapy has transformed the treatment of patients with advanced bladder cancer, but, unfortunately, only a fraction of patients respond. Dr. Bishoy Faltas led a seminal publication characterizing urothelial carcinoma that originates in the “upper tract” (center of the kidney and ureter tubes). His paper deciphers why some tumors are less likely to respond to immunotherapy and explores ways to increase response rates.

• Dr. Faltas also led work that identified the genetic mechanisms by which bladder cancers become resistant to chemotherapy and new drug targets. Based on his research, we have launched a trial of an oral targeted therapy for patients who are ineligible or choose not to receive chemotherapy prior to surgery.

• We continue to lead the development of antibody-drug conjugates, which deliver potent chemotherapy preferentially to tumor cells. In this novel therapeutic approach, a monoclonal antibody binds to specific proteins found on cancer cells, allowing the attached drug to target the cancer cells without damaging the patient’s healthy cells. One of these drugs (enfortumab vedotin) was FDA-approved in December 2019, and we are studying new combinations in earlier lines of therapy. We are also leading the pivotal clinical trial designed to get one of these antibody-drug conjugates (sacituzumab govitecan aka IMMU-132) FDA-approved and made widely available to patients. Exciting trial results were highlighted at the 2019 Genitourinary Cancers Symposium and the 2019 Congress of the European Society for Medical Oncology (ESMO).

Prostate Cancer

• Our team is at the forefront of utilizing prostate-specific membrane antigen (PSMA)-targeted therapies in the treatment of prostate cancer, currently one of the most exciting research areas in the field. We anticipate that our clinical trials will lead to FDA approval of at least one drug in the near future.

• Based upon prior work with fractionated dosing of our radiolabeled antibody 177Lu-J591, we performed the world’s first dose-escalation trial of 177Lu-PSMA-617, with results presented at the 2019 ESMO Congress. Our unique dose-dense regimen was well tolerated, with nearly 82 percent of men experiencing prostate-specific antigen (PSA) decline.

• We also completed the dose-escalation portion of the first alpha emitter (225Ac-J591) trial and will soon present the early results publicly. At the end of the year, we were notified of grant funding for an exciting future trial using this approach in combination with immunotherapy.

Kidney Cancer

• As the number of FDA-approved advanced kidney cancer drugs grows, our team remains focused on developing novel drug combinations and identifying which patients should be treated with which therapies in order to achieve the best outcomes. Our goal is to improve responses and decrease resistance to treatment by providing patients with unique combination therapies and genomic-driven targeted agents.

• Dr. Ana Molina is leading an exciting study of the antibody OX40 in combination with axitinib. Clinical and non-clinical observations suggest that combining the OX40 antibody – which stimulates the immune system and may stop cancer cells from growing – with axitinib may produce superior anti-tumor activity compared to one drug alone. This approach is being tested specifically in patients whose tumors have grown despite standard immunotherapy.

Precision Medicine

A major goal of our research is precision medicine, or the tailoring of therapy to an individual patient. Under the direction of Dr. Cora Sternberg, we continue to analyze genomic signatures, or unique tumor “fingerprints,” in patient tissue and blood samples to assess for real-time treatment targets and to discover new mechanisms of resistance to current therapies. A treatment target that we identified in an aggressive subset of disease termed neuroendocrine prostate cancer (NEPC) is making its way into clinical trials. In addition, we are spearheading work to develop organoids (mini 3-D cancer models) from patient tumor biopsies in order to test novel pathways and enhance drug development.

We look forward to persistent progress in 2020 and in the years ahead.

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