April brings more than just showers – the month kicks off with a very important cancer research conference. Tomorrow we are headed to Washington, DC for the American Association for Cancer Research (AACR) annual meeting held April 1-5, 2017.
Our team will be joining approximately 20,000 cancer researchers from across the country and around the world for this important meeting. Several physicians and scientists from Weill Cornell Medicine, NewYork-Presbyterian, and the Meyer Cancer Center again served on the scientific program committee, including our own Dr. Scott Tagawa.
We have a lot to share at AACR 2017, so please check back frequently as we’ll be updating the blog regularly throughout the week.
Here are some additional highlights of what’s to come:
Updates regarding circulating tumor cells (CTCs) and the role of biomarkers in non-invasive diagnostics and treatments
How organoids may help us better treat neuroendocrine prostate cancer (NEPC)
The different types of radiation used to treat prostate cancer and how we’re targeting PSMA – a marker on the surface of most prostate cancer cells – with radioimmunotherapy to kill cancer cells
The latest updates in bladder cancer research, including updates in genomics and targeting molecular pathways
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:
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.
April brings more than just showers – the month kicks off with a very important cancer research conference. Tomorrow we are headed to Washington, DC for the American Association for Cancer Research (AACR) annual meeting held April 1-5, 2017.
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