2018 in Review: Advancements and Accomplishments

From delivering exceptional care in the clinic, to presenting at scientific conferences and publishing research in high-impact medical journals, our Genitourinary (GU) Oncology Program had an exceptionally busy 2018. We continue to work diligently to develop new and more effective therapies to treat advanced prostate, bladder and kidney cancers, while educating the community about cutting-edge advancements in the field.

As we look back on 2018, we wish to share a brief update of our research and accomplishments. Here’s what our team has been up to over the past year.

New Faces
Most recently, we were proud to welcome Dr. Cora Sternberg, a global thought-leader in the GU oncology space, to our team. Dr. Sternberg will facilitate the continued growth and development of clinical and translational research programs in GU malignancies, as well as serve as Clinical Director of the Englander Institute for Precision Medicine (EIPM) to develop strategies to incorporate genomic sequencing and precision medicine within our Program and across Weill Cornell Medicine and NewYork-Presbyterian.


New Events
More than 200 prostate cancer patients and loved ones attended our inaugural New York City Prostate Cancer Summit, a multi-institutional collaboration between Weill Cornell Medicine, NewYork-Presbyterian Hospital, Columbia University Irving Medical Center and Memorial Sloan Kettering Cancer Center. This educational and advocacy event featured presentations and panel discussions from local medical experts and national advocacy leaders, with topics including nutrition, screening, coping and anxiety, immunotherapy and much more. Our second annual Summit is slated for September 2019 during Prostate Cancer Awareness Month. Stay tuned for details.


New Research Developments

Prostate Cancer

• Based upon our prior work with fractionated dosing of our radiolabeled antibody 177Lu-J591, we performed the world’s first phase 1 dose-escalation trial of 177Lu-PSMA-617 without finding any dose-limiting toxicity (no major side effects despite higher and higher doses), presenting the initial results at the European Society for Medical Oncology (ESMO) 2018 Congress. The phase II portion of the trial is ongoing. We are also leading the first trial combining two different targeting agents (J591 and PSMA-617) designed to deliver more radiation to tumors and less to other organs.

•  Alpha particles are several thousand-fold more potent than beta-emitters such as 177 Lu. We are completing the phase 1 dose-escalation portion of the world’s first-ever clinical trial utilizing a powerful alpha particle (225Ac) directed almost exclusively at prostate cancer cells by linking it with our J591 antibody, which avoids salivary glands.

• As prostate-specific membrane antigen (PSMA) targeting enters “prime time,” the United States Department of Defense (DOD) has recognized our significant contributions to this evolving field with a grant that will allow us to research optimal patient selection for PSMA-targeted radionuclide therapy and assess the treatment’s immune effects.

• Thanks to developing technology utilizing circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), we are able to draw information about a patient’s tumor via a simple blood test. In our findings published by the American Association for Cancer Research (AACR) Clinical Cancer Research journal, we analyzed the relationship between chemotherapy treatment and expression of androgen receptor (AR) variants in CTCs of men with metastatic prostate cancer.

• We led a phase II clinical trial through the Prostate Cancer Clinical Trials Consortium (PCCTC) and discovered that an aggressive subset of disease called neuroendocrine prostate cancer (NEPC) is driven by a gene with an associated target known as aurora kinase. Further investigation into targeting of the gene may help us to refine therapy for this difficult-to-treat patient population. Our findings were published as a cover story in Clinical Cancer Research. 

• Working with collaborators and funded by the Prostate Cancer Foundation (PCF), we have developed unique genomics sequencing methodology called PCF SELECT that allows us to identify actionable mutations in men with advanced prostate cancer.

Kidney Cancer

• The number of United States Food and Drug Administration (FDA)-approved drugs for patients with advanced kidney cancer continues to grow. Dr. Ana Molina leads our team in offering clinical trials focused on novel targeted agents, combination treatments, and risk-directed therapies for various subtypes of kidney cancer.

• Working together with the Englander Institute for Precision Medicine, we are evaluating genetic signatures from patient tumor specimens and developing organoids that can be used to test novel pathways and tailor treatment to each individual patient.

• Laboratory studies of our in vivo kidney cancer models have resulted in discoveries regarding the metabolism of the disease. Understanding the role of the mitochondria (a cell’s power generator) in kidney cancer is leading us to novel therapeutic approaches to block tumors from growing and spreading.

Bladder Cancer

• Five immune therapies are now FDA-approved for people with advanced bladder cancer. We continue research to improve upon these agents by combining them with targeted therapeutics with the potential to replace chemotherapy. Collaboration with EIPM will help us to identify tumors most likely to benefit from these treatments.

• Dr. Bishoy Faltas and his lab team are focused on understanding the role of a specific family of proteins that cause mutations (genetic errors) that may be the underlying cause of bladder cancer. This research will enable us to develop new treatments to target the newly-identified genes that drive the disease.

• Based upon Dr. Faltas’ prior high-impact Nature Genetics publication that identified the genetic mechanisms by which bladder cancers become resistant to chemotherapy and new drug targets, we are launching an innovative new clinical trial utilizing a targeted drug that inhibits bladder cancer growth, the first time this type of drug is being tested in bladder cancer.

• We are conducting clinical trials of two antibody-drug conjugates (sacituzumab govitecan and enfortumab vedotin) designed to deliver potent chemotherapy-like toxins preferentially to cancer cells. This type of therapy is anticipated to become one of the standard approaches to bladder cancer treatment.

Precision Medicine

• Using samples of patient tumors (drawn via needle biopsy), we can create small 3-D tumor representations known as organoids that mimic the way that cancer cells grow within the body and respond to treatment. Our team has worked to develop this exciting new form of precision medicine, which is especially significant for rare cancers with a lack of preclinical models available for study.

We are moving closer to our ultimate goal of curing genitourinary cancers and look forward to continued progress in the years ahead.

 

Inaugural NYC Prostate Cancer Summit

Prostate cancer is estimated to claim the lives of almost 30,000 men this year. That’s 30,000 husbands, fathers, brothers and friends.

ProstateSummit

One of our best defenses against this disease is education and awareness, granting men and their families the knowledge and power to take the appropriate steps toward optimal health and longevity.

To support this goal, some of New York City’s most prestigious prostate cancer treatment centers are joining forces to host a symposium on Saturday, September 22, 2018. This inaugural NYC Prostate Cancer Summit: An Advocacy, Awareness and Educational Event to Empower Patients and Loved Ones will be led by experts from Weill Cornell Medicine, NewYork-Presbyterian Hospital, Columbia University Irving Medical Center, and Memorial Sloan Kettering Cancer Center.

Here’s a sneak peek at some of the hot topics and expert speakers slated for this premier event.

Updates in Prostate Cancer: From Screening to Diagnosis and Treatment
Screening, Active Surveillance and Prostate Cancer Biomarkers
Douglas Scherr, MD, Weill Cornell Medicine
Elias Hyams, MD, Columbia University Irving Medical Center
Mark Stein, MD, Columbia University Irving Medical Center

Imaging, Immunotherapy and Other New Targeted Therapies
Scott Tagawa, MD, MS, Weill Cornell Medicine
Joseph R. Osborne, MD, PhD, Weill Cornell Medicine
Susan Slovin, MD, PhD, Memorial Sloan Kettering
Charles Drake, MD, PhD, Columbia University Irving Medical Center

Nutrition and Diet
Rekha Kumar, MD, MS, Weill Cornell Medicine

Coping, Anxiety and Survivorship
Andy Roth, MD, Memorial Sloan Kettering

Prostate Cancer Advocacy Panel 
ZERO: The End of Prostate Cancer – Colony Brown, Vice President of Marketing & Communications
Us TOO International – Chuck Strand, Chief Executive Officer
American Cancer Society Cancer Action Network – Michael Davoli, Director, New York Metro Government Relations

In addition to having exclusive access to these discussions, patients and loved ones will also be able to connect with fellow attendees and obtain resources related to prostate cancer treatment options and quality of life.

The Summit will run from 8AM – 1PM at the New York Academy of Medicine (on 5th Avenue and 103rd Street). It is completely free and open to all those impacted by prostate cancer. Breakfast and lunch will be provided.

Seats are limited. Reserve yours today. http://bit.ly/nycprostatesummit.

Promising Research Brings New Hope for Men with Aggressive Prostate Cancer

misha-beltra_esmo_img_2611Earlier this month, Dr. Himisha Beltran presented exciting new research results for those with metastatic prostate cancer at the European Society of Medical Oncology (ESMO)’s annual meeting in Copenhagen, Denmark. Cancer experts and patients from around the world came to the 2016 ESMO Congress to discuss the latest research and cutting-edge treatment options for people with cancer.

Dr. Beltran’s research presentation highlighted promising results from a clinical trial for men with aggressive prostate cancer. Aggressive prostate cancer sub-types represent approximately 25% of all prostate cancer cases, and neuroendocrine prostate cancer (NEPC) is considered to be the sub-type that is most resistant to currently-available treatments.

Dr. Beltran and the Weill Cornell Medicine (WCM) Genitourinary (GU) Oncology team led this multicenter, phase 2 clinical trial, which was based upon prior WCM work which identified aurora kinase A as a key target in NEPC. The trial enrolled sixty patients from across the United States. It was the first clinical trial to study a new, targeted treatment for men with NEPC. The drug used in this study, Alisertib, is an oral medication that is an Aurora Kinase A Inhibitor.

This clinical trial confirmed our hypothesis that different men’s tumors genetically expressed different levels of the targets for the drug, and as a result their response rates to this treatment varied. Those with the most optimal responses had cancers that genetically appeared to be most like NEPC in both biopsies and whole exome genomic sequencing of the tumor. As part of our Institute for Precision Medicine, we use the Exact-1 whole exome sequencing test to categorize more than 21,000 genes within the tumor. This is the most comprehensive way to determine where mutations and mechanisms for treatment resistance may exist in patients with advanced stage cancer and allows us to narrowly target different patient’s treatment regimens on the molecular level. In addition, some of the tumor biopsies were analyzed for gene expression (RNA) and organoids, which are tumor models that we are able to grow from the biopsy tissue, were developed.

In this clinical trial, we were able to learn a lot on the molecular level from the patients who had the most exceptional responses to Alisertib. Based on these results and establishing biomarkers to predict Alisertib response rates, future clinical trials could be much more targeted to include only the men whose tumors indicate that they are likely to respond to this therapy.

Additionally, there is great potential to learn much more about the tumor evolution and the biology of resistance. This clinical trial underscores the need to more narrowly focus on the sub-set of prostate cancer patients with NEPC, as there are few standard treatment options and limited clinical trials available for these men.

Thank you to all the men who enrolled in this clinical trial and helped further the field of research in the search for new cures for prostate cancer.

We’re always working to increase access to new promising treatments for NEPC and other aggressive forms of prostate cancer through clinical trials. To learn more about our open studies and to make an appointment with the Weill Cornell Genitourinary (GU) Oncology Program, call 646-962-2072.