Studies Highlight Erdafitinib as an Encouraging Bladder Cancer Treatment Option

It has been an especially exciting time for our Genitourinary (GU) Oncology Program. Our team’s bladder (urothelial) cancer research recently made its way into two prestigious medical journals, with both studies highlighting erdafitinib – an oral inhibitor of fibroblast growth factor receptor (FGFR) – as an encouraging therapeutic option for the disease.

FGFR gene alterations are common in urothelial carcinoma and may be associated with low sensitivity to immunotherapy.

In a phase II study of 99 adults with locally advanced or metastatic urothelial carcinoma harboring FGFR gene alterations, Dr. Scott Tagawa and colleagues found erdafitinib to demonstrate impressive tumor control and tolerability. Forty percent of patients responded to the drug, and among the 22 patients who had previously received immunotherapy without success, the response rate jumped to 59 percent.

Weill Cornell Medicine“While not yet confirmed by randomized trial results, the fact that these patients with the unique molecular tumor selection were responsive to erdafitinib and resistant to prior lines of standard therapy makes this a pivotal study,” said Dr. Tagawa. “It’s wonderful to now have this option available for our patients early while awaiting results of the confirmatory randomized trial. It highlights the importance of genomic tumor testing.”

The research group’s findings were published in the New England Journal of Medicine and led to accelerated approval of erdafitinib as the first targeted drug for urothelial carcinoma from the United States Food and Drug Administration (FDA).

In addition to the use of next-generation sequencing of tumors to more precisely select those most likely to respond, the standard erdafitinib regimen also utilizes individualized dosing. Erdafitinib, partly depending on the dose used, is shown to induce increased phosphorus levels in the blood. As blood phosphorus levels are related to targeting of the key pathway (FGFR), the dose of erdafitinib is increased if phosphorus levels do not significantly increase in the absence of any significant side effect. In a retrospective analysis presented at the 2019 European Society of Medical Oncology (ESMO) annual meeting, erdafitinib-treated patients with increased blood phosphorus levels had improved outcomes.

Under the leadership of Dr. Bishoy Faltas, an in-depth analysis of the nuanced molecular characteristics of upper-tract urothelial carcinoma (UTUC) – an aggressive cancer occurring in the lining of the ureter and kidney – supports that erdafitinib has potential to improve the effectiveness of immunotherapy in this patient population.

Whole-exome and RNA sequencing of UTUC patient tumors yielded a number of insights into the biology of the disease – chiefly that it has low immune cells (T cells) and high expression of FGFR3. The research team found that inhibiting FGFR3 with erdafitinib increased the activity of BST2, a gene associated with immune system activation. Thus, combining FGFR3 inhibitors such as erdafitinib with a class of immunotherapy drugs called PD-1/PD-L1 inhibitors can serve as a viable treatment strategy for UTUC in the future.

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“By inhibiting FGFR3, we are able to stimulate genes that are associated with activation of the anti-tumor immune response,” said Dr. Faltas. “In the future, we could potentially use this strategy to reverse the T-cell depletion in these tumors.”

Findings from Dr. Faltas et al. were published in Nature Communications.

Erdafitinib is under further investigation and development in an ongoing clinical trial at Weill Cornell Medicine and NewYork-Presbyterian.

A Phase 1b-2 Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Erdafitinib Plus JNJ-63723283, an Anti-PD-1 Monoclonal Antibody, in Subjects with Metastatic or Surgically Unresectable Urothelial Cancer with Selected FGFR Gene

We are proud to draw upon our longstanding expertise in the bladder cancer field to lead advancements in the understanding and care of this disease, and we hope that sharing our findings will prompt additional discoveries.

 

The Pathologist’s Crucial Role in Cancer Care

By Francesca Khani, MD

Some say that in medicine, healing begins with a diagnosis. Pathologists – physicians who work in a laboratory to examine samples of body tissue for diagnostic purposes – play a tremendously important role in determining a patient’s treatment plan, even though they usually do not directly interact with patients.

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Pathologists act behind the scenes, consulted by doctors in other specialties to render a diagnosis so that a patient’s disease can be managed appropriately. Armed with an accurate diagnosis, the treating physician can present the patient with the best therapeutic options.

There are many different types of pathologists, encompassing a wide range of laboratory medicine fields. Anatomic pathologists specialize in evaluating tissue or cell samples from patients and are responsible for diagnosing diseases. Samples range in size from collections of individual cells (such as a pap smear), to biopsies (removal of a small piece of tissue), to entire organs removed during surgery. These cells or tissue samples are traditionally evaluated under a microscope for the diagnosis of a variety of diseases, including cancer.

Pathology at Weill Cornell Medicine and NewYork-Presbyterian Hospital (WCM/NYP) is highly sub-specialized such that each pathologist has disease-specific expertise. In particular, we have multiple pathologists trained in and dedicated to evaluation of genitourinary (GU) malignancies, including prostate, bladder, kidney and testicular cancers.

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In patients suspected to have a GU cancer, pathologic evaluation is critical to initiate a treatment plan (e.g. surgery, chemotherapy, and/or radiation). Accurate assignment of a tumor grade (based on aggressiveness) and stage (based on the extent of the tumor) is essential to determining the patient’s prognosis and informing the most effective disease management plan. Some prostate or kidney cancers, for example, may be indolent (slow-growing) and can be safely monitored without treatment, instead of requiring immediate surgery or radiation treatment.

In some cases, the diagnosis is straightforward and can be determined easily from examining the first set of microscopic slides created from the tissue. In other cases, when the appearance of the tissue under the microscope may be more ambiguous and difficult to interpret, a team of pathologists will work together to reach a consensus on the diagnosis. Sometimes additional testing is necessary, such as the application of special stains that contain antibodies which reveal the presence or absence of certain proteins, aiding pathologists in determining the correct diagnosis. Other testing examines the genetic profile of the tissue. At WCM/NYP, we routinely perform a comprehensive genetic characterization of a patient’s tumor, which can inform next steps if actionable molecular targets are identified.

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GU pathologists at our institution implement a highly collaborative approach to patient care and are in close, constant communication with colleagues in urology, medical oncology, radiation oncology and beyond to discuss the nuances of individual patient cases. These discussions take place at regularly scheduled multidisciplinary meetings and as needed throughout our work. Open lines of communication among the various GU physician stakeholders truly helps to optimize care for people with these diseases.

The GU Oncology Program’s commitment to excellence runs deep – behind the scenes and beyond the exam room. Our pathologists’ hard work to secure the right diagnosis pays off in dividends when it puts patients on the fast track to receive the treatment most likely to act against their disease and produce the best health outcomes.

 

Join Us: 2nd Annual NYC Prostate Cancer Summit

ProstateCancerSummit_Postcard.BlogThe Inaugural New York City Prostate Cancer Summit in 2018 granted us the ability to educate and empower nearly 250 prostate cancer patients, loved ones, healthcare professionals and community members with the latest updates in the field. Following the success of last year’s event, Weill Cornell Medicine, NewYork-Presbyterian Hospital, Columbia University Irving Medical Center and Memorial Sloan Kettering Cancer Center are joining forces again to host the 2nd Annual NYC Prostate Cancer Summit on Saturday, September 21, 2019. 

The Summit will take place from 8AM – 2PM at the New York Academy of Medicine on 1216 5th Avenue, New York, NY 10029. The event is free and open to all patients and loved ones impacted by prostate cancer.

RSVP is required. Reserve your seat today: http://bit.ly/nycprostatesummit19

We are pleased to offer a fresh slate of presentations based on audience suggestions from last year’s event. Here’s your first look at the topics on tap.

Introductory remarks by David Nanus, MD, of Weill Cornell Medicine/NewYork-Presbyterian Hospital 

The Latest Therapies and Technologies for Diagnosing and Treating Prostate Cancer

Cora Sternberg, MD – Treatment Overview
Weill Cornell Medicine

Jim Hu, MD – Focal Therapy
Weill Cornell Medicine

Sean McBride, MD – Hypofractionation (short course) Radiation
Memorial Sloan Kettering Cancer Center

Charles Drake, MD, PhD – Immunotherapy and Other Targeted Therapies
Columbia University Irving Medical Center

Moderated by Mark Stein, MD, of Columbia University Irving Medical Center

What Your Genes Really Mean: Examining Family History, Prognosis and Outcomes

Feighanne Hathaway, MS, CGC
University of Chicago Medicine

Coping with Side Effects and Maximizing Quality of Life

Joseph Alukal, MD – Sexual Health and Incontinence
Columbia University Irving Medical Center

Guy Maytal, MD – Anxiety
Weill Cornell Medicine

Moderated by Susan Slovin, MD, PhD, of Memorial Sloan Kettering Cancer Center

Is A Clinical Trial Right for You? Advancing Prostate Cancer Research

Scott Tagawa, MD, MS, Weill Cornell Medicine

Dina Lansey, MSN, RN, Johns Hopkins Sidney Kimmel Cancer Center

Ed Randall, Fans for the Cure

Moderated by Jonathan W. Simons, MD, of the Prostate Cancer Foundation