A Drive to Help Patients Launches a Career in Revolutionizing Prostate Cancer Care

Howard I. Scher, MD, never doubted his desire to become a doctor. However, an impromptu lecture ultimately sent him down the path toward a career in oncology.

While Scher was at New York University (NYU) School of Medicine, one of his mother’s teacher colleagues was diagnosed with lymphoma, prompting Scher to approach Robert Silber, MD, NYU’s then head of hematology, on their behalf.

Silber shared advice before asking Scher if he had personally done any research in the lymphoma space. Silber invited Scher to attend a medical meeting in New Jersey. After having seen 2 patients with refractory leukemias at NYU at the meeting, Scher spoke with Emil J. Freireich, MD, of The University of Texas MD Anderson Cancer Center in Houston, about potential treatment options for these patients. Freireich, a 2015 Giant of Cancer Care inductee in lymphoid neoplasms, explained that there were early-phase treatment programs available in Houston.

Scher returned to Silber and proposed bringing these patients to MD Anderson to be considered for enrollment in the studies. Silber agreed, but on one condition: “You have to give us a lecture before you go,” Silber told Scher.

“To prepare, I read whatever I could get my hands on about the topic, realizing that was it would not the state of the art, because it [was in print. But the difference was, they saw that I could talk the language and knew something about it,” Scher said, “which led to an invitation to do a fellowship program for fourth-year students, to which enabled me to spend 4 months of my last year of medical school at MD Anderson. The experience was exceptional on many levels, one of which was the start of the start of disease-focused clinics for the first time.”

Following his residency at Bellevue, Scher applied for an oncology fellowship at Dana-Farber Cancer Institute in Boston, Massachusetts, and Memorial Sloan Kettering Cancer Center. MSK was the winner, and after completing a rotation in radiation oncology, his second rotation was with Alan Yagoda, MD—a pioneer in genitourinary cancers.

What was interesting was that Yagoda gave Scher advice that shaped the remainder of Scher’s career. The rest, as they say, is history.

“He simply stated: ‘I just want you to know prostate cancer is going to be a growth industry, and you should go into it. There are too many oncologists focusing on lung, breast, and colon cancer. So there it was. Who knew any better?” Scher said.

The PSA of It All

As Scher began treating patients with prostate cancer, tests to measure prostate-specific antigen (PSA) levels did not yet exist and CT scans to see inside the abdomen were still a novel technique. When the discovery of PSA was officially patented in 1984, it shifted the focus of Scher and colleagues in their research with respect to how treatments could be developed for prostate cancer.

“When PSA first came out, all of a sudden, patients who thought they were cured having had surgery and no symptoms, saw the levels rising, an indicator that the cancer was growing,” Scher said. “I’m an oncologist looking to develop drugs and of course. I’d rather treat people early, before they have symptoms, But what we had to ask was: could the rate of change in PSA help us identify those who needed treatment because their cancers were likely to spread, cause symptoms, or shorten life expectancy?”

Scher started speaking with the National Cancer Institute regarding the use of changes in PSA levels in clinical trials. At the time, the requirement for enrollment on trials was measurable disease, which occurs infrequently, excluding patients with disease limited to bone, the most common site of spread. Scher and colleagues wanted to demonstrate how to use PSA levels to inform the need for treatment and whether the treatment was working.

As more became known about the biology of prostate cancer, it became clear to Scher and others that developing new clinical trials to treat patients with the disease was paramount. Conversations with the Prostate Cancer Foundation, founded by Michael Milken, led to investments and resources for discovery, preclinical model development and a better understanding the genomic alterations involved in prostate cancer and how to target them.

“We decided as a community to come together. I noticed that it was hard to collaborate. People wanted to, but we had to go through all the bureaucracy,” Scher said. “Shortly after that, about 8 or 9 years into it, the PCF and the US Department of Defense (DOD) Prostate Cancer Research Program (PCRP) issued a competitively awarded mechanism, which launched the Prostate Cancer Clinical Trials Consortium (PCCTC). The PCCTC in turn established a novel infrastructure that enables transparent project co-development between investigators, research sites, and industry partners. The idea was to accelerate drug development, and that was started in 2005 as a 3-year grant. Eighteen years and multiple grant renewals later I continue to serve as the PI of the PCCTC, which is not only recognized as the nation’s premier prostate cancer clinical trials group, but as an institution in which the next generation of prostate cancer clinical research leadership is being developed. We started with the 8 centers. We now have 99 and are continuing to grow.”

Scher has also participated in the various iterations of the Prostate Cancer Clinical Trials Working Group (PCWG), serving as the lead of PCWG2 and PCWG3, which are an international collaborations focused on developing standards for phase 2 clinical trial designs and analyses, based on the state of the biologic understanding of the disease and biomarkers to better inform medical decision making.

Plans are underway for the PCWG4, in which Scher hopes to continue his work in designing innovative trials and improving outcomes and quality of life for patients with prostate cancer.

“We have an exceptional team of experts in the field who really put the effort into [research],” he said. “They have been helpful in terms of trial design and dealing with issues. We get questions all the time and these groups give consistency, which is very important.”

Revolutionizing Prostate Cancer Care

Scher and colleagues worked to standardize clinical trials for prostate cancer and develop treatments beyond chemotherapy. His work led to pivotal drug testing and FDA approvals that shifted the treatment paradigm for these patients.

Findings from a phase 3 trial (NCT00638690) demonstrated that treatment with abiraterone acetate (Zytiga) plus prednisone generated an improvement in overall survival (OS) compared with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) who were previously treated with docetaxel.¹ This study led to the initial FDA approval of abiraterone in 2011.²

“The original plan was to test it in the first-line setting. I suggested [testing] it after chemotherapy because PSA [levels] were still going up and patients were still responsive,” Scher said.

Further, in collaboration with the FDA, this phase 3 study also led to the development of a circulating tumor cell (CTC) biomarker panel designed to measure CTC and lactate dehydrogenase levels to serve as an individual surrogate to predict survival outcomes for patients with mCRPC.³

Scher also spearheaded the protocol and development of enzalutamide (Xtandi) for patients with mCRPC, and findings from the phase 3 AFFIRM trial (NCT00974311) showed that the agent prolonged OS vs placebo for these patients who were previously treated with chemotherapy.⁴ Enzalutamide was approved by the FDA in 2012.⁵

In 2017, having served as the chief of the Genitourinary Oncology Service at MSKCC for 25 years, Scher was tasked with launching the Global Biomarker Development Program at MSKCC. The program was designed to accelerate the development and approval of biomarker tests and technologies to better inform medical decision-making and ultimately improve patient outcomes. The program has expanded in recent years with a focus on liquid biopsy imaging, with a primary goal of developing more precise liquid biopsy tests to detect and profile circulating tumor DNA and other biologic components, or circulating tumor cells. The program comprises medical oncologists, radiation oncologists, surgeons, radiologists, pathologists, geneticists, and computational biologists.

The genomics group at MSKCC is housed in the Center for Molecular Oncology, wherein somatic and germline profiling is performed using an FDA and NYS approved test, MSK-IMPACT, that has passed the 100,000 mark of samples analyzed. Scher said this made an an unparalleled impact on patient management.

Along with initiating PCWG4 to continue to innovate and create a broader consensus on the design of clinical trials for patients with prostate cancer, Scher said he hopes to accelerate drug development by creating an adaptive trial structure for patients who present with high-risk disease that use biomarker readouts to better identify individualized treatment plans for patients.

“I would say I work hard, but I don’t consider this as work. With everything changing in the field so quickly, it’s just fascinating,” he said. “My very first paper [delved] a little bit into immunology when I was working with the immunology group at the Weitzman Institute group in college. And now to see what was happening in the field of immunology in oncology, it is transformative.”

Prostate Cancer Hits Home

In 1999, Scher’s father in law was diagnosed with prostate cancer. That encouraged Scher to eat healthier and take up distance running, and in 2000, he entered the New York City Marathon lottery, got a start, ran the race, and loved it,” Scher said. “It’s exhilarating when you do it. The energy in the city on a marathon day is unparalleled, it’s 26 miles of people. I’ve done 8 marathons now, so it’s not too bad. I’ve made a lot of good friends and met good people, and [running] is a wonderful way to see places that you’re traveling to.”

As far as habits picked up during a midlife crisis, these weren’t the worst, Scher quipped.

Seven of those marathons took place in his native New York. He also ran the Boston Marathon in 2014—the first race after the Boston Marathon bombing in 2013.

“There was a real, emotional sympathy between [Boston and New York] because we’re normally combative when it comes to our [sports] teams. That was a very special day,” Scher said. “The theme centered around everyone finishing. It was an amazing day.”

Scher married his wife, Deborah, in 1989, and the couple has 3 children, Jeremy was the first, followed by twins, Isabel and Daniel.

Throughout his career, Scher used his travel as more than just an opportunity to squeeze in the occasional run around a new city. As he traveled to various cities across the globe, he made a conscientious effort to carve out extra days and bring at least one of his children along for the journey, giving him a chance to bring the two most important aspects of his life together.

Clinicians referring a patient to MSK can do so by visiting msk.org/refer, emailing referapatient@mskcc.org, or by calling 833-315-2722.

References

1. Fizazi K, Scher HI, Molina A, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012;13(10):983-992. doi:10.1016/S1470-2045(12)70379-0
2. Zytiga. Prescribing information. Janssen; 2020. Accessed August 11, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/ label/2020/202379s031s033lbl.pdf
3. Scher HI, Heller G, Molina A, et al. Circulating tumor cell biomarker panel as an individual-level surrogate for survival in metastatic castration-resistant prostate cancer. J Clin Oncol. 2015;33(12):1348-1355. doi:10.1200/JCO.2014.55.3487
4. Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367(13):1187-1197. doi:10.1056/NEJMoa1207506
5. Xtandi. Prescribing information. Astellas; 2018. Accessed August 11, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/ label/2018/203415s014lbl.pdf