Motzer Helps Set the Pace of Discovery in Kidney Cancer Research

Robert J. Motzer, MD

Robert J. Motzer, MD, is a pioneer in the world of kidney cancer.

When he was hired in 1988 as a medical oncologist specializing in both testicular and kidney cancer at Memorial Sloan Kettering Cancer Center (MSK), kidney cancer was seen as one of the least desirable areas of oncology.

“There were doctors at the center who cared for patients with advanced kidney cancer, but for none of them was this disease their main priority,” said Motzer, 63. “When I came on to the faculty, it was considered to be one of the most difficult cancers to treat and associated with a poor prognosis.”

More than 25 years later, Motzer has helped transform the disease into a chronic condition, with some patients living longer than ever before possible. His efforts to identify which patients are most likely to do well taking particular medications, the establishment of a clinical research foundation focused on kidney cancer, and his research on new and evolving drugs—including leading more than 75 clinical trials—have all helped to push standards forward for those affected by renal cell carcinoma (RCC) and those with testicular cancer.

Motzer’s research has contributed to bringing 8 therapies to market to help treat advanced RCC: sunitinib (Sutent), pazopanib (Votrient), axitinib (Inlyta), temsirolimus (Torisel), everolimus (Afinitor), nivolumab (Opdivo), cabozanitib (Cabometyx), and lenvatinib (Lenvima).

Paving the Way

His own focus has guided him toward excellence throughout his life. “My favorite quote is, ‘Always take the high road and maintain my standards,’ in patient care, clinical research, and all aspects of my life,” he said. “I’ve been doing this for almost 30 years, and I’ve taken care of thousands of patients with kidney cancer. I’m very committed to providing the people with the best care. The infrastructure at MSK, including the surgeons, radiologists, pathologists, and others, really contributes to that.”Motzer grew up in Glen Rock, New Jersey, and was always interested in science and helping others. Following high school, he attended Hope College, a liberal arts school in Michigan, and carried out an organic chemistry synthesis research project one summer that was backed by a grant from the National Institutes of Health. “I can’t recall any publications from it, but it got me interested and involved in doing and performing research,” he said. It would be the first of dozens of research projects he would eventually take part in and oversee.

Hope College was also where Motzer met his wife, Sara; they have been married for nearly 40 years and reside in Ridgewood, New Jersey. “She’s been with me through the whole process,” he said. Together, they have 3 children: Kate, Rachel, and Andrew.

After Motzer graduated from Hope in 1977, he went to medical school at the University of Michigan; he first took note of patients with cancer during clinical rotations in the Oncology/Hematology Service. “It was largely based on the high unmet need for good care for patients,” he said. “In the 1980s, we were really limited. There was very little to offer patients with advanced cancer, except for highly cytotoxic chemotherapy drugs.”

Through residencies at North Shore University Hospital in Manhasset, New York, and MSK, followed by an MSK fellowship, Motzer focused on giving patients a high level of care, with an emphasis on oncology and medical trials. At MSK, he met his mentor, George Bosl, MD, who focused on genitourinary cancers, clinical trials, and academic medicine.

Mentoring Milestones

“He had high standards for patient care, and he was dedicated to mentoring junior faculty, research, and education, and those became my priorities as well,” said Motzer. The two remain colleagues. Bosl became the head of the Genitourinary Department and (from 1997 until 2015) was chair of MSK’s Department of Medicine.Like Bosl, Motzer continues to value mentoring the next generation of oncologists. Over the years, he has mentored at least 15 to 20 fellows at MSK, many of whom have established themselves in their own academic careers.

It’s a way of paying it forward, as Motzer noted his own benefits as a mentee. “I received good mentorship with research in college and with George Bosl, and I made a commitment to follow through with that to help mentor others as well.” To honor his work, Motzer won grants from the National Cancer Institute for 5 years, from 1999 to 2004, for his teaching and advising medical oncology fellows about genitourinary tumors. Motzer has also been honored elsewhere for his oncology achievements. He earned the Career Development Award from the National Institutes of Health, the Willet F. Whitmore Award for Clinical Excellence from MSK, and the Eugene P. Schonfeld Award from the Kidney Cancer Association.

Innovative Efforts

He chairs the National Comprehensive Care Network Kidney Cancer Guidelines Panel; has published more than 500 original articles, scientific reviews, chapters, and abstracts; and has spoken globally about his work, including lectures in Japan, China, Russia, Brazil, Germany, Spain, and Turkey.Motzer’s role in developing and studying which medications can further help patients with metastatic RCC has been significant. He established the MSK Risk System, also known as the Motzer Score, in 1999, by studying the results of 670 patients with renal cancer who were part of clinical drug trials using interferon and interleukin-2. Working with MSK colleagues, Motzer determined which patients were most likely to have the highest and lowest survival rates based on 5 elements: levels of hemoglobin, calcium, and lactate dehyrogenase; performance status; and the time from diagnosis to systemic treatment.

Before the risk system was used, “people at different centers were speaking different languages about the results patients had with different drugs,” Motzer said. Today, it is used internationally to determine which patients with advanced RCC are the best candidates for particular clinical trials and how effective drug treatments are in patients already involved in research trials.

Motzer was also the lead clinical investigator for phase II and III clinical trials for sunitinib, a pivotal drug that helped “open up a new era” of kidney cancer treatment. “I had seen one patient after another progress on previously studied drugs,” he said. “It was clear in the first sunitinib study, with the very first patient, that there was a high level of activity in this disease, its prognosis, and in the clinic,” he said.

Exploring Combinations

After the results were published, first in the Journal of Clinical Oncology in 2006 and later in The Journal of the American Medical Association and the New England Journal of Medicine, Motzer worked to help design trials for new targeted therapies. Eventually, other drugs were granted FDA approval to help patients with advanced kidney cancer, including sorafenib (Nexavar), axitinib, temsirolimus, everolimus (Afinitor), nivolumab, cabozanitib, and lenvatinib.In his recent work, Motzer has been seeking to expand frontline options beyond sunitinib, particularly with checkpoint blockade immunotherapy and novel combinations. “There’s a high unmet need to develop better treatments for first-line kidney cancer,” he said in a recent interview.

In February, Motzer presented findings from the phase III study IMmotion151 study demonstrating that the combination of atezolizumab (Tecentriq), a PD-L1 inhibitor, and bevacizumab (Avastin), an anti-VEGF antibody. reduced the risk of progression or death by 26% compared with sunitinib for patients with untreated PD-L1—positive RCC. After 15 months of median follow-up, the median PFS was 11.2 months with atezolizumab and bevacizumab compared with 7.7 months with sunitinib. “For an aggressive cancer like this, where less than 20% of people survive 5 years after diagnosis, we think a 3.5-month longer progression-free survival, given the tolerability for this new combination treatment regimen, is an important development,” Motzer said.

Looking forward, Motzer is excited about the prospects for combining immunotherapy and targeted therapies. “I think it’s a very promising approach,” he said. “We need to develop combinations if we want to increase the durable remission rate.” He also is developing a new MSK program with Timothy A. Chan, MD, PhD. They will identify biomarkers that determine who will and will not respond to treatment approaches. “These areas are all desperately needed,” said Motzer.

With his clinical care, mentoring, and research efforts, Motzer looks forward to seeing even more innovations in the field. Although there is not yet any screening tool that can help predict kidney cancer, Motzer is still hopeful that breakthroughs are coming, particularly through others who are also working in the field, some his former mentees.

“My hope is that we continue to develop new targeted drugs and new immune treatments to increase the complete remission rates and survival rates with treatment, and subject patients to fewer adverse effects,” he said. “I think the younger clinical investigators are our future, and it’s important to guide and help them so they can have productive careers and make further achievements and headway.”