The Magnificence of the Possible: Toni K. Choueiri Gets Giants of Cancer Care Award in GU Cancer

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Partner | Cancer Centers | <b>Dana-Farber</b>

It is a life-changing experience to see people take the hurt, suffering, pain, and loss of cancer and transform it into a superhuman force for good and for hope.

Each year, the Pan-Mass Challenge, a bike-a-thon that spans a significant swath of Massachusetts, raises more money for a philanthropic cause than any other athletic fundraiser in the United States. Every penny of the proceeds goes toward funding research at the Dana-Farber Cancer Institute aimed at a significant goal: finding a cure for cancer.

The Challenge began in 1980. Nearly 7000 riders take part in the 200-mile event annually, raising more than $767 million. One of those riders is Toni K. Choueiri, MD.

Choueiri has an impressive résumé: director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute/Brigham and Women’s Hospital and director of the Kidney Cancer Center, the Jerome and Nancy Kohlberg Chair, and professor of medicine at Harvard Medical School in Boston, Massachusetts. One of his proudest entries on it, however, is 4-time rider in the Pan-Mass Challenge.

The ride is close to his heart for obvious reasons, but bike riding, especially long distance, was not an easy hobby to master. Especially for someone who had barely touched a bicycle since he was 12 years old.

“It took a lot of preparation to know how to get on the bike, to buy the right bike, to figure out how to clip—which is a pain,” Choueiri said. “But the biggest obstacle proved to be the roads in and around Boston.”

Choueiri recalled on one of his first trainings, taking a wrong turn and ending up along the shoulder of a major highway. “Don’t do that,” he cautioned. “My mind was probably on something else at the time.”

Stay Safe, Get Educated

As a child, Choueiri had few opportunities for activities like bike riding. He was born in Lebanon, and until he was 15 years old, the country was entrenched in a bloody civil war.

“These memories are not bittersweet. They are bitter,” he noted. “The primary concern of my parents was our safety, and they were preoccupied with it all day every day. There were a lot of scary parts and uncertainty. Thanks to their efforts, we survived and never lost focus on the future and the importance of our education.”

Choueiri channeled his energy into his studies. Even as a child, he’d already decided medicine and science were in his future. He remembers being intrigued by the first data on DNA and RNA to read out, but mostly, he recalls knowing from a young age that education and a profession in medicine were, among many other things, practical and noble.

“There was a lot of respect for the profession of medicine in my home country. When you grow up in a dire situation, or a situation of instability, you do not have many options,” Choueiri explained. “Even growing up, I always felt, and this is something my parents taught me, that it is good to help others, to work hard, and to commit yourself to the pursuit of something greater—for me this was the world of medicine.”

As it happened, Choueiri was a gifted student and attended a French medical school, Saint Joseph University Faculty of Medicine, in Beirut. His sights, however, were set on the United States, where research opportunities were plentiful.

His “American birth,” as he calls it, happened in 2001 in Ohio at Cleveland Clinic, where he did his residency in internal medicine and fellowship in hematology/oncology. He would eventually pivot to focus specifically on genitourinary oncology.

After spending 6 years at Cleveland Clinic—and working with “giants” in the field such as Derek Raghavan, MD; Robert Dreicer, MD; Ronald M. Bukowski, MD; and many others—Choueiri decided it was time for a change. In 2007, he went east to Boston, Massachusetts, and Dana-Farber Cancer Institute. Choueiri has spent much of his adult life and professional career in Boston, but his time in Cleveland remains near and dear to him.

“Cleveland rocks!” he declared fondly. “I’m still a hard-core Cleveland sports fan...except for the Red Sox. You can’t work a mile away from Fenway Park and not root for the Red Sox.”

Stay Agile

Choueiri began as an instructor at Dana-Farber and moved quickly up the ranks. In 2016, he took over as director of the Lank Center for Genitourinary Oncology, which focuses on all areas of care for prostate, bladder, testicular, and kidney cancers. He became a full professor at Harvard Medical School in 2018.

According to Choueiri, his contributions to the field of genitourinary oncology can be thought of as a play in 3 acts—the first act being the clinical development of the novel agent cabozantinib (Cabometyx).

“Our group had the privilege of driving this drug from the phase 1 trials through phase 3 and then on to several combination studies,” Choueiri said. The development of cabozantinib led to a moment he considers a career highlight: a 2010 phone conversation with his friend and mentor William G. Kaelin Jr, MD. Choueiri was venting about what seemed at the time like a stall in the renal cell carcinoma (RCC) treatment paradigm following the advent of multiple VEGF inhibitors.

“I said to Bill, ‘We have to do better than VEGF. What are you working on?’ ” Choueiri recalled.

Kaelin, cowinner of the 2019 Nobel Prize in Physiology or Medicine for discovering how cells sense and adapt to oxygen availability, directed Choueiri to several articles published years earlier suggesting the MET pathway as a potential direct therapeutic target in clear cell RCC. That was all the prompting Choueiri needed. He swiftly got to work looking for companies developing both VEGF and MET inhibitors, ultimately landing on a company called Exelixis, Inc; the company was doing drug-drug interaction studies with a novel oral receptor tyrosine kinase inhibitor that would eventually become known as cabozantinib. After many phone calls, Choueiri convinced the company to include an RCC cohort in their trials.

Years of research culminated in the 2016 FDA approval for cabozantinib, based on results from the phase 3 METEOR trial (NCT01865747). The agent has since received FDA approval in multiple indications, most recently in combination with nivolumab (Opdivo) for patients with advanced RCC based on results from the phase 3 CheckMate 9ER trial (NCT03141177).

For his second act, Choueiri traveled back to his time at Cleveland Clinic, where he worked with colleague Daniel Heng, MD, to establish the International Metastatic RCC Database Consortium (IMDC). The IMDC now includes data from 15,000 patients with metastatic RCC, many with available tumor tissue.

“We asked a lot of important questions about RCC,” Choueiri explained. “We were not just doing a simple prognostic model for patients with VEGF-targeted therapy. We were bringing up the concept of primary refractory disease, prognostic models in non–clear cell patients, previously treated patients, looking at patients with sarcomatoid histology, etc.

”Finally, the third act is what Choueiri jokingly refers to as the “microenvironment” of Dana-Farber Cancer Institute. With his team, he had fostered an environment focused solely on clinical and translational research and developments aimed at improving patient outcomes in RCC and other genitourinary cancers.

“I remember very well some of the first trials where it was fine to randomize metastatic patients to placebo. There was really nothing for them,” Choueiri said. “Before the first wave of the drugs that really work in RCC appeared around 2005, the median survival, even for patients on clinical trials who were in relatively good shape, was around 1 year.

“Now, you read a clinical trial today and the median survival is not reached. And when you look at a study for a long time, we’re looking at 4 to 5 years. This is how kidney cancer was transformed, through novel drugs and clinical trials.”He credits many of his clinical wins to his team.

He may be the boldface name, but it takes colleagues, fellows, research assistants, advanced practitioners, and nurses to drive the science forward.

"What I am most proud of [is mentoring doctors]. It’s something I take pride in, not just mentoring, but also collaborating with a team of people from all over the world to create something new and to play off each other’s energy and to learn together,” he said.

Choueiri meets with his team weekly to discuss research developments in RCC and to brainstorm future research directions. And while he manages the day-to-day minutia bosses are often saddled with, he trusts his team to provide a hands-on approach in clinic, where multiple complex cases are being handled simultaneously.

Although Choueiri’s day is often filled with administration and teaching—in addition to running his clinic—in the last year he also spearheaded multinational research aimed at identifying unique risk factors for COVID-19 in patients with cancer.

“Many of my mentors suggested that I always be dynamic and learn the next thing,” Choueiri recalled. “Learn it well, but today’s standard is not going to be tomorrow’s standard. You have to be agile, always.”

Always Doing Something

Time off tends to be infrequent for Choueiri, but the moments he does have away are spent on adventures with his wife, Sue, and their 2 children, aged 10 and 12 years. Traveling as a family is a favorite activity, as are skiing and cooking Lebanese food (as documented on Instagram). In addition, watching episodes of the Netflix series “Cobra Kai” with his son and competing in marathon Uno tournaments with his daughter are always cherished moments. Taking long walks with the newest member of the Choueiri family, Fergus, a soft-coated wheaten terrier who arrived just before Christmas in 2020, has also become a new and loved family pastime.

Often, his family time includes sporting events. Choueiri’s love for soccer and its international spirit is mirrored in his children, both of whom play in leagues. They are also season ticket holders for the New England Revolution, Boston’s Major League Soccer team, and spend lots of afternoons and evenings cheering on the Revs with friends. One of Choueiri’s favorite moments from the past year was when the team paid special tribute to health care heroes and he was among those honored during the COVID-19 pandemic.

And as a baseball fan, Choueiri makes sure to attend at least one Yankees vs Red Sox game when the rival teams play at Fenway. In terms of a dream sporting event, Choueiri has his sights set on the 2026 Fédération Internationale de Football Association (or FIFA) World Cup.

“It is taking part in the United States! That might be a time [when] I take 2 or 3 weeks completely off, rent a van with friends and family, and go all over the East Coast to watch the World Cup,” he mused. “That is a dream. I don’t have many things on my bucket list, but that is one of them.

”Regardless of the activity, Choueiri maintains that his time off must be done doing something.“

My mind is always on. I have to be doing something, not sitting on the beach or something,” he said. “I’m not the guy who can sit on the beach and just have a drink. That’s not me."

My Patients Are My Best Teachers

Something that combines Choueiri’s passion for medicine and sport is the Pan-Mass Challenge. Throughout his 4 years participating in the event, he has not only gotten more involved with the organization, but also helped grow the team to more than 20 people, including his brother-in-law.

They are Team More Cowbell, named for what Choueiri calls the best Saturday Night Livesketch of all time.

“It gives you perspective when you see your colleagues, when you see patients and their families, doing that ride and raising very important dollars for research,” Choueiri said of the event. “Who [were] my teachers to get me there? My patients. It is a life-changing experience to see people take the hurt, suffering, pain, and loss of cancer and transform it into a superhuman force for good and for hope. Participating in this event alongside them has changed my life.”

It was one of the first patients on the early cabozantinib trials, one who was initially given just 6 months to live and remains alive to this day, who first informed Choueiri of the race and persuaded him to get involved. The patient joked with him, telling Choueiri that his son was older and took part every year and that he should join as well. In very Choueiri fashion, he called the patient’s son for more information.

“My patients are my best teachers,” Choueiri said. “Being an oncologist is a privilege. Over the years, I have been blessed with many who are giving back by being patient advocates. Some, unfortunately, have lost their battle [with cancer], but others are able to live on because of research, clinical developments, and the will to continue, to persist, to fight, and to overcome.

“I am reminded every day that I walk into the Yawkey [Center for Cancer Care] and [Dana-Farber] buildings that life is about the journey—it’s about living in the present and being present. To witness the magnificence of what is possible when people dare to challenge convention, to commit themselves to a cause greater than themselves, and to work together for the betterment of community and humanity with whatever means they have because community and humanity are worth fighting for has been the gift of my lifetime, and I am so grateful.”