New Combination Drug Treatment Helps Some People With Stage 4 Kidney Cancer

MSK patient Michael Szczerbienski

Thanks to a clinical trial for stage 4 kidney cancer, Michael Szczerbienski’s cancer is still in remission more than three years after treatment.

Michael Szczerbienski had always been blessed with good health, so the day he found blood in his urine, he was quite alarmed. His doctor sent him for a CT scan, which revealed a tumor on his left kidney. Michael, whose kidney cancer was already advanced, went to Memorial Sloan Kettering Cancer Center (MSK), where he had surgery and then was given the chance to join a clinical trial of a drug combination that had never been tested before. Thanks to that trial, Michael’s cancer is still in remission more than three years later.

Michael, now 68, says “When you’re a patient at MSK, the people who are treating you are the best there is, hands down.”

Results of this first-of-its kind clinical trial were published in the May 11, 2023, issue of the New England Journal of Medicine (NEJM). Michael’s medical oncologist, MSK kidney cancer expert Robert Motzer, MD, was co-corresponding and senior author of the study.

The trial showed that adding a targeted therapy to a standard combination for stage 4 kidney cancer was more effective than giving the standard treatment alone. About 87% of patients getting the new combination saw their tumors shrink or stabilize, compared with 55% of those getting the standard treatment. Additionally, the average time it took for the disease to progress was 16.9 months in the experimental group compared with 11.3 months in the other group. However, there were significant side effects.

The targeted therapy tested was cabozantinib (Cabometyx®), which is already approved to treat kidney cancer either on its own or in combination with the immunotherapy drug nivolumab (Opdivo®). This study compared the addition of cabozantinib to nivolumab combined with another immunotherapy drug, ipilimumab (Yervoy®), to the immunotherapy combination plus a placebo. The two-immunotherapy combination also is currently a standard treatment for advanced kidney cancer.

Clinical Trial for Stage 4 Kidney Cancer Adds Targeted Therapy to Immunotherapy

The trial, an international phase 3 study, enrolled more than 850 patients, all of whom had stage 4 kidney cancer and had not yet received any drug treatments. Some of them had previously had surgery, including Michael, whose tumor was removed by MSK urologic surgeon Paul Russo, MD. After the surgery, Dr. Russo determined that Michael needed additional treatment due the aggressiveness of his cancer. Dr. Russo referred Michael to Dr. Motzer, who was able to offer Michael access to the clinical trial.

“When I started in the trial, I remember praying to God that I was in the group that got the extra drug and not the placebo,” Michael says. Although all the results from the study have not been unblinded yet, Dr. Motzer is certain that Michael was in the cabozantinib group based on the side effects he experienced that were likely related to the targeted therapy.

Studying the Side Effects of New Kidney Cancer Drug Treatments

The treatment side effects for Michael included pain and severe swelling of his legs. He was worried. Overall, 45% of people in the experimental group had reactions that were severe enough they had to stop treatment early, compared with 24% of those who got the older standard combination. The most common side effects seen in the trial were liver problems, skin problems, and gastrointestinal issues like diarrhea.

Dr. Robert Motzer

Dr. Robert Motzer has led the development of many new treatments for kidney cancer over the past 15 years.

Michael was one of the patients who had to stop taking the drugs before the end of the trial. He is grateful that he was able to receive the treatment long enough to put his cancer into remission.

“Because of the severity of the side effects, it’s too early to determine whether this new combination will become a standard treatment,” Dr. Motzer explains. “Longer follow-up is needed to see if patients will live longer following treatment with the addition of the targeted drug compared to the standard immunotherapy program. Future research will focus on determining who is most likely to benefit from the addition of cabozantinib.”

MSK Treats Michael’s Kidney Cancer After It Spreads to his Brain

About two years after Michael finished his treatment on the clinical trial, he began feeling like he was in a mental fog. Eventually he started losing control of the left side of his body. An MRI showed that his kidney cancer had spread to an isolated spot on the right side of his brain. In May 2022, MSK neurologic surgeon Cameron Brennan performed surgery to remove the tumor.

“When I had my kidney surgery with Dr. Russo, I wasn’t scared, but with this operation on my brain, I was truly scared,” Michael remembers. “Dr. Brennan was absolutely fantastic. He explained everything to me so well, and he said, ‘You’re going to be fine.’ And that helped me tremendously.”

Michael also needed follow-up radiation treatments to his brain, which he was able to get at MSK-Monmouth near his home in New Jersey.

Recovery after the brain surgery and radiation treatments was difficult. Michael leaned on many care providers at MSK, especially physical therapist Lauren Moore, also at MSK-Monmouth. Eventually, he started feeling like himself again.

Michael Is Doing Well After Clinical Trial for Kidney Cancer

Today Michael, who retired in 2020 from a job in finance, remains cancer free. He enjoys taking walks with his wife, going to his favorite Italian restaurant on the New Jersey shore, and dining out in Manhattan with his two adult sons. This year he has several trips planned, including to his two favorite vacation spots: Williamsburg, Virginia, and Nantucket, Massachusetts.

“Words cannot express how I feel about MSK. Every person I met helped to make a crappy situation into something bearable,” Michael says. “And Dr. Motzer was the maestro of this whole journey. He took care of me every step of the way.”

This research was supported by Exelixis, the company that makes cabozantinib. Bristol Myers Squibb provided nivolumab and ipilimumab. Toni Choueiri, the study’s first and co-corresponding author, is supported in part by the Dana–Farber/Harvard Cancer Center Kidney Specialized Program of Research Excellence (2P50CA101942-16) and Program 5P30CA006516-56, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, Pan Mass Challenge, Hinda and Arthur Marcus, and Loker Pinard Funds for Kidney Cancer Research at the Dana–Farber Cancer Institute. Patients treated at MSK were supported in part by National Institutes of Health grant P30 CA008748.

Dr. Motzer has relationships with or financial interests in Aveo, Clinical Care Options, Eisai, Evicore, Merck & Co Inc., PeerView Institute for Medical Education (PVI), Research to Practice, Takeda Pharmaceuticals, Targeted Oncology, Total CME, and WebMD.