Scientists on an international multi-institutional trial found a significantly more effective drug to treat patients with metastatic papillary kidney cancer than the current standard of care. Papillary kidney cancer forms in cells that line the small tubes of the kidney that filter waste from the blood and make urine.

Primo “Lucky” Lara, Jr., cancer center director, helped author a drug comparison trial, setting a new standard of care for rare kidney cancer.
Primo “Lucky” Lara, Jr., cancer center director, helped author a drug comparison trial, setting a new standard of care for rare kidney cancer.

Cabozantinib, a small molecule inhibitor, showed better survival results than the current standard treatment Sunitinib. Two other competing cancer drugs were no better than Sunitinib. The findings from the trial, published Feb. 13 in The Lancet, are expected to change the standard of care for advanced papillary kidney cancer.

Previous research found that the average survival rate for patients with this type of cancer was eight months after diagnosis.

“There are currently no effective treatments for metastatic papillary kidney cancer,” said Primo “Lucky” Lara, Jr., director of the UC Davis Comprehensive Cancer Center and senior author on the paper. “The remarkable results from this study bring hope to patients with this rare form of kidney cancer.”

Collaborative research leads to enhanced outcomes for patients

The study, called S1500 (PAPMET), is a randomized clinical trial led by Sumanta Pal, a clinical professor of medical oncology at the City of Hope and an investigator at the SWOG Cancer Research Network, which designed and managed the trial. SWOG is a national clinical trials collaborative supported by the National Cancer Institute (NCI) and is part of its National Clinical Trials Network, the nation’s largest and oldest cancer trials network. 

Lara was Pal’s mentor as part of SWOG’s Young Investigator Training Course and served as senior mentor in the planning, development, and conduct of S1500. Lara is deputy chair of SWOG.

“It was my absolute honor to contribute to this important clinical trial,” said Lara.

Researchers from 65 centers studied 147 patients with papillary kidney cancer, most of whom had not received any prior treatment. Patients were randomly assigned to one of four treatment groups: those who took sunitinib (a receptor tyrosine inhibitor and the current standard treatment) and those who took cabozantinib, crizotinib or savolitinib (drugs targeting mutation in the MET gene, a hallmark of  metastatic papillary kidney cancer).

The team wanted to see how long it would take the cancer to spread or return, a measure known as progression-free survival. They found that patients receiving sunitinib went a median of 5.6 months before their cancer progressed; patients receiving savolitinib and crizotinib fared much worse overall. But cabozantinib gave patients a median of 9.2 months before their cancer progressed.

In addition, 23% of patients had a significant reduction in the size of their tumor with cabozantinib. In contrast, only 4% of patients saw this kind of tumor response with sunitinib.

“The magnitude of the response was surprising,” Pal said. “We still have a long way to go to help make patients’ lives longer and better, but we do have a new standard treatment for these rare cancer patients.”

S1500 was sponsored by the NCI and funded by National Institutes of Health (NIH) through NCI grants CA180888, CA180819, CA180820, CA180821, CA180863 and CA180868.

Co-authors on this study are Catherine Tangen and Melissa Plets of the SWOG Statistics and Data Management Center, Ian M. Thompson, Jr., of CHRISTUS Santa Rosa, Naomi BalzerHaas of Abramson Cancer Center, Daniel J. George of Duke University Medical Center, Daniel Heng of Tom Baker Cancer Center, Brian Shuch of Institute of Urologic Oncology at UCLA, Mark Stein of Columbia University, Maria Tretiakova of University of Washington, Peter Humphrey and Adebowale Adeniran of Yale University; Vivek Narayan of Abramson Cancer Center, Georg Bjarnason of Sunnybrook Odette Cancer Centre, Ulka Vaishampayan of Wayne State University and University of Michigan; Ajjai Alva of University of Michigan, Tian Zhang of Duke Cancer Research Institute, Scott Cole of Oklahoma Cancer Specialists and Research Institute and John Wright of National Cancer Institute. 

Findings from this study were presented at the American Society of Clinical Oncology virtual 2021 Genitourinary Cancers Symposium on Saturday, Feb. 13, 2021.