For patients diagnosed with metastatic papillary kidney cancer, a rare subtype of kidney cancer with few effective treatment options, the outlook has historically been grim. There were no well-established treatments for metastatic papillary renal cell carcinoma (pRCC), and studies had found the average survival after diagnosis to be only around eight months.
A SWOG clinical trial called S1500, also known as PAPMET, set out to change that.
Mutations in the MET gene are a hallmark of papillary kidney cancer, and researchers have been investigating drugs that target this pathway. The S1500 trial enrolled 147 patients across 65 centers in the U.S. and Canada and randomly assigned them to one of four treatments: sunitinib (the then-standard of care, which targets a different pathway), or one of three drugs targeting MET – cabozantinib, crizotinib, or savolitinib.
Findings: Cabozantinib significantly prolonged progression-free survival compared to sunitinib, with patients on cabozantinib going a median of 9.0 months before their cancer progressed versus 5.6 months on sunitinib. The objective response rate (the proportion of patients whose tumors meaningfully shrank) was also considerably higher with cabozantinib at 23%, compared to just 4% with sunitinib. The other two MET-targeting drugs, crizotinib and savolitinib, did not outperform sunitinib and their study arms were closed early. The results immediately changed the standard of care for metastatic papillary kidney cancer.
The story behind the science: For us, this result is as much about the research as it is about what made it possible: a culture of mentorship and long-term investment. The story began in 2009, when the trial’s lead investigator, Dr. Sumanta Pal, was a fellow at City of Hope with dreams of building a career in kidney cancer research. Through SWOG’s Young Investigator Training Course, he found mentors, funding, including a Coltman Fellowship from The Hope Foundation for Cancer Research, and professional collaborators who became close colleagues.
As Dr. Pal reflected, “Academic medicine can feel lonely, but SWOG brings you together with some of the best experts in your field to work on trials. You can do studies at SWOG where you have a big impact on the design and also get substantial peer review. The science is extremely well-vetted. And you can study a rare cancer treatment because SWOG can enroll patients through a national network.”
The S1500 story illustrates how SWOG’s combination of scientific infrastructure, national reach, and investment in the next generation of researchers can produce results that change care for patients. If you can spare five more minutes, watch this inspiring interview with S1500 participant and now-SWOG patient advocate, Laura Esfeller!
