Major developments in kidney cancer in 2021

2021 was a bumper year for kidney cancer developments, including several new treatment approvals by the FDA and a much better understanding of how kidney cancer is impacted by COVID-19 infections and vaccines.

“All are very important topics that are affecting patients as we speak,” said Nancy Moldawer, RN, of Cedars-Sinai Medical Center in Los Angeles, Ca, and a member of the KCA’s Clinical Advisory Board. “Between deciding what first line therapy to chose from to the concern of the genetic risk of renal cell carcinoma, are all very real concerns to patients.”

We rounded up the major developments in kidney cancer this year, focusing on those with the greatest impact or potential impact for people facing kidney cancer.

New drug approvals or new regimen approvals

• Pembrolizumab (Keytruda) was approved for treating renal cell carcinoma (RCC) patients who are at risk of disease recurrence after a nephrectomy or after a nephrectomy and removal of other metastatic lesions). Read more.

• Belzutifan (Welireg) was approved as the first-ever treatment for people with RCC (and other tumor types) associated with Von Hippel-Lindau (VHL) disease. Read more.

• Lenvatinib (Lenvima) plus pembrolizumab was approved for first-line treatment in advanced RCC. Read more.

• Tivozanib (Fotivda) was approved for adults with relapsed or refractory advanced RCC after they’ve received two or more prior systemic therapies. Read more.

• Nivolumab (Opdivo) plus cabozantanib (Cabometyx) was approved as first-line treatment in advanced RCC. Read more.

“Scientifically, I think the belzutifan [approval] is most important. It’s the only agent for which there’s truly a new target,” said Dr. Walter Stadler, a medical oncologist at the University of Chicago Medical Center, though he noted researchers don’t know how useful it will be for people with non-VHL-related tumors. Belzutifan targets and inhibits the hypoxia-inducible factor-2 alpha (HIF-2α) protein, which is involved in regulating cellular oxygen levels, a pathway that VHL disease and related cancers can be sensitive to.

“We should be closely watching how the belzutifan story develops as it is tested as monotherapy and in other clinical combinations,” said Dr. Chung-Han Lee, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York.

Both Lee and Stadler noted adjuvant pembrolizumab was an important development and one to monitor. When data from the phase III KEYNOTE-564 trial, on which the FDA approval was based, was presented at ASCO 2021, lead researcher Dr. Toni Choueiri of the Dana-Farber Cancer Center in Boston said the results could make pembrolizumab a potential new standard of care after nephrectomy. However, Stadler said the current evidence showing improved disease-free survival in some patients but not improved overall survival still makes adjuvant treatment a controversial choice.

“It will benefit a few people to delay recurrence,” Stadler said. “The real question is, does it matter if I treat in an adjuvant, or preventive, manner versus treating only those patients who recur? If the ultimate survival for the cancer is the same, why expose people to toxic therapy now?”

Lee flagged the CANTATA and PAPMET trials, both with results presented in the past year, as deserving mention. CANTATA was a disappointment in that the glutaminase inhibitor telaglenastat did not improve patient outcomes. Telaglenastat may have represented a new approach to kidney cancer treatment but Lee said the compound and glutaminase inhibition are still paths to explore for kidney cancer. Thephase II PAPMET trial showed benefits with cabozantinib for metastatic papillary RCC, a rare subtype that didn’t have effective treatment options. This regimen is now part of the National Comprehensive Cancer Network’s guidelines for treating papillary RCC.

“The rate of improvement [in patient care] is rapidly accelerating, not only with novel combinations and new drug classes, but also new disease states in which treatment is helpful,” said Dr. Chung-Han Lee.

According to Dr. Tian Zhang, a medical oncologist at UT Southwestern Medical Center, both the adjuvant pembrolizumab and belzutifan approvals “represents a direct result from National Cancer Institute and pharmaceutical resources, scientific advances, cancer researchers, and patients who have generously participated in clinical trials. Scientific discoveries in understanding the biology of kidney cancer are directly translating into new treatment options for our patients.”

When looking to the future, Zhang said ongoing trials in first-line kidney cancer that address treatment sequencing approaches and combination trials in the perioperative or adjuvant setting will be areas to watch.

Stadler included belzutifan in non-VHL clear cell RCC settings, survival outcomes over several years with adjuvant pembrolizumab, triplet therapy and whether it is worth the increased toxicity, and long-term survival with immunotherapy as well as discontinuing immunotherapy (especially the ipilimumab/nivolumab combination) in that list. The latter in particular, he said, would help answer the question of whether researchers are getting closer to a cure for some patients.

Covid-19 vaccines are safe and effective for people with cancer

A number of studies, many of which were presented during the 2021 Congress of the European Society for Medical Oncology (ESMO), showed people with cancer – including kidney cancer – have appropriate immune response to COVID-19 vaccination and that vaccination is safe in these patients, even those who are undergoing treatment with chemotherapy and/or immunotherapy. Read more.

Consensus statement on genetic risk assessment for inherited RCC answers who should get genetic risk assessment and what types of tests they should get

In late 2019, a group of 33 researchers, healthcare providers, and advocates with expertise in hereditary RCC came together to determine how to care for patients with suspicion of an inherited form of kidney cancer. Though the resulting guidelines, published in the August 2021 edition of the journal Cancer, may not account for all the scenarios where a genetic risk assessment would be useful, the group attempted to clarify for whom, when, and how genetic risk assessment should be performed. Read the guidelines.

There was strong agreement for the following issues:

• Who should undergo genetic risk assessment?
  • People with certain kidney tumors (papillary type 1, chromophobe, renal angiomyolipomas and clear cell RCC) in both kidneys or multiple tumors in one kidney 
  • People with hybrid renal tumors (oncocytomas/chromophobe), SDH-tumors, or FH-deficient tumors
  • People with more than 1 of the following tumors outside the kidney:  pheochromocytoma or paraganglioma, endolymphatic sac tumor, uveal melanoma, and FH-deficient uterine fibroid
  • Certain people with 1^st and/or 2^nd degree relatives with RCC or features suggestive of an inherited cancer syndrome. 
• What type of genetic testing should be performed and how?
  • Anyone undergoing testing should have pre-test counseling by someone with expertise in inherited cancer syndromes either in-person or by telemedicine.
  • If there are signs of a specific condition, only that gene should be tested, otherwise a test of multiple genes should be done in those with more general risk factors.
  • Single gene testing by blood is also preferred following the finding of a mutation in the tumor itself in order to check for it being an inherited form or when pretest counseling cannot be done.

Dr. Christopher G. Wood, chair of the KCA’s Board of Directors, dies

Dr. Christopher G. Wood, a urologic surgeon at MD Anderson Cancer Center in Houston, Texas and Chair of the KCA’s Board of Directors, died on November 3, 2021 after an unexplained neurologic condition. The outpouring of grief, support, memories, and gratitude for his gifts as a surgeon and mentor showed how pivotal Dr. Wood was to the kidney cancer community. During a memorial at the 2021 IKCS: North America in Austin, Texas immediately after Dr. Wood died, his friend and fellow KCA board member Dr. Bradley Leibovich said: “Chris was an unbelievably dedicated, superb surgeon who was always striving for excellence in the operating room… because Chris cared about his patients deeply. His compassion for people was truly remarkable. He was absolutely dedicated to being the best he could possibly be at all points in time in service of his patients.”

Within the KCA, Dr. Wood was a force nearly since its inception in the early 1990s, helping to shape it into the international awareness, advocacy, and support organization it is today. The KCA’s Dr. Christopher G. Wood Endowment will help continue his life’s work in kidney cancer as a clinician, researcher, educator, and mentor. Learn more and contribute.