New Standard of Care in Metastatic Clear-Cell Renal Cancer

Submitted by onc_editor on Tue, 12/19/2017 - 15:00

By Will Boggs MD

NEW YORK (Reuters Health) - The combination of ipilimumab and nivolumab replaces the previous standard of care for the first-line treatment of patients with intermediate- and poor-risk metastatic clear-cell renal cancer, according to updated European Association of Urology (EAU) guidelines.

The phase 3 Checkmate-214 trial showed superior survival with the ipilimumab-nivolumab (IN) combination, compared with the previous standard of care (sunitinib), prompting the update.

Dr. Thomas Powles from Queen Mary University of London, UK, and colleagues detail the new guidelines in their December 6 European Urology online report.

Because of its significant advantage for both response rates and overall survival, IN replaces cabozantinib, sunitinib, or pazopanib as the first choice for treating patients with intermediate- and poor-risk metastatic clear-cell renal carcinoma and becomes an alternate first-line therapy for patients with good-risk disease.

Based on weak evidence, the guidelines recommend offering a VEGF tyrosine kinase inhibitor as second-line therapy for IN-refractory patients.

The appropriate third-line treatment after IN and subsequent VEGF-targeted therapy remains unclear, although the panel recommends an agent that is approved in VEGF-refractory disease (only cabozantinib has shown a survival advantage in a phase 3 randomized trial).

“There is no evidence for sequencing of immune therapies, which remains within the realm of clinical trials,” the authors conclude. “Patients should only receive individual immune checkpoint inhibition once, in the opinion of the panel. Re-challenge with nivolumab or IN is not recommended at this stage. While data with the combination of VEGF-targeted therapy and immune checkpoint inhibition are promising, further randomized data will be needed before any recommendations can be provided.”

Dr. Robert A. Figlin from Cedars-Sinai Medical Center, Los Angeles, California, who has evaluated various treatments for metastatic renal cell carcinoma, told Reuters Health by email, "The addition of IN to the paradigm of previously untreated metastatic clear-cell renal cell carcinoma of intermediate and poor risk provides another step in the improvement of outcomes for these patients. There is nothing controversial, as long as the appropriate candidates for this treatment are chosen, risks and benefits are outlined, and patients with comorbid diseases that could be made worse by this treatment are excluded.”

“We have entered an era where immune-based therapies are the first treatment option for appropriately chosen patients, and with complete responses noted, improvement in overall survival compared to prior standards, and the possibility for durable remissions, this is now the standard,” he said.

Dr. Figlin added, “Unanswered questions remain: 1) how long should patients be treated to obtain this benefit? 2) how does this therapy affect good-prognosis patients? 3) is there a role for this approach in the adjuvant setting? 4) are there populations of patients who might benefit from another approach first (i.e., brain metastasis, bone metastasis patients, etc.)? and 5) how will this therapy compare to immune oncology approaches that are combined with a targeted therapy?”

Dr. Powles did not respond to a request for comment.


Eur Urol 2017.

(c) Copyright Thomson Reuters 2017. Click For Restrictions -