FRONTIERS IN PHARMACOLOGY
Sequential treatment with pazopanib and everolimus yields a median overall survival exceeding 2 years in predominantly older and sicker patients with metastatic renal cell carcinoma (RCC) treated in real-world settings, according to results of an Italian multicenter cohort study.
“These data confirmed that pazopanib was effective, even in reduced dosing, and well tolerated and suggested that everolimus may represent an opportunity to continue a therapy when patients cannot further tolerate angiogenesis inhibitors or develop a resistance,” wrote Sabrina Rossetti, MD, of the Istituto Nazionale Tumori Fondazione G. Pascale, Naples, and associates ( Front Pharmacol. 2017 Jul 20;8:484 ).
“Overall, the sequential therapy showed favorable clinical outcomes and a good safety profile and may be feasible even for elderly patients or with multiple comorbidities,” they said.
The investigators prospectively enrolled 31 consecutive patients with newly diagnosed metastatic RCC. They had a median age of 68 years. Fully 73.3% underwent nephrectomy before treatment; 87.1% had at least one comorbidity, and 25.8% had at least three of them.
All patients were treated with the antiangiogenic tyrosine kinase inhibitor pazopanib (Votrient) as first-line therapy and, after disease progression on that agent or discontinuation for toxicity, with the mTOR inhibitor everolimus (Afinitor) as second-line therapy.
The median overall survival with the two-drug sequence was 26.5 months. Median progression-free survival was 10.6 months with pazopanib and 5.3 months with everolimus.
Patients were able to continue on pazopanib for a median time of 8.1 months, with 31% requiring dose reduction. They were able to continue on everolimus for a median time of 4.4 months, with 16% requiring dose reduction.
Main adverse events of any grade on pazopanib were hypertension (48.4%), fatigue (32.2%), and thyroid disorders (19.3%). Those on everolimus were anemia (32.2%), hypercholesterolemia (22.6%), and hyperglycemia (22.6%).
“The choice of second-line treatment in the new therapeutic paradigm is dramatically changed with the approval of new drugs, such as nivolumab and cabozantinib,” noted Dr. Rossetti and colleagues. “The next step in optimizing mRCC management would be the identification of new prognostic and predictive factors to detect a personalized sequence for each patient.”
