New studies of two drugs, showing that each works better than the standard treatment for advanced kidney cancer, should lead to changes in patient care, researchers said on Friday. The pharmaceutical giant based in the US said this past July the study had been stopped earlier than scheduled due to the drug being more effective than Afinitor an established product made by Novartis, but the trial’s detailed results did not become disclosed until Saturday in Vienna at the European Cancer Congress.
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Asked whether her study or the one reported by Choueiri offered a suggestion of improved 5-year survival, Sharma said the comparatively brief follow-up precluded any comments beyond speculation.
A drug that unleashes the immune system to attack tumors, an approach pioneered by a Houston scientist, extends the lives of patients with advanced kidney cancer, according to an global trial expected to lead to regulatory approval. Advanced kidney patients have a survival rate between 41% and 8%.
“We have a real opportunity to change clinical practice for patients when other therapies have failed”, said principal investigator Padmanee Sharma, MD, PhD, professor, Departments of Genitourinary Medical Oncology and Immunology and scientific director of the Immunotherapy Platform, part of the University of Texas MD Anderson Cancer Center’s Moon Shots Program.
The benefit from both treatments compared with Afinitor “is unequivocal, ” according to an editorial in the New England Journal of Medicine, where both studies were published. Seven-two percent of patients in the overall study population had previously been treated with 1 angiogenesis inhibitor for advanced RCC.
In the Phase 3 CheckMate -025 trial, Opdivo demonstrated a median overall survival (OS) benefit of 25 months compared to 19.6 months for everolimus.
“Cabozantinib is a new drug that targets possible escape mechanisms of tumor cells, including the tyrosine kinases MET, VEGFR, and AXL”, Choueiri explained. Cabozantinib [Cometriq] is a salvage treatment for patients whose tumors progress during VEGF therapy, however, without a significant overall survival benefit and with significant side effects…it will not precede nivolumab in the therapeutic sequence. The median duration of treatment was 5.5 months with nivolumab and 3.7 months with everolimus.
The open-label, parallel assignment CheckMate-025 trial randomized 821 previously treated patients with advanced or metastatic clear-cell RCC in a 1:1 ratio to 3 mg/kg of IV nivolumab every 2 weeks or 10 mg of oral everolimus daily until progression or unacceptable toxicity. “If it is caught early, the prognosis is good; 81% of patients with stage I disease, in which the tumour is confined to the kidney, survive for at least five years”. That sets the drug up to be used beyond lung cancer and melanoma. The most common grade 3/4 AEs with cabozantinib were hypertension (15%), diarrhea (11%), and fatigue (9%) versus anemia (16%), fatigue (7%), and hyperglycemia (5%) with everolimus. Such patients are then usually given everolimus.
The FDA recently granted nivolumab a breakthrough therapy designation for the treatment of patients with advanced RCC, which will expedite the development and regulatory review of the anti-PD-1 agent in this setting.
AstraZeneca, Roche and other drugmakers are also developing similar drugs known as PD-L1 inhibitors.
Nivolumab was initially approved in December 2014 for patients with unresectable or metastatic melanoma following treatment with ipilimumab (Yervoy) or a BRAF inhibitor. Cabozantinib is sold in capsules for thyroid cancer, but was made into tablets of different dosages for the kidney cancer study.
Because the drugs are already approved, doctors can legally prescribe them for any condition.
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Kidney cancer is the eighth most common cancer in the United Kingdom and survival rates plummet if it is caught late. The drugs are expensive: a year’s treatment with Opdivo can cost $150,000.
