- Exelixis Inc. on Tuesday unveiled detailed results from a Phase 3 study of cabozantinib, showing the drug improved median overall survival by just over 2 months versus placebo in previously treated patients with a common type of liver cancer.
- That improvement translated into a 24% reduction in relative risk, a benefit that the biotech believes will support approval of cabozantinib to treat advanced hepatocelullar carcinoma (HCC). Exelixis plans to file with the Food and Drug Administration for a label expansion sometime this quarter.
- Yet, a higher number of patient deaths in the treatment arm could raise some questions around the drug's safety. Shares in the biotech dropped by more than 7% Wednesday on the data.
Exelixis already markets cabozantinib as Cabometyx for patients with advanced renal cell carcinoma (RCC), a type of kidney cancer, and as Cometriq for metastatic medullary thyroid cancer. Together, sales of the two brands accounted for just over $96 million in the third quarter, up 12% from a year prior.
In 2018, Exelixis plans to build on that foundation by expanding into previously untreated RCC patients and into the new indication of HCC. The biotech already secured U.S. approval on the former in mid December, roughly two months ahead of the FDA's target decision date. Now, with positive data in hand in HCC, a filing in HCC will soon follow.
Success on both fronts would help cabozantinib compete with other tyrosine kinase inhibitors like Novartis AG's Votrient (pazopanib), Pfizer Inc.'s Sutent (sunitinib) and Bayer AG's Nexavar (sorafenib).
Exelixis' study of cabozantinib in HCC compared the drug to placebo on overall survival in second- or third-line patients. In October, an independent data monitoring committee recommended the trial, called CELESTIAL, be stopped early due to efficacy.
Detailed results, which were disclosed Tuesday, showed patients who received cabozantinib lived a median of 10.2 months, compared to 8 months for those on placebo. Median progression-free survival in the treatment arm more than doubled the mark seen in the placebo group.
CELESTIAL was primarily focused on proving cabozantinib's benefit as a second-line option following treatment with Nexavar. A subgroup analysis could help support that positioning, showing longer overall survival in patients who had only previously received Nexavar (a group representing 70% of the total patients enrolled in CELESTIAL).
But that efficacy came with some safety concerns. Six patients in the treatment arm died, compared to only one in the placebo group. Patients in the study were randomized 2:1 to either treatment or placebo, meaning there were more patients on treatment. Still, the higher number of deaths — each due to a different treatment-related proximate cause — could raise questions on safety.
In total, 467 patients were randomized to the treatment arm and 237 enrolled in the placebo arm — putting the percentage patients who died in each arm at 1.28% and 0.42%, respectively.
Patients receiving cabozantinib also had more frequent swelling of the hands and feet, hypertension and higher liver enzyme levels. Sixteen percent of patients on the drug discontinued treatment due to adverse events, versus 3% on placebo.
Advanced HCC has a particularly poor prognosis, elevating the need for the new treatments to help patients who have failed first-line treatments.
Editor's note: This article has been updated to include numbers of patients randomized to each treatment arm.