For the second time this year Bayer HealthCare Pharmaceuticals and Amgen’s Onyx Pharmaceuticals subsidiary have disclosed a late-stage clinical trial failure involving sorafenib (sold as Nexavar®), saying that a combination of sorafenib tablets plus capecitabine in patients with advanced breast cancer did not meet its primary endpoint of improving progression-free survival (PFS).

Bayer and Amgen furnished no data detailing how far the sorafenib-capecitabine combo missed the mark compared with placebo, saying that detailed efficacy and safety analyses from the trial “are expected to be presented at an upcoming scientific congress.”

The combination was assessed in the Phase III Trial Comparing Capecitabine in Combination with SorafenIb or Placebo for Treatment of Locally Advanced or MetastatIc HER2–Negative Breast Cancer (RESILIENCE). The randomized, double-blind, placebo-controlled Phase III study enrolled 537 patients in more than 20 countries, including the U.S., Europe, Japan and Australia.

Patients were randomized to receive 600 mg of oral sorafenib or matching placebo daily on a continuous schedule, in addition to 1000mg/m2 of capecitabine twice daily for 14 days of a 21 day cycle.

RESILIENCE evaluated sorafenib in combination with capecitabine in patients with locally advanced or metastatic HER2 negative breast cancer who are resistant to or have failed prior taxane, and are resistant to or have failed an anthracycline or for whom further anthracycline therapy is not indicated. Secondary endpoints for the trial included overall survival, time to progression, overall response rate, disease control rate, duration of response, patient reported quality of life and safety.

Based on an initial review of data, bayer and Amgen said, the types of adverse events observed were generally comparable with those known for either sorafenib or capecitabine individually.

The failure of RESILIENCE was the second Phase III setback for Bayer and Amgen this year in clinical studies toward supporting additional indications for sorafenib. The treatment is approved in the U.S. for patients with unresectable heptocellular carcinoma (HCC), the most common form of liver cancer – as well as patients with advanced renal cell cancer and patients with locally recurrent or metastatic, progressive, differentiated thyroid cancer refractory to radioactive iodine treatment.

Back in March, the companies said that their pivotal Sorafenib as Adjuvant Treatment in the Prevention of Recurrence of Hepatocellular Carcinoma (STORM) trial did not meet its primary endpoint of improving recurrence-free survival. The trial included approximately 1,100 patients who were randomized to receive 400 mg of sorafenib twice daily or matching placebo for four years or until disease recurrence, whichever occurred first. Secondary endpoints included time to recurrence of HCC (intrahepatic and extrahepatic) and overall survival.  Safety and tolerability were also assessed.

The companies said they continue to study sorafenib as a potential treatment for a variety of other forms of cancer.

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