Novartis announced that results of a global phase III study showed that Afinitor (everolimus) did not extend overall survival compared to placebo in patients with locally advanced or metastatic hepatocellular carcinoma (HCC) after progression on or intolerance to sorafenib. Hepatocellular carcinoma, an aggressive and debilitating cancer, is the most common type of liver cancer. Novartis will not proceed with regulatory filings of Afinitor in this indication.

"While we are disappointed with these results, Novartis remains committed to studying everolimus through a robust research and development programme to address unmet needs in different types of cancer," said Alessandro Riva, Global Head, Oncology Development & Medical Affairs, Novartis Oncology. "To date, Afinitor has proven efficacy in a number of tumour types, including hormone receptor positive advanced breast cancer, advanced pancreatic neuroendocrine tumors and advanced renal cell carcinoma."

The results of the HCC trial do not impact the worldwide approvals of Afinitor for these other indications. Everolimus is also in phase III development in other diseases, including gastrointestinal and lung neuroendocrine tumors (NET), HER2 positive breast cancer, lymphoma and tuberous sclerosis complex (TSC). Results of these trials are expected during 2014 and 2015.

The phase III study, EVOLVE-1 (EVerOlimus for LiVer cancer Evaluation-1), is a randomized, double-blind, placebo-controlled trial examining the efficacy and safety of everolimus versus placebo, plus best supportive care (BSC), in adult patients with advanced HCC whose disease progressed after treatment with or who were intolerant to sorafenib, a targeted therapy. The study results continue to be evaluated and will be presented at an upcoming medical conference.

EVOLVE-1 involved 546 patients and was conducted at 156 sites worldwide. Patients in the trial were randomized (2:1) to receive therapy with everolimus 7.5 mg/day orally plus BSC or placebo plus BSC. The primary endpoint was overall survival. Secondary endpoints included time to tumor progression, disease control rate,time to deterioration of performance status, safety and quality of life.

Afinitor (everolimus) tablets is approved in more than 100 countries, including the United States and throughout the European Union, in the oncology settings of advanced renal cell carcinoma following progression on or after vascular endothelial growth factor (VEGF)-targeted therapy, and in the United States and European Union for locally advanced, metastatic or unresectable progressive neuroendocrine tumors of pancreatic origin.

Everolimus is approved as Afinitor in the European Union for the treatment of hormone receptor-positive, HER2 negative (HR+/HER2 negative) advanced breast cancer, in combination with exemestane, in postmenopausal women without symptomatic visceral disease after recurrence or progression following a non-steroidal aromatase inhibitor. In the United States, Afinitor is approved for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2 negative breast cancer (advanced HR+/HER2 negative breast cancer) in combination with exemestane after failure of treatment with letrozole or anastrozole.

Everolimus is also available from Novartis for use in certain non-oncology patient populations under the brand names Afinitor or Votubia, Certican and Zortress and is exclusively licensed to Abbott and sublicensed to Boston Scientific for use in drug-eluting stents.

Indications vary by country and not all indications are available in every country. The safety and efficacy profile of everolimus has not yet been established outside the approved indications. Because of the uncertainty of clinical trials, there is no guarantee that everolimus will become commercially available for additional indications anywhere else in the world.