Novartis study of Afinitor® in advanced liver cancer does not meet primary endpoint of overall survival

NovartisNovartis has 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[1]. Hepatocellular carcinoma, an aggressive and debilitating cancer, is the most common type of liver cancer[2].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 program 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 tumor 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.

Study details
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[3]. 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[1][3].

About everolimus
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.

About Novartis
Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2012, the Group achieved net sales of USD 56.7 billion, while R&D throughout the Group amounted to approximately USD 9.3 billion (USD 9.1 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 131,000 full-time-equivalent associates and operate in more than 140 countries around the world.

1. Data on file.
2. Faloppi L. et al. Evolving strategies for the treatment of hepatocellular carcinoma: from clinical-guided to molecularly-tailored therapeutic options. Cancer Treat Rev. 2011; 37(3):169-77.
3. US National Institutes of Health. Global Study Looking at the Combination of RAD001 Plus Best Supportive Care (BSC) and Placebo Plus BSC to Treat Patients With Advanced Hepatocellular Carcinoma (EVOLVE-1). Available at http://clinicaltrials.gov/ct2/show/NCT01035229?term=EVOLVE-1&rank=1. Accessed August 2013.

Most Popular Now

Cannabis extract helps reset brain function in psy…

Research from King's College London has found that a single dose of the cannabis extract cannabidiol can help reduce brain function abnormalities seen in people with psyc...

For first time in 40 years, cure for acute leukemi…

Acute myeloid leukemia is one of the most aggressive cancers. While other cancers have benefitted from new treatments, there has been no encouraging news for most leukemi...

Consuming milk at breakfast lowers blood glucose t…

A change in breakfast routine may provide benefits for the management of type 2 diabetes, according to a new study published in the Journal of Dairy Science. H. Douglas G...

New cancer treatment uses enzymes to boost immune …

Researchers at The University of Texas at Austin have developed a new approach to treating cancer using enzyme therapy. The enzyme, PEG-KYNase, does not directly kill can...

Bayer accelerates six new startups

Changing the experience of health: that's the focus of the six startups which the Bayer G4A team has included in the Accelerator program this year. The young companies fr...

Novartis receives European Commission approval of …

Novartis today announced that the European Commission (EC) has approved Kymriah® (tisagenlecleucel, formerly CTL019). The approved indications are for the treatment of pe...

Shire completes sale of oncology franchise

Shire plc (LSE: SHP, NASDAQ: SHPG) announces today that it has completed the sale of its Oncology franchise to Servier S.A.S. for $2.4 billion. The franchise includes the...

Bristol-Myers Squibb - Pfizer Alliance ACROPOLIS™ …

The Bristol-Myers Squibb-Pfizer Alliance will present 15 Eliquis® (apixaban) posters at the ESC Congress 2018 held in Munich, Germany, August 25-29, 2018. Nine of the pos...

Antioxidant reduces risk for second heart attack, …

Doctors have long known that in the months after a heart attack or stroke, patients are more likely to have another attack or stroke. Now, a paper in the Journal of the A...

SOLAR-1 trial of Novartis investigational alpha-sp…

Novartis today announced the global Phase III SOLAR-1 trial evaluating the investigational alpha-specific PI3K inhibitor BYL719 (alpelisib) has met the primary endpoint s...

Novartis to divest the Sandoz US dermatology busin…

Novartis today announced it has agreed to sell selected portions of its Sandoz US portfolio, specifically the Sandoz US dermatology business and generic US oral solids po...

New tablet production facility in Ingelheim: Cente…

Boehringer Ingelheim held a groundbreaking ceremony for the construction of a new production facility for innovative drugs. This new Solids Launch facility will focus on ...