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

BioNTech's statement on patent infringement lawsui…

BioNTech SE (Nasdaq: BNTX, "BioNTech") published an official statment: "BioNTech is aware of reports that Moderna has sued Pfizer and BioNTech, alleging that COMIRNATY® i...

Xenpozyme™ (olipudase alfa-rpcp) approved by FDA a…

The U.S. Food and Drug Administration (FDA) has approved Xenpozyme™ (olipudase alfa-rpcp) for the treatment of non-central nervous system (non-CNS) manifestations of acid...

FDA grants Breakthrough Therapy Designation to Pfi…

Pfizer Inc. (NYSE:PFE) today announced that its investigational Group B Streptococcus (GBS) vaccine candidate, GBS6 or PF-06760805, received Breakthrough Therapy Designat...

Malaria booster vaccine shows durable high efficac…

Researchers from the University of Oxford and their partners have today reported new findings from their Phase 2b trial following the administration of a booster dose of ...

Research reveals widespread use of ineffective COV…

Monoclonal antibodies are laboratory-designed treatments tailor-made to fight specific infections. In early 2021, the U.S. Food & Drug Administration issued emergency use...

Efficacy, cash and more will increase booster shot…

The more effective the COVID-19 booster, the more likely people are to get it, according to new Cornell research. And they are more likely to accept the booster shot with...

Strict COVID lockdowns in France improved cardiova…

A new paper in European Heart Journal - Digital Health, published by Oxford University Press, indicates that social-distancing measures like total lockdown have a measura...

U.S. clinical trial evaluating antiviral for monke…

A Phase 3 clinical trial evaluating the antiviral tecovirimat, also known as TPOXX, is now enrolling adults and children with monkeypox infection in the United States. St...

Stem cell-gene therapy shows promise in ALS safety…

Cedars-Sinai investigators have developed an investigational therapy using support cells and a protective protein that can be delivered past the blood-brain barrier. This...

Novartis invests in early technical development ca…

Novartis today announced it is investing in next-generation biotherapeutics with the creation of a fully integrated, dedicated USD 300m scientific environment that will b...

Drug turns cancer gene into "eat me" fla…

Tumor cells are notoriously good at evading the human immune system; they put up physical walls, wear disguises and handcuff the immune system with molecular tricks. Now...

Mucosal antibodies in the airways protect against …

High levels of mucosal antibodies in the airways reduce the risk of being infected by omicron, but many do not receive detectable antibodies in the airways despite three ...