Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, Inc. announced that the final analysis of the phase 3 NExUS (NSCLC research Experience Utilizing Sorafenib) trial evaluating Nexavar (sorafenib) tablets in patients with advanced non-squamous non-small cell lung cancer (NSCLC) showed that the study did not meet its primary endpoint of improving overall survival in the first-line setting.

NExUS evaluated Nexavar versus placebo in combination with two chemotherapeutic agents, gemcitabine and cisplatin. A positive secondary endpoint of progression-free survival (PFS) was observed in the trial. The safety and tolerability of the treatment triplet was as expected and did not show any new or unexpected toxicities. Data from this study are expected to be presented at an upcoming scientific meeting.

Nexavar is currently marketed worldwide for the treatment of hepatocellular carcinoma (HCC), or liver cancer, and advanced renal cell carcinoma (RCC), or kidney cancer.

Enrolment in NExUS commenced in February 2007. In 2008, based on the results seen in a previous Nexavar first-line NSCLC Phase 3 trial, the NExUS study protocol was amended to stop enrolling and treating squamous cell carcinoma patients. Of the squamous cell patients who were enrolled in the NExUS trial before the amendment, a higher mortality was observed. This finding was consistent with what was seen in the previous trial.

Bayer and Onyx will further review the findings of this analysis to determine what, if any, impact these data might have on other ongoing clinical trials evaluating the safety and efficacy of Nexavar.

"Bayer and Onyx are disappointed with these results, in particular, for patients who are suffering from this deadly disease," said Dr Dimitris Voliotis, vice president, global clinical development Oncology, Bayer HealthCare. "We are confident in our clinical trial program exploring Nexavar's potential in a variety of tumour types, including lung cancer. Based on encouraging data from a recently presented prospective biomarker trial and phase 2 signal-generating lung cancer studies, we believe it's critical to continue our evaluation of Nexavar in combination with targeted agents and as a monotherapy in later lines of treatment in lung cancer patients."

Nexavar is being evaluated by the companies and individual investigators in a variety of treatment settings for patients with non-small cell lung cancer, including a phase 3 monotherapy study in the third- and fourth-line setting and phase 2 studies in combination with other therapies in the second-line setting.

This phase 3, randomized, double-blind, placebo-controlled study evaluated Nexavar (sorafenib) tablets in combination with the chemotherapeutic agents, gemcitabine and cisplatin, in treatment-naïve non-small cell lung cancer patients. The primary endpoint was overall survival, and secondary endpoints included progression-free survival, tumour response and safety. Patients were randomized to receive 400 mg of oral Nexavar or matching placebo twice daily, in addition to gemcitabine and cisplatin for up to six cycles. Subsequently, patients continued in a maintenance phase where Nexavar or placebo was administered as a single agent. The study enrolled approximately 900 patients from sites throughout Europe, South America, Asia Pacific and the Middle East.

Nexavar, an oral anti-cancer therapy, is currently approved in more than 90 countries for liver cancer and in more than 95 countries for the treatment of patients with advanced kidney cancer. Nexavar inhibits both the tumour cell and tumour vasculature. In preclinical studies, Nexavar has been shown to inhibit members of two classes of kinases thought to be involved in both cell proliferation (growth) and angiogenesis (blood supply) - two important processes that enable cancer growth. These kinases included Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR B, KIT, FLT-3 and RET.

Nexavar is also being evaluated by the companies, international study groups, government agencies and individual investigators as a single agent or combination treatment in a wide range of cancers, including lung, thyroid, breast, ovarian and colorectal cancer and as an adjuvant therapy for liver and kidney cancer.