Nexavar® (sorafenib) appears to significantly delay disease progression and provide a trend toward improved overall survival among patients with heavily pre-treated non–small cell lung cancer (NSCLC). These results were from a Phase II intergroup study with a randomized discontinuation design. Results were reported at the 2008 annual meeting of the American Society of Clinical Oncology (ASCO).

Nexavar is considered to provide cytostatic properties, and as such, stabilization of disease is an important endpoint of studies evaluating these types of agents. Ultimately, the hope is that improved overall survival will be achieved through halting cancer progression with cytostatic agents; if so, various forms of cancers can be treated as more of a chronic illness, while some patients may derive greater benefit from standard therapies with the addition of agents such as Nexavar. Nexavar continues to demonstrate promise in some types of cancers, and research is continuing in the evaluation of Nexavar in different phases of treatment and stages of cancers.

Researchers from the University of Texas Southwestern Medical Center in Dallas, Texas, recently conducted a trial with a randomized discontinuation design to evaluate the effectiveness of Nexavar in the treatment of NSCLC patients who had received extensive prior chemotherapy. The trial included 342 patients whose disease had progressed following at least two prior chemotherapy regimens.

All patients received induction therapy with Nexavar. Those who experienced responses to Nexavar remained on the drug until disease progression, while those who experienced disease stabilization on the drug were randomized to continued treatment with Nexavar (n=51) or placebo (n=32). Lead author of the study, Dr. Schiller stated, “The strategy is based on the hypothesis that patients with rapidly progressive disease may not stay on the drug long enough to derive a benefit,” and furthermore, “The strategy also enriches for patients with slower-progressing disease, who might be more likely to benefit.”

Eighty-three patients were eligible for the randomization portion of the trial; they were assessed two months following randomization. Patients who derived benefit from Nexavar remained on the drug, while those who progressed went off-study. Patients in the placebo arm who progressed were crossed over to receive Nexavar. The primary objective of the study was disease stabilization or response at two months following randomization. Secondary objectives included median survival, progression-free survival, and overall response rates.

• Disease stabilization at two months following randomization was 47% for patients randomized to Nexavar and 19% of patients randomized to placebo (P=0.01).
• Median progression-free survival was 3.6 months for those who received Nexavar compared with two months for those who received placebo (HR=2.16 for placebo group, P=0.009).
• Median overall survival was nearly one year (11.9 months) for those treated with Nexavar compared with nine months for those who received placebo (HR=1.50 for placebo group, P=0.18).
• Grade 4 cerebrovascular ischemia occurred in four patients, grade 5 pulmonary hemorrhage and renal failure occurred in one patient each, and fatigue and hand-foot reactions were the most common grade 3 toxicities.

Comments: These researchers concluded that Nexavar has single-agent activity that provides clinical benefit in heavily pre-treated patients with NSCLC. Additional studies are warranted to further evaluate Nexavar.

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Reference: Schiller JH, et al. A randomized discontinuation phase II study of sorafenib versus placebo in patients with non-small cell lung cancer who have failed at least two prior chemotherapy regimens: E2501. ASCO Meeting 2008; Abstract 8014.