Targeted Therapy Combination Slows NSCLC

David Spigel, MD

Patients with refractory non-small cell lung cancer (NSCLC) had a statistically significant improvement in progression-free survival (PFS) when treated with targeted therapy duo versus a single agent, according to a study reported at the 2012 Chicago Multidisciplinary Symposium in Thoracic Oncology.

Patients treated with the combination of pazopanib and erlotinib had a median PFS of 2.6 months versus 1.8 months with erlotinib and placebo (hazard ratio [HR], 0.59; 95% CI, 0.43-0.83; P = .0016).

“Progression-free survival advantages with pazopanib and erlotinib were seen in several biomarker-defined subgroups,” said David Spigel, MD, lead author and director of Lung Cancer Research at the Sarah Cannon Research Institute in Nashville, Tennessee. “These results warrant additional study of pazopanib in non-small cell lung cancer.”

Pazopanib is an oral multikinase inhibitor approved for treatment of advanced renal cell carcinoma. A preliminary study demonstrated activity in NSCLC, as preoperative treatment with pazopanib was associated with a reduction in tumor size in 86% of patients with stage I-II NSCLC.¹ Additionally, the safety of combined treatment with pazopanib and erlotinib was demonstrated in a phase I clinical trial.²

Spigel reported findings from a randomized phase II trial involving 192 patients who had previously treated stage IIIB/IV NSCLC. Patients who had received one or two prior lines of therapy were eligible for the trial.

The patients were randomized 2:1 to pazopanib plus erlotinib or to erlotinib plus placebo. The primary endpoint was PFS, and key secondary endpoints included overall survival, objective response rate, and safety.

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The significant improvement did not translate into an overall survival advantage for patients treated with the combination of pazopanib and erlotinib. The combination arm had a median overall survival of 6.8 months compared with 6.7 months with erlotinib alone (HR 1.1; 95% CI, 0.77-1.55; P = .61).

The combination was associated with more grade 3 and higher treatment-emergent adverse events; grade 4 events were uncommon (4%).

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References

1. Altorki N, Lane ME, Bauer T, et al. Phase II proof-of-concept study of pazopanib monotherapy in treatment-naive patients with stage I/II resectable non—small-cell lung cancer. J Clin Oncol. 2010;28:3131-3137.
2. ClinicalTrials.gov. Available at: http://clinicaltrials.gov/ct2/show/NCT00619424?term=NCT00619424&rank=1.