Incorporating Bevacizumab and Erlotinib in the Combined-Modality Treatment of Stage III Non-Small-Cell Lung Cancer: Results of a Phase I/II Trial.

Socinski MA, Stinchcombe TE, Moore DT, Gettinger SN, Decker RH, Petty WJ, Blackstock AW, Schwartz G, Lankford S, Khandani A, Morris DE.

Source

Mark A. Socinski, Thomas E. Stinchcombe, Dominic T. Moore, Amir Khandani, and David E. Morris, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill; W. Jeffrey Petty and A. William Blackstock, Wake Forest University, Winston-Salem; Garry Schwartz and Scott Lankford, Carolinas Medical Center-Northeast, Concord, NC; and Scott N. Gettinger and Roy H. Decker, Yale University School of Medicine, New Haven, CT.

Abstract

PURPOSEBevacizumab and erlotinib have been shown to improve survival in stage IV non-small-cell lung cancer (NSCLC). This phase I/II trial was designed to incorporate these agents with induction and concurrent chemoradiotherapy in stage III NSCLC. PATIENTS AND METHODSPatients received induction chemotherapy (carboplatin area under the curve [AUC] 6, paclitaxel 225 mg/m(2), and bevacizumab 15 mg/kg on days 1 and 22) followed by concurrent chemotherapy (carboplatin AUC 2 and paclitaxel 45 mg/m(2) weekly with bevacizumab 10 mg/kg every other week for four doses) and thoracic conformal radiation therapy (TCRT) to 74 Gy. In the phase I portion, cohort 1 received no erlotinib, whereas cohorts 2 and 3 received erlotinib at 100 and 150 mg, respectively, Tuesday through Friday, during TCRT. Consolidation therapy with erlotinib (150 mg daily) and bevacizumab (15 mg/kg every 3 weeks) was planned 3 to 6 weeks later for six cycles.ResultsForty-five eligible patients were enrolled. The objective response rates to induction and overall treatment were 39% (95% CI, 24% to 55%) and 60% (95% CI, 44% to 75%), respectively. The median progression-free and overall survival times were 10.2 months (95% CI, 8.4 to 18.3 months) and 18.4 months (95% CI, 13.4 to 31.7 months), respectively. The principal toxicity was esophagitis (29% grade 3 or 4 esophagitis, with one patient with grade 3 tracheoesophageal fistula), which was often prolonged. Consolidation therapy with bevacizumab and erlotinib was not feasible. CONCLUSIONThe use of bevacizumab and erlotinib as administered in this trial is not recommended given the lack of an efficacy signal and the substantial risk of esophageal toxicity.

TimAllenMDJD

Wednesday, October 10, 2012