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Bevacizumab/erlotinib combined therapy associated with substantial risk of esophageal toxicity
Researchers cannot recommend bevacizumab and erlotinib as a combined modality therapy for patients with stage III non–small cell lung cancer because of a lack of an efficacy signal and the significant risk of esophageal toxicity.
Mark A. Socinski, MD, director of the lung cancer section at the University of Pittsburgh Medical Cancer Center, and colleagues enrolled 45 patients with NSCLC in this phase 1/2 trial. Median patient age was 61 years. Roughly half of the participants were men, and 64% had stage IIIA disease.
Mark A. Socinski
Patients underwent induction chemotherapy, which consisted of carboplatin plus bevacizumab. In all, 40 patients started thoracic conformal radiation therapy (TCRT) on day 43. Of those, 34 patients completed TCRT to a dose of 74 Gy.
During phase 1, researchers divided patients into three cohorts. Patients in cohort 1 received no erlotinib, patients in cohort 2 received erlotinib at 100 mg, and patients in cohort 3 received 150 mg from Tuesday through Friday during TCRT. The 6 weeks of consolidation therapy was planned to start 3 to 6 weeks later, and it was to consist of 150 mg of erlotinib daily and 15 mg/kg of bevacizumab (Avastin, Genentech) every 3 weeks.
The objective response rates to induction were 39% (95% CI, 24%-55%) and overall treatment were 60% (95% CI, 44%-75%). Median PFS was 10.2 months (95% CI, 8.4-18.3 months), and median OS was 18.4 months (95% CI, 13.4-31.7 months).
The most common toxicity was esophagitis, which was often prolonged. Twenty-nine percent of patients had grade 3 or 4 esophagitis, and one patient had a grade 3 tracheoesophageal fistula. As a result, consolidation therapy with bevacizumab and erlotinib was not possible.
“The tantalizing promise of breakthrough results from their über-aggressive approach failed to materialize, leaving in its wake worrisome adverse effects that prevented the administration of all intended therapy without meaningful clinical gains and an underwhelming overall survival of 18.4 months,” David Ruben, MD, and Paul A. Bunn, MD, of the University of Colorado School of Medicine, wrote in an accompanying editorial.
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