| General information |
| Database: | DB00959 |
| Objective: | Bevacizumab and erlotinib have been shown to improve survival in stage IV non small cell lung cancer (non small cell lung cancer). Thisphase I/II trial was designed to incorporate these agents with induction and concurrent chemoradiotherapy in stage III non small cell lung cancer. |
| Authors: | Socinski MA, et al |
| Title: | Incorporating bevacizumab and erlotinib in the combinedmodality treatment of stage III non small cell lung cancer: results of a phase I/II trial. |
| Journal: | J Clin Oncol. |
| Year: | 2012 |
| PMID: | 23045594 |
| Trial Design |
| Clinical Trial Id: | NCT00280150 |
| Agent: | bevacizumab erlotinib
|
| Target: | NA
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | stage III non small cell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | bevacizumab+erlotinib |
| Study Type: | phase I/II trial |
| Key Patients Feature: | pts of stage III non small cell lung cancer |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | no erlotinib, versus cohorts 2 and 3 received erlotinib at 100 and 150 mg |
| Treatment Info: | Patients 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. |
| Primary End Point: | ORR, PFS, toxicity |
| Secondary End Point: | NA |
| Patients Number: | 45 |
| Trial Results |
| DLT_MTD: | DLTs exceeding the prespecified definitions occurred in cohort 3. The DLTs included one episode each of grade 3 interstitial pneumonitis attributed to erlotinib and PH attributed to bevacizumab in a patient with squamous histology. Cohort 2 (erlotinib dose of 100 mg) was then selected for the phase II portion of the trial. |
| Objective Response Rate: | 39% (95% CI, 24% to 55%) |
| Disease Control Rate: | 60% (95% CI, 44% to 75%) |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 10.2 months (95% CI, 8.4 to 18.3 months) |
| Median OS A vs. C: | 18.4 months (95% CI, 13.4 to 31.7 months) |
| Adverse Event(agent arm): | The principal toxicity was esophagitis (29% grade 3 or 4 esophagitis, with one patient with grade 3 tracheoesophageal fistula), which was often prolonged. |
| Conclusions: | The 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. |