Phase I/II trial of bevacizumab (B) and erlotinib (E) with induction (IND) and concurrent (CON) carboplatin (Cb)/paclitaxel (P) and 74 Gy of thoracic conformal radiotherapy (TCRT) in stage III non-small cell lung cancer (NSCLC).

Abstract

7016 Background: Agents which target the epidermal growth factor receptor (EGFR) and inhibit angiogenesis have been shown to improve overall survival (OS) in advanced NSCLC and have radiosensitizing properties Methods: Patients (pts) received Cb (AUC=6), P (225 mg/m2) and B (15 mg/kg) on days 1 and 22. On day 43 patients received Cb (AUC=2) and P (45 mg/m2) weekly x 7 weeks (wks) with TCRT to 74 Gy; cohort 1 (n=5) received B 10 mg/kg q 2 wks, cohort 2 (n=5) and cohort 3 (n=5) both received B 10 mg/kg q 2 wks as well E at 100 mg and 150 mg Tuesday-Friday each week of concurrent therapy. After completion of concurrent therapy pts received consolidation therapy (CT) with B+ E for 6 cycles. All histologies were eligible; an early stopping rule for pulmonary hemorrhage (PH) was included for the squamous (SQ) pts. The primary end-point was 1-year progression free survival (PFS). Results: 45 patients eligible patients were accrued; median age 61 yrs (range 34 to 74), 33 non-SQ and 12 SQ; 29 stage IIIA and 16 stage IIIB; 33 pts PS 0 and 12 PS of 1. Cohort 2 was expanded to the phase II trial. CT was determined to not be feasible and SQ cohort was closed due to PH. Grade ≥ 3 toxicity observed with IND therapy was neutropenia (42%) and grade 3 hypertension (2%). Grade ≥ 3 toxicities observed with CON were esophagitis (29%), pneumonitis (2%); neutropenia (13%), hgb (7%), thrombocytopenia (7%); one trachoesphogeal fistula was observed. In SQ cohort 3 of 12 patients experienced PH; 1 grade 3, 2 grade 5. 33 pts have experienced disease progression or death; the 1-year PFS rate observed was 44% (95% CI, 29-58%), median PFS was 10 months (95% CI, 8-22). 27 pts have died, and the median follow-up for survivors is 37 months (range 5-54); median OS was 19 months (95% CI, 13 to 33). The median OS observed in the non-SQ and SQ cohorts was 19 and 17 months, respectively. Conclusions: The PFS and OS with the addition of B+E to CbP with 74 Gy TCRT appears similar to previous experience with CbP alone with 74 Gy TCRT.