Cetuximab for the treatment of advanced bronchioloalveolar carcinoma (BAC): An Eastern Cooperative Oncology Group phase II study (ECOG 1504).

Abstract

7522 Background: Inhibitors of the epidermal growth factor receptor (EGFR) tyrosine kinase have demonstrated modest anticancer activity in pts with advanced BAC, a disease that is refractory to standard chemotherapy regimens. We conducted a phase II study to evaluate cetuximab, an antibody against EGFR, for the treatment of advanced BAC. Methods: Pts with advanced stage pure BAC or adenocarcinoma with BAC features, presence of measurable disease, 0 or 1 prior chemotherapy regimen, and ECOG performance status (PS) of 0-2 were eligible. Prior EGFR inhibitor therapy was not permitted. Cetuximab was given as a weekly i.v. infusion at 250 mg/m2 from week 2 onwards after an initial loading dose of 400 mg/m2 in week 1 until disease progression. The primary endpoint was determination of response rate. EGFR and KRAS mutations were evaluated by pyrosequencing. Results: 72 pts were enrolled and 68 met all eligibility criteria. Pt characteristics were: median age- 71 yrs, female– 57%; ECOG PS 0 or 1– 88%; no prior chemotherapy- 68%; and never smokers- 18%. Central pathology review confirmed the diagnosis in 45 out of 47 available specimens (mucinous- 35%; non-mucinous- 20%; Adeno with BAC features- 16%, pure BAC -29%). Approximately 50% of pts received more than 2 cycles of therapy (> 8 weeks). Skin rash was the most common toxicity (any grade 71%; grade 3- 15%) and hypomagnesemia was noted in 26%. The confirmed response rate was 6% and SD was observed in 37% of pts. The median survival was 13 m and the 1- and 2-year survival rates were 52% and 37% respectively. The median PFS was 3.2 m with a 6- months PFS rate of 22%. Tumor tissues were available from 55 pts for evaluation of EGFR and KRAS mutation status. Analysis of EGFR exon 20 polymorphisms demonstrate an allele frequency of Q787Q G = 0.55, A = 0.45; T790M, C = 1.0. Complete EGFR and KRAS mutation analysis will be presented at the meeting. Conclusions: The efficacy of cetuximab is comparable with that of EGFR TK inhibitors in the treatment of advanced BAC despite low response rates by RECIST. Supported in part by PHS Grants CA23318, CA66636, CA21115, CA21076 and from the NCI, NIH and the Department of Health and Human Services. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, ImClone Systems, Lilly ImClone Systems