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Multicenter, Randomized, Phase II Trial of CI-1033, an Irreversible Pan-ERBB Inhibitor, for Previously Treated Advanced Non–Small-Cell Lung Cancer

Pasi A. Jänne, Joachim von Pawel, Roger B. Cohen, Lucio Crino, Charles A. Butts, Steven S. Olson, Irene A. Eiseman, Alberto A. Chiappori, Beow Y. Yeap, Peter F. Lenehan, Kathy Dasse, Meredith Sheeran, Philip D. Bonomi

From the Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital; Department of Medicine, Massachusetts General Hospital, Boston, MA; Asklepios Fachklinik Fuer Lungenkrankheiten, Gauting, Germany; Fox Chase Cancer Center, Philadelphia, PA; Ospedale Silvestrini, Perugia, Italy; Cross Cancer Institute, Edmonton, Alberta, Canada; Pfizer Global Research & Development, Ann Arbor, MI; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; and Rush Cancer Institute, Section of Oncology, Chicago, IL

Address reprint requests to Pasi A. Jänne, MD, PhD, Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana Farber Cancer Institute, 820A, 44 Binney St, Boston, MA 02115; e-mail: pjanne{at}partners.org

Purpose: To evaluate the efficacy of the pan-ERBB inhibitor, CI-1033, in platinum-refractory or recurrent advanced-stage non–small-cell lung cancer (NSCLC).

Patients and Methods: This open-label, randomized phase II trial evaluated CI-1033 in patients with advanced-stage NSCLC who experienced treatment failure after or were refractory to platinum-based chemotherapy. Three oral CI-1033 doses were evaluated in 21-day dosing cycles: 50 mg daily for 21 consecutive days, 150 mg daily for 21 consecutive days, and 450 mg daily for 14 consecutive days followed by 7 days of no treatment. The primary efficacy end point was the 1-year survival rate.

Results: One hundred sixty-six patients were randomly assigned to treatment. Baseline patient demographics were well balanced. The most common drug-related adverse events were rash and diarrhea. The 450-mg arm (14 days on/7 days off) was closed early due to an excessive rate of adverse events. The 1-year survival rates were 29%, 26%, and 29%, respectively, in the three arms. The response rates were 2%, 2%, and 4%, and stable disease was confirmed in 16%, 23%, and 18% of patients, respectively, in the three study arms. Exploratory analyses demonstrated a prolonged survival in patients who developed a rash and in those with baseline tumor ERBB-2 expression.

Conclusion: CI-1033 had modest activity in unselected NSCLC patients but did not meet its primary end point. Future studies should focus on identifying methods of patient selection.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.