A phase II study of BIBW 2992 in patients with adenocarcinoma of the lung and activating EGFR mutations (LUX-Lung 2).
Authors: C. Yang, J. Shih, W. Su, T. Hsia, C. Tsai, S. I. Ou, R. Calvo, X. J. Cong, M. Shahidi, V. A. Miller
Journal: Journal of Clinical Oncology (2010)

7521^ Background: NSCLC patients whose tumors harbor epidermal growth factor receptor EGFR/HER1 mutations represent a unique subpopulation with unparalleled responsiveness to EGFR tyrosine kinase inhibitors. A phase II study of BIBW 2992 – an oral, novel, potent irreversible inhibitor of EGFR and human HER2 – has completed accrual in Taiwan and the US. Methods: Patients with a stage IIIB/IV lung adenocarcinoma, EGFR mutations in exons 18–21 (by direct sequencing), chemo-naïve or with progressive disease following first-line cytotoxic chemotherapy, measurable disease, and ECOG PS 0–2 received 50 mg or 40 mg BIBW 2992 qd until progression. Response was assessed at 4, 8 and 12 weeks, and at 8-weekly intervals thereafter; images were centrally reviewed. Analysis included primary endpoint objective response rate (ORR) and secondary endpoint progression-free survival (PFS). Results: 444 patients were tested for EGFR mutations and 129 received treatment. Tumor size reduction was seen in 90% of patients. ORR and disease control rate (DCR) was 62% and 94%, respectively, for del19; 52% and 85% for L858R; and 43% and 78% for other mutations based on investigator assessment. L858R mutation was seen in 54 (42%), del19 in 52 (40%) and other mutations in 23 (18%) patients. Median PFS was estimated to be 12 months (95% CI: 10–19.2) for the overall group, 12 months (95% CI: 10–19.2) in del19, 16.3 months (95% CI:10–Inf) in L858R, and 15.6 months (95% CI:10–19.2) when combined. The most common drug-related adverse events (AEs) were diarrhea and rash/acne, as reported in 95% of patients each and were Grade 3 in 18% and 19% of patients, respectively. No Grade 4 cases were reported for these events. Conclusions: Administration of BIBW 2992 resulted in a high ORR, DCR and PFS in NSCLC patients with EGFR mutations. Gastrointestinal and skin disorders were the most frequently observed AEs and were manageable with adequate supportive care and dose reduction. Updated response and PFS data based on independent imaging review will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Boehringer Ingelheim Boehringer Ingelheim In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519-521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2010 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest.