Continuation of afatinib beyond progression: Results of a randomized, open-label, phase III trial of afatinib plus paclitaxel (P) versus investigator’s choice chemotherapy (CT) in patients (pts) with metastatic non-small cell lung cancer (NSCLC) progressed on erlotinib/gefitinib (E/G) and afatinib—LUX-Lung 5 (LL5).

Lung Cancer - Non-Small Cell Metastatic
Session Type and Session Title: 
Poster Highlights Session, Lung Cancer - Non-small Cell Metastatic
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 8019^)
Martin H. Schuler, Chih-Hsin Yang, Keunchil Park, Jaafar Bennouna, Yuh-Min Chen, Christos Chouaid, Filippo De Marinis, Ji Feng Feng, Francesco Grossi, Dong-Wan Kim, Xiaoqing Liu, Shun Lu, Janos Strausz, Yurii Vinnyk, Rainer Wiewrodt, Caicun Zhou, Vikram K. Chand, Bushi Wang, Joo-Hang Kim, David Planchard, for the LUX-Lung 5 Investigators; West German Cancer Center, University Duisburg-Essen, Essen, Germany; National Taiwan University, Taipei, Taiwan; Samsung Medical Center, Seoul, South Korea; Institut de Cancerologie de l’Ouest, Nantes, France; Division of Thoracic Oncology, Department of Chest Medicine, Taipei Veterans General Hospital & Department of Medicine, National Yang-Ming University, Taipei, Taiwan; CHI Creteil, Creteil, France; 1st Oncological Pulmonary Unit, San Camillo, High Specialization Hospital, Rome; and European Institute of Oncology, Milano, Italy; Jiangsu Province Cancer Hospital, Nanjing, China; National Institure for Cancer Research, Genoa, Italy; Seoul National University Hospital, Seoul, South Korea; Affiliated Hospital of Academy of Military Medical Science, Beijing, China; Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China; Koranyi National Institute for Pulmonology, Budapest, Hungary; Kharkiv Regional Clinical Oncology Center, Kharkiv, Ukraine; University Hospital Muenster, Muenster, Germany; Tongji University Medical School Cancer Institute, Shanghai, China; Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT; Yonsei University College of Medicine, Seoul, South Korea; Gustave Roussy, Villejuif, France

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: Improved disease control with continuation of EGFR inhibition beyond progression has been suggested in retrospective/non-randomized studies, however, this has yet to be prospectively evaluated in a randomized trial. LL5 is a randomized trial, which assessed the efficacy of continuation of the irreversible ErbB family blocker, afatinib (A), beyond progression with the addition of P in NSCLC pts with prior benefit from reversible EGFR tyrosine kinase inhibitors (E/G) and A. Methods: In this open-label, global phase III trial, pts with NSCLC who had failed ≥1 line of CT and E/G (after ≥12 wks treatment) were treated with A (50 mg/day) in Part A (n=1154). Upon progression, those with ≥12 wks on A were eligible to be randomized 2:1 to A+P (40 mg/day; 80 mg/m2/week) or single agent investigator’s choice CT in Part B. Primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), and safety. Results: 202 pts were randomized (A+P, n=134; CT, n=68) and baseline characteristics were well balanced (median age 60 yrs, females 49%, ECOG PS 0–1 91% overall). A statistically significant improvement in PFS was observed on A + P vs CT arm (median 5.6 vs 2.8 months, hazard ratio (HR) 0.60 (95% CI 0.43, 0.85; p=0.003). ORR was also significantly higher in A+P arm vs CT (32.1% vs 13.2%; p=0.005). OS was similar in both arms 12.2 vs. 12.2 months, HR 1.00 (95% CI 0.70, 1.43; p=0.994). Most common related adverse events (AEs) with A+P vs CT were diarrhea (53.8% vs 6.7%), alopecia (32.6% vs 15.0%) and asthenia (27.3% vs 28.3%). Conclusions: ContinuedErbB family blockade with A with the addition of P significantly improved PFS and ORR vs CT alone in heavily pretreated pts with acquired resistance to E/G and progression on A monotherapy. AEs were considered manageable. Our data support that tumors progressing on E/G and A continue to depend on signalling through the receptors of the ErbB family and can benefit from continuous ErbB family blockade with A. Clinical trial information: NCT01085136.