Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): A phase 2B, open-label, randomised controlled trial

The Lancet Oncology

Volumn 17, Issue 5, 2016, Pages 577-589

  Park, Keunchil ^a   Tan, Eng Huat ^b   O'Byrne, Ken ^c   Zhang, Li ^d   Boyer, Michael ^e   Mok, Tony ^f   Hirsh, Vera ^g   Yang, James Chih Hsin ^h   Lee, Ki Hyeong ⁱ   Lu, Shun ^j   Shi, Yuankai ^k,l   Kim, Sang We ^m   Laskin, Janessa ⁿ   Kim, Dong Wan ^o   Arvis, Catherine Dubos ^p   Kölbeck, Karl ^q   Laurie, Scott A ^r   Tsai, Chun Ming ^s   Shahidi, Mehdi ^t   Kim, Miyoung ^u   Massey, Dan ^t   Zazulina, Victoria ^t   Paz Ares, Luis ^v   more..

^a Sungkyunkwan University School of Medicine   (South Korea)

^b DIVISION OF MEDICAL ONCOLOGY   (Singapore)

^c QUEENSLAND UNIVERSITY OF TECHNOLOGY   (Australia)

^d SUN YAT SEN UNIVERSITY CANCER CENTER   (China)

^e Chris O'Brien Lifehouse   (Australia)

^f CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

^g MCGILL UNIVERSITY   (Canada)

^h NATIONAL TAIWAN UNIVERSITY HOSPITAL   (Taiwan)

ⁱ Chungbuk National University Hospital   (South Korea)

^j SHANGHAI CHEST HOSPITAL   (China)

^k CANCER HOSPITAL   (China)

^l Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs   (China)

^m Asan Medical Center   (South Korea)

ⁿ BRITISH COLUMBIA CANCER AGENCY   (Canada)

^o Seoul National University Hospital   (South Korea)

^p CENTRE FRANÇOIS BACLESSE   (France)

^q KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^r OTTAWA REGIONAL CANCER CENTRE   (Canada)

^s NATIONAL YANG MING UNIVERSITY   (Taiwan)

^t BOEHRINGER INGELHEIM LTD   (United Kingdom)

^u BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

^v HOSPITAL UNIVERSITARIO 12 DE OCTUBRE   (Spain)

more..

Author keywords

[No Author keywords available]

Indexed keywords

AFATINIB; ALANINE AMINOTRANSFERASE; ARGININE; ASPARTATE AMINOTRANSFERASE; BICARBONATE; CREATININE; EPIDERMAL GROWTH FACTOR RECEPTOR; GEFITINIB; LEUCINE; LIVER ENZYME; EGFR PROTEIN, HUMAN; PROTEIN KINASE INHIBITOR; QUINAZOLINE DERIVATIVE;

ACIDOSIS; ACNE; ACUTE KIDNEY FAILURE; ACUTE RESPIRATORY FAILURE; ADULT; ADVERSE DRUG REACTION; AGED; ALOPECIA; ANUS DISEASE; ARTICLE; BACTERIAL SKIN DISEASE; BICARBONATE BLOOD LEVEL; BONE MARROW DEPRESSION; BRAIN ISCHEMIA; BRAIN METASTASIS; CANCER CHEMOTHERAPY; CANCER GROWTH; CANCER PATIENT; CANCER STAGING; CANCER SURVIVAL; CHEMOTHERAPY INDUCED EMESIS; CONFUSION; CONJUNCTIVITIS; CONTROLLED STUDY; DECREASED APPETITE; DEHYDRATION; DIARRHEA; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ERUPTION; DRUG FATALITY; DRUG SAFETY; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; DRY NOSE; DRY SKIN; EGFR GENE; ENCEPHALOMYELITIS; EXON; EXPLORATORY RESEARCH; FATIGUE; FEMALE; FOLLOW UP; GASTROINTESTINAL PAIN; GENE DELETION; GENE MUTATION; HAND FOOT SYNDROME; HUMAN; HUMAN CELL; HUMAN TISSUE; HYPOALBUMINEMIA; HYPOKALEMIA; INTERSTITIAL LUNG DISEASE; INTERTRIGO; KIDNEY FAILURE; LIVER FAILURE; MAJOR CLINICAL STUDY; MALE; MALIGNANT NEOPLASTIC DISEASE; MUCOSA INFLAMMATION; MULTICENTER STUDY; NAUSEA; NEUTROPENIA; NON SMALL CELL LUNG CANCER; OPEN STUDY; OVERALL SURVIVAL; PARONYCHIA; PHASE 2 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; RASH; RESPIRATORY DISTRESS; SIDE EFFECT; STOMATITIS; SURVIVAL TIME; TOXIC HEPATITIS; TREATMENT RESPONSE; WEIGHT REDUCTION; CARCINOMA, NON-SMALL-CELL LUNG; CLASSIFICATION; CLINICAL TRIAL; DISEASE FREE SURVIVAL; GENETICS; KAPLAN MEIER METHOD; MIDDLE AGED; MUTATION; PATHOLOGY; PATHOPHYSIOLOGY; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; CARCINOMA, NON-SMALL-CELL LUNG; DISEASE-FREE SURVIVAL; DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS; FEMALE; HUMANS; KAPLAN-MEIER ESTIMATE; MALE; MIDDLE AGED; MUTATION; PROTEIN KINASE INHIBITORS; QUINAZOLINES; RECEPTOR, EPIDERMAL GROWTH FACTOR;

EID: 84964389363     PISSN: 14702045     EISSN: 14745488     Source Type: Journal    
DOI: 10.1016/S1470-2045(16)30033-X     Document Type: Article

References (33)

1. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004, 350:2129-2139.
2. Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004, 304:1497-1500.
3. Sharma SV, Bell DW, Settleman J, Haber DA Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 2007, 7:169-181.
4. Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010, 362:2380-2388.
5. Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010, 11:121-128.
6. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009, 361:947-957.
7. Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2012, 13:239-246.
8. Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 2013, 31:3327-3334.
9. Wu YL, Zhou C, Hu CP, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol 2014, 15:213-222.
10. Wu YL, Zhou C, Liam CK, et al. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol 2015, 26:1883-1939.
11. Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2011, 12:735-742.
12. Haaland B, Tan PS, de Castro G, Lopes G Meta-analysis of first-line therapies in advanced non-small-cell lung cancer harboring EGFR-activating mutations 8. J Thorac Oncol 2014, 9:805-811.
13. Haspinger ER, Agustoni F, Torri V, et al. Is there evidence for different effects among EGFR-TKIs? Systematic review and meta-analysis of EGFR tyrosine kinase inhibitors (TKIs) versus chemotherapy as first-line treatment for patients harboring EGFR mutations. Crit Rev Oncol Hematol 2015, 94:213-227.
14. Popat S, Mok T, Yang JC, et al. Afatinib in the treatment of EGFR mutation-positive NSCLC--a network meta-analysis. Lung Cancer 2014, 85:230-238.
15. Li D, Ambrogio L, Shimamura T, et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene 2008, 27:4702-4711.
16. Solca F, Dahl G, Zoephel A, et al. Target binding properties and cellular activity of afatinib (BIBW 2992), an irreversible ErbB family blocker. J Pharmacol Exp Ther 2012, 343:342-350.
17. Andersen PK, Hansen MG, Klein JP Regression analysis of restricted mean survival time based on pseudo-observations. Lifetime Data Anal 2004, 10:335-350.
18. Shuster JJ Median follow-up in clinical trials. J Clin Oncol 1991, 9:191-192.
19. Yonesaka K, Kudo K, Nishida S, et al. The pan-HER family tyrosine kinase inhibitor afatinib overcomes HER3 ligand heregulin-mediated resistance to EGFR inhibitors in non-small cell lung cancer. Oncotarget 2015, 6:33602-33611.
20. Yu HA, Arcila ME, Rekhtman N, et al. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res 2013, 19:2240-2247.
21. Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007, 316:1039-1043.
22. Katakami N, Atagi S, Goto K, et al. LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. J Clin Oncol 2013, 31:3335-3341.
23. Miller VA, Hirsh V, Cadranel J, et al. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol 2012, 13:528-538.
24. Schuler M, Yang JC, Park K, et al. Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial. Ann Oncol 2015, 27:417-423.
25. Douillard JY, Ostoros G, Cobo M, et al. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br J Cancer 2014, 110:55-62.
26. Fukuoka M, Wu YL, Thongprasert S, et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol 2011, 29:2866-2874.
27. Kuan FC, Kuo LT, Chen MC, et al. Overall survival benefits of first-line EGFR tyrosine kinase inhibitors in EGFR-mutated non-small-cell lung cancers: a systematic review and meta-analysis. Br J Cancer 2015, 113:1519-1528.
28. Yang JC, Wu YL, Schuler M, et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol 2015, 16:141-151.
29. Lee CK, Wu YL, Ding PN, et al. Impact of specific epidermal growth factor receptor (EGFR) mutations and clinical characteristics on outcomes after treatment with EGFR tyrosine kinase inhibitors versus chemotherapy in EGFR-mutant lung cancer: a meta-analysis. J Clin Oncol 2015, 33:1958-1965.
30. Janne PA, Yang JC, Kim DW, et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med 2015, 372:1689-1699.
31. Park K, Lee JS, Lee KH, et al. Updated safety and efficacy results from phase I/II study of HM61713 in patients (pts) with EGFR mutation positive non-small cell lung cancer (NSCLC) who failed previous EGFR-tyrosine kinase inhibitor (TKI). Proc Soc Am Clin Oncol 2015, 33. abstr 8084.
32. Sequist LV, Soria JC, Goldman JW, et al. Rociletinib in EGFR-mutated non-small-cell lung cancer. N Engl J Med 2015, 372:1700-1709.
33. Wu SG, Liu YN, Tsai MF, et al. The mechanism of acquired resistance to irreversible EGFR tyrosine kinase inhibitor-afatinib in lung adenocarcinoma patients. Oncotarget 2016, published online Feb 4. 10.18632/oncotarget.7189.