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Efficacy and Safety Results of the Afatinib Expanded Access Program

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      Afatinib is an oral, irreversible ErbB family blocker approved for first-line treatment of metastatic epidermal growth factor receptor ( EGFR) mutation–positive non–small cell lung cancer (NSCLC). The expanded access program (EAP) allowed early access to afatinib and provided additional data on its safety, tolerability, and efficacy.


      The afatinib EAP was an open-label, multicenter, single-arm program in the United States that treated and followed patients with locally advanced or metastatic NSCLC harboring EGFR mutations. Afatinib 40 mg was administered orally once daily until discontinuation due to disease progression, adverse events (AEs), or transition to commercially available drug.


      Three hundred twenty-two patients received ≥1 dose of afatinib. Most patients had received prior therapies. Drug-related AEs occurred in 89.4% of patients, including 7.8% with serious AEs. The most common afatinib-related AEs (all grades) were diarrhea (77.0%) and rash (36.0%). Dose reductions occurred in 31.1% of patients. Discontinuation rates due to diarrhea (1.6%) or rash/acne (0.3%) were low. Efficacy data were collected and analyzed when available, with 17.1% and 69.9% of patients achieving objective response and disease control, respectively, in this highly pretreated population.


      No additional or unexpected safety concerns were revealed, and afatinib demonstrated antitumor activity in a heavily pretreated NSCLC patient population in a routine clinical setting.

      Trial Registration Identifier: NCT01649284.


      Boehringer Ingelheim Pharmaceuticals, Inc.

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      Most cited references 5

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      Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations.

      The LUX-Lung 3 study investigated the efficacy of chemotherapy compared with afatinib, a selective, orally bioavailable ErbB family blocker that irreversibly blocks signaling from epidermal growth factor receptor (EGFR/ErbB1), human epidermal growth factor receptor 2 (HER2/ErbB2), and ErbB4 and has wide-spectrum preclinical activity against EGFR mutations. A phase II study of afatinib in EGFR mutation-positive lung adenocarcinoma demonstrated high response rates and progression-free survival (PFS). In this phase III study, eligible patients with stage IIIB/IV lung adenocarcinoma were screened for EGFR mutations. Mutation-positive patients were stratified by mutation type (exon 19 deletion, L858R, or other) and race (Asian or non-Asian) before two-to-one random assignment to 40 mg afatinib per day or up to six cycles of cisplatin plus pemetrexed chemotherapy at standard doses every 21 days. The primary end point was PFS by independent review. Secondary end points included tumor response, overall survival, adverse events, and patient-reported outcomes (PROs). A total of 1,269 patients were screened, and 345 were randomly assigned to treatment. Median PFS was 11.1 months for afatinib and 6.9 months for chemotherapy (hazard ratio [HR], 0.58; 95% CI, 0.43 to 0.78; P = .001). Median PFS among those with exon 19 deletions and L858R EGFR mutations (n = 308) was 13.6 months for afatinib and 6.9 months for chemotherapy (HR, 0.47; 95% CI, 0.34 to 0.65; P = .001). The most common treatment-related adverse events were diarrhea, rash/acne, and stomatitis for afatinib and nausea, fatigue, and decreased appetite for chemotherapy. PROs favored afatinib, with better control of cough, dyspnea, and pain. Afatinib is associated with prolongation of PFS when compared with standard doublet chemotherapy in patients with advanced lung adenocarcinoma and EGFR mutations.
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        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.

         J Shi,  Yang Shi,  Long Wu (2014)
        Afatinib-an oral irreversible ErbB family blocker-improves progression-free survival compared with pemetrexed and cisplatin for first-line treatment of patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). We compared afatinib with gemcitabine and cisplatin-a chemotherapy regimen widely used in Asia-for first-line treatment of Asian patients with EGFR mutation-positive advanced NSCLC. This open-label, randomised phase 3 trial was done at 36 centres in China, Thailand, and South Korea. After central testing for EGFR mutations, treatment-naive patients (stage IIIB or IV cancer [American Joint Committee on Cancer version 6], performance status 0-1) were randomly assigned (2:1) to receive either oral afatinib (40 mg per day) or intravenous gemcitabine 1000 mg/m(2) on day 1 and day 8 plus cisplatin 75 mg/m(2) on day 1 of a 3-week schedule for up to six cycles. Randomisation was done centrally with a random number-generating system and an interactive internet and voice-response system. Randomisation was stratified by EGFR mutation (Leu858Arg, exon 19 deletions, or other; block size three). Clinicians and patients were not masked to treatment assignment, but the independent central imaging review group were. Treatment continued until disease progression, intolerable toxic effects, or withdrawal of consent. The primary endpoint was progression-free survival assessed by independent central review (intention-to-treat population). This study is registered with, NCT01121393. 910 patients were screened and 364 were randomly assigned (242 to afatinib, 122 to gemcitabine and cisplatin). Median progression-free survival was significantly longer in the afatinib group (11·0 months, 95% CI 9·7-13·7) than in the gemcitabine and cisplatin group (5·6 months, 5·1-6·7; hazard ratio 0·28, 95% CI 0·20-0·39; p<0·0001). The most common treatment-related grade 3 or 4 adverse events in the afatinib group were rash or acne (35 [14·6%] of 239 patients), diarrhoea (13 [5·4%]), and stomatitis or mucositis (13 [5·4%]), compared with neutropenia (30 [26·5%] of 113 patients), vomiting (22 [19·5%]), and leucopenia (17 [15·0%]) in the gemcitabine and cisplatin group. Treatment-related serious adverse events occurred in 15 (6·3%) patients in the afatinib group and nine (8·0%) patients in the gemcitabine and cisplatin group. First-line afatinib significantly improves progression-free survival with a tolerable and manageable safety profile in Asian patients with EGFR mutation-positive advanced lung NSCLC. Afatinib should be considered as a first-line treatment option for this patient population. Boehringer Ingelheim. Copyright © 2014 Elsevier Ltd. All rights reserved.
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          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.

          We aimed to assess the effect of afatinib on overall survival of patients with EGFR mutation-positive lung adenocarcinoma through an analysis of data from two open-label, randomised, phase 3 trials.

            Author and article information

            [1 ]GRID grid.468189.a, Department of Solid Tumor Oncology and Investigational Therapeutics, , Levine Cancer Institute, Carolinas HealthCare System, ; Charlotte, NC USA
            [2 ]ISNI 0000000419368729, GRID grid.21729.3f, Division of Hematology/Oncology, , Columbia University, ; New York, NY USA
            [3 ]ISNI 0000 0004 1936 8972, GRID grid.25879.31, Division of Hematology/Oncology, Department of Medicine, Abramson Cancer Center, , University of Pennsylvania, ; Philadelphia, PA USA
            [4 ]Medical Oncology/Hematology, Zangmeister Center, Columbus, OH USA
            [5 ]ISNI 0000 0004 0447 7316, GRID grid.416912.9, University of Florida Health Cancer Center, , Orlando Health, ; Orlando, FL USA
            [6 ]Virginia Cancer Specialists Research Institute, Fairfax, VA USA
            [7 ]Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria
            [8 ]ISNI 0000 0001 1312 9717, GRID grid.418412.a, , Boehringer Ingelheim Pharmaceuticals, Inc., ; Ridgefield, CT USA
            [9 ]ISNI 0000 0001 2171 7500, GRID grid.420061.1, , Boehringer Ingelheim Pharma GmbH & Co KG, ; Ingelheim am Rhein, Germany
            Oncol Ther
            Oncol Ther
            Oncology and Therapy
            Springer Healthcare (Cheshire )
            10 April 2017
            10 April 2017
            : 5
            : 1
            : 103-110
            5488108 43 10.1007/s40487-017-0043-5
            © The Author(s) 2017
            Funded by: FundRef, Boehringer Ingelheim ;
            Brief Report
            Custom metadata
            © Springer Healthcare Ltd. 2017


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