Phase II study of afatinib, an irreversible ErbB family blocker, in demographically and genotypically defined lung adenocarcinoma. Issue 1 (April 2015)

• Record Type: Journal Article
• Authors: De Grève, Jacques; Moran, Teresa; Graas, Marie-Pascale; Galdermans, Daniella; Vuylsteke, Peter; Canon, Jean-Luc; Schallier, Denis; Decoster, Lore; Teugels, Erik; Massey, Dan; Chand, Vikram K.; Vansteenkiste, Johan
• Is Part Of: Lung cancer. Volume 88:Issue 1(2015:Apr.)
• Page Start: 63
• Page End: 69
• Publication Date: 2015-04
• Subjects: AEs adverse events -- Cpre, ss pre-dose plasma concentrations at steady state -- CR complete response -- DCRs disease control rates -- EGFR epidermal growth factor receptor -- FISH fluorescence in situ hybridization -- FISH+ fluorescence in situ hybridization positive -- gMean geometric mean -- HER2 human epidermal growth factor receptor-2 -- M+ mutation positive -- NSCLC non-small cell lung cancer -- OR objective response -- PCR polymerase chain reaction -- PD progressive disease -- PFS progression-free survival -- PR partial response -- PS performance status -- RECIST Response Evaluation Criteria in Solid Tumors -- SD stable disease -- TKIs tyrosine kinase inhibitors -- WT wild-type; Afatinib -- EGFR -- HER2 -- ErbB -- Paclitaxel -- Non-small cell lung cancer; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2015.01.013
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Afatinib monotherapy was active in NSCLC tumors with HER2 activating mutations. Afatinib monotherapy was active in NSCLC tumors overexpressing wild-type EGFR. Afatinib + paclitaxel was active in NSCLC patients after progression on afatinib. Afatinib displayed a predictable and manageable safety profile. Abstract: Objectives: Afatinib, an oral irreversible ErbB family blocker, has demonstrated efficacy in patients with epidermal growth factor receptor ( EGFR ) mutation-positive advanced lung adenocarcinoma. Other potential biomarkers predicting response to afatinib, such as human epidermal growth factor receptor-2 ( HER2 ) mutations and EGFR gene amplification, have not been validated yet. This phase II study investigated whether afatinib conferred clinical benefit in cohorts of adenocarcinoma patients with: (1) EGFR mutation and failing on erlotinib/gefitinib; or (2) increased copy number of EGFR by fluorescence in situ hybridization (FISH); or (3) HER2 mutation. Materials and methods: Patients started daily afatinib 50 mg monotherapy. Upon disease progression, patients could continue, at the investigator's discretion, afatinib (40 mg) with the addition of paclitaxel (80 mg/m 2 weekly for 3 weeks/4-week cycle). Endpoints included confirmed objective response (OR), progression-free survival (PFS), disease control, and safety. Results: Of 41 patients treated (cohort 1: n = 32; cohort 2: n = 2; cohort 3: n = 7), 33 received afatinib monotherapy; eight subsequently received afatinib plus paclitaxel. With afatinib monotherapy, one patient achieved a confirmed OR (partial response [PR]; cohort 2). Two further patients achieved unconfirmed PRs (one each in cohort 1 and cohort 3). Disease control was achieved by 17/32 (53%), 2/2 (100%) and 5/7 (71%) patients in cohorts 1, 2 and 3, respectively. In patients receiving combination therapy (median PFS: 6.7 weeks), one (cohort 3) had confirmed PR of 41.9 weeks. The most common afatinib-related adverse events were diarrhea (95%) and rash/acne (80%). Conclusion: Afatinib demonstrated signs of clinical activity in heavily pretreated patients with activating HER2 or EGFR mutations or EGFR FISH-positive tumors.