Jacques De Grève1, Teresa Moran2, Marie-Pascale Graas3, Daniella Galdermans4, Peter Vuylsteke5, Jean-Luc Canon6, Denis Schallier7, Lore Decoster8, Erik Teugels9, Dan Massey10, Vikram K Chand11, Johan Vansteenkiste12. 1. Medical Oncology, Oncologisch Centrum, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. Electronic address: jacques.degreve@uzbrussel.be. 2. Institut Catala d'Oncologia, Hospital Germans Trias I Pujol, Universitat Autònoma de Barcelona, Departament de Medicina, Badalona, Spain. Electronic address: mmoran@iconcologia.net. 3. Centre Hospitalier Chrétien, Liège, Belgium. Electronic address: marie-pascale.graas@chc.be. 4. ZNA Middelheim Hospital, Antwerp, Belgium. Electronic address: danny.galdermans@pandora.be. 5. Clinique et Maternité Sainte-Elisabeth, Medical Oncology, Namur, Belgium. Electronic address: peter.vuylsteke@cmsenamur.be. 6. Grand Hospital de Charleroi, Oncologie-Hématologie, Grand Rue 3, Charleroi 6000, Belgium. Electronic address: jean_luc.canon@ghdc.be. 7. Medical Oncology, Oncologisch Centrum, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. Electronic address: denis.schallier@uzbrussel.be. 8. Medical Oncology, Oncologisch Centrum, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. Electronic address: lore.decoster@uzbrussel.be. 9. Medical Oncology, Oncologisch Centrum, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. Electronic address: Erik.Teugels@uzbrussel.be. 10. Boehringer Ingelheim, Ltd., Bracknell, Berkshire, UK. Electronic address: dan.massey.ext@boehringer-ingelheim.com. 11. Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA. Electronic address: vikram.chand@boehringer-ingelheim.com. 12. Respiratory Oncology Unit, Department of Pulmonology, University Hospitals KU Leuven, Leuven, Belgium. Electronic address: johan.vansteenkiste@uz.kuleuven.ac.be.
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 50mg monotherapy. Upon disease progression, patients could continue, at the investigator's discretion, afatinib (40mg) with the addition of paclitaxel (80mg/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.
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 humanepidermal 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 adenocarcinomapatients 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 50mg monotherapy. Upon disease progression, patients could continue, at the investigator's discretion, afatinib (40mg) with the addition of paclitaxel (80mg/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 EGFRFISH-positive tumors.
Authors: Alessandro Russo; Ana Rita Lopes; Michael G McCusker; Sandra Gimenez Garrigues; Giuseppina R Ricciardi; Katherine E Arensmeyer; Katherine A Scilla; Ranee Mehra; Christian Rolfo Journal: Curr Oncol Rep Date: 2020-04-16 Impact factor: 5.075
Authors: Bob T Li; Adrian Lee; Sandra O'Toole; Wendy Cooper; Bing Yu; Jamie E Chaft; Maria E Arcila; Mark G Kris; Nick Pavlakis Journal: Lung Cancer Date: 2015-10-29 Impact factor: 5.705
Authors: Elena Ivanova; Mari Kuraguchi; Man Xu; Andrew J Portell; Luke Taus; Irmina Diala; Alshad S Lalani; Jihyun Choi; Emily S Chambers; Shuai Li; Shengwu Liu; Ting Chen; Thanh U Barbie; Geoffrey R Oxnard; Jacob J Haworth; Kwok-Kin Wong; Suzanne E Dahlberg; Amir A Aref; David A Barbie; Magda Bahcall; Cloud P Paweletz; Pasi A Jänne Journal: Clin Cancer Res Date: 2020-02-07 Impact factor: 12.531