Filippo de Marinis1, Konstantin K Laktionov2, Artem Poltoratskiy3, Inna Egorova4, Maximilian Hochmair5, Antonio Passaro6, Maria Rita Migliorino7, Giulio Metro8, Maya Gottfried9, Daphne Tsoi10, Gyula Ostoros11, Simona Rizzato12, Guzel Z Mukhametshina13, Michael Schumacher14, Silvia Novello15, Rafal Dziadziuszko16, Wenbo Tang17, Laura Clementi18, Agnieszka Cseh19, Dariusz Kowalski20. 1. European Institute of Oncology IRCCS, Milan, Italy. Electronic address: Filippo.DeMarinis@ieo.it. 2. Federal State Budgetary Institution "N.N.Blokhin National Medical Research Center of Oncology" of the Ministry of Health of the Russian Federation (N.N. Blokhin NMRCO), Moscow, Russia. 3. Petrov Research Institute of Oncology, St Petersburg, Russia. 4. Clinical Oncology Dispensary, St Petersburg, Russia. 5. Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Vienna, Austria. 6. European Institute of Oncology IRCCS, Milan, Italy. 7. San Camillo-Forlanini Hospital, Rome, Italy. 8. Santa Maria della Misericordia Hospital, Perugia, Italy. 9. Tel Aviv University, Tel Aviv, Israel. 10. St John of God Murdoch Hospital, Murdoch, WA, Australia. 11. National Korányi Institute for Pulmonology, Budapest, Hungary. 12. Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy. 13. Ministry of Health of the Republic of Tatarstan, Kazan, Russia. 14. Ordensklinikum Elisabethinen, Linz, Austria. 15. University of Turin, AOU San Luigi, Orbassano, Italy. 16. Medical University of Gdansk, Gdansk, Poland. 17. Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA. 18. Boehringer Ingelheim Italia S.p.A., Milan, Italy. 19. Boehringer Ingelheim International, Ingelheim, Germany. 20. Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Abstract
OBJECTIVES: Randomized controlled trials have demonstrated that afatinib is a suitable treatment option for patients with epidermal growth factor receptor mutation-positive (EGFRm +) non-small cell lung cancer (NSCLC). However, such studies often exclude patients treated in routine clinical practice. We report interim results from a Phase 3b, open-label, multicenter, single-arm, exploratory trial, in which afatinib was investigated in a real-world setting. MATERIALS AND METHODS: Patients with EGFRm + tyrosine kinase inhibitor (TKI)-naïve NSCLC received afatinib 40 mg orally, once-daily, until disease progression, or voluntary withdrawal. Primary objective was safety. RESULTS: Overall, 479 patients received afatinib: median age 65 years, 8 % of patients had an ECOG performance status ≥ 2, 17 % had brain metastases, and 13 % had tumors containing uncommon mutations only. All but one patient (99.8 %) had an adverse event (AE). Treatment-related AEs (TRAEs; any/grade ≥ 3) occurred in 97 %/44 % of patients; most common were diarrhea (87 %/16 %) and rash (51 %/11 %). AEs leading to afatinib dose-reduction were reported in 258 patients (54 %), and 37 patients (8 %) discontinued treatment due to a TRAE. Objective response rate was 45.5 %, median duration of response was 14.1 months (95 % CI: 12.2-16.4). Overall median time to symptomatic progression and progression-free survival were 14.9 months (95 % CI: 13.8-17.6) and 13.4 months (95 % CI: 11.8-14.5), respectively, in the overall population and 19.3 months (95 % CI: 15.6-21.8) and 15.9 months (95 % CI: 13.9-19.1) in patients with EGFR exon 19 deletions. CONCLUSIONS: Afatinib administration in routine clinical practice was well tolerated with no new safety signals and demonstrated promising efficacy in patients with EGFRm + NSCLC. TRAEs were generally manageable with tolerability-guided dose reductions. Overall, these data independently support findings from randomized controlled trials of afatinib in EGFRm + NSCLC.
OBJECTIVES: Randomized controlled trials have demonstrated that afatinib is a suitable treatment option for patients with epidermal growth factor receptor mutation-positive (EGFRm +) non-small cell lung cancer (NSCLC). However, such studies often exclude patients treated in routine clinical practice. We report interim results from a Phase 3b, open-label, multicenter, single-arm, exploratory trial, in which afatinib was investigated in a real-world setting. MATERIALS AND METHODS:Patients with EGFRm + tyrosine kinase inhibitor (TKI)-naïve NSCLC received afatinib 40 mg orally, once-daily, until disease progression, or voluntary withdrawal. Primary objective was safety. RESULTS: Overall, 479 patients received afatinib: median age 65 years, 8 % of patients had an ECOG performance status ≥ 2, 17 % had brain metastases, and 13 % had tumors containing uncommon mutations only. All but one patient (99.8 %) had an adverse event (AE). Treatment-related AEs (TRAEs; any/grade ≥ 3) occurred in 97 %/44 % of patients; most common were diarrhea (87 %/16 %) and rash (51 %/11 %). AEs leading to afatinib dose-reduction were reported in 258 patients (54 %), and 37 patients (8 %) discontinued treatment due to a TRAE. Objective response rate was 45.5 %, median duration of response was 14.1 months (95 % CI: 12.2-16.4). Overall median time to symptomatic progression and progression-free survival were 14.9 months (95 % CI: 13.8-17.6) and 13.4 months (95 % CI: 11.8-14.5), respectively, in the overall population and 19.3 months (95 % CI: 15.6-21.8) and 15.9 months (95 % CI: 13.9-19.1) in patients with EGFR exon 19 deletions. CONCLUSIONS:Afatinib administration in routine clinical practice was well tolerated with no new safety signals and demonstrated promising efficacy in patients with EGFRm + NSCLC. TRAEs were generally manageable with tolerability-guided dose reductions. Overall, these data independently support findings from randomized controlled trials of afatinib in EGFRm + NSCLC.
Authors: Mingjun Rui; Zijing Wang; Zhengyang Fei; Yao Wu; Yingcheng Wang; Lei Sun; Ye Shang; Hongchao Li Journal: Front Pharmacol Date: 2022-03-16 Impact factor: 5.810
Authors: Antonio Passaro; Filippo de Marinis; Hai-Yan Tu; Konstantin K Laktionov; Jifeng Feng; Artem Poltoratskiy; Jun Zhao; Eng Huat Tan; Maya Gottfried; Victor Lee; Dariusz Kowalski; Cheng Ta Yang; B J Srinivasa; Laura Clementi; Tejaswini Jalikop; Dennis Chin Lun Huang; Agnieszka Cseh; Keunchil Park; Yi-Long Wu Journal: Front Oncol Date: 2021-07-09 Impact factor: 6.244