Claire Verschraegen1, Zoran Andric2, Fedor Moiseenko3, Tamta Makharadze4, Sergii Shevnya5, Alona Oleksiienko6, Eduardo Yañez Ruiz7, SungHyun Kim8, KeumYoung Ahn8, TaeHong Park8, Sijin Park8, Hana Ju8, Yuichiro Ohe9. 1. The Ohio State University Comprehensive Cancer Center, 1800 Cannon Road - Lincoln Tower 1300, Columbus, OH, 43210, USA. 2. Clinical Hospital Center Bezanijska Kosa, Dr Zorza Matea bb, Belgrade, 11000, Serbia. 3. GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology) - Hospital, Ulitsa Leningradskaya 68a Litera A, Poselok Pesochny, St Petersburg, Leningradskaya Oblast, 197758, Russian Federation. 4. LTD "High Technology Hospital Medcenter", 118 Pushkini Street, Batumi, 6000, Georgia. 5. Communal Nonprofit Enterprise Podilsky Regional Center of Oncology of the Vinnytsia Regional Council, 84 Khmelnytske Road, Vinnytsia, 21029, Ukraine. 6. Treatment and Diagnostic Center of LLC Specialized Clinic Prognosis Optima, 40a Vatslava Havela Boulevard, Kyiv, 03126, Ukraine. 7. Department of Internal Medicine Oncology Unit - Hematology, School of Medicine, Universidad de la Frontera, Hochstetter 298, Temuco, 4800827, Chile. 8. Celltrion, Inc., 23 Academy-ro, Yeonsu-gu, Incheon, 22014, Republic of Korea. 9. National Cancer Center Hospital, 5-1-1 Tsukiji Chuo-ku, Tokyo, 104-0045, Japan. yohe@ncc.go.jp.
Abstract
BACKGROUND: CT-P16 is a candidate bevacizumab biosimilar. OBJECTIVE: This double-blind, multicenter, parallel-group, phase III study aimed to establish equivalent efficacy between CT-P16 and European Union-approved reference bevacizumab (EU-bevacizumab) in patients with metastatic or recurrent non-squamous non-small cell lung cancer (nsNSCLC). PATIENTS AND METHODS: Patients with stage IV or recurrent nsNSCLC were randomized (1:1) to receive CT-P16 or EU-bevacizumab (15 mg/kg every 3 weeks; ≤ 6 cycles) with paclitaxel (200 mg/m2) and carboplatin (area under the curve 6.0; both for 4-6 cycles), as induction therapy. Patients with controlled disease after induction therapy continued with CT-P16 or EU-bevacizumab maintenance therapy. The primary endpoint was objective response rate (ORR) during the induction period. Time-to-event analyses, pharmacokinetics, safety, and immunogenicity were also evaluated. Results obtained after 1 year of follow-up are presented. RESULTS: Overall, 689 patients were randomized (CT-P16, N = 342; EU-bevacizumab, N = 347). ORR was 42.40% (95% confidence interval [CI] 37.16-47.64) and 42.07% (95% CI 36.88-47.27) for CT-P16 and EU-bevacizumab, respectively. The risk difference (0.40 [95% CI - 7.02 to 7.83]) and risk ratio (1.0136 [90% CI 0.8767-1.1719]) for ORR fell within predefined equivalence margins (- 12.5 to + 12.5%, and 0.7368 to 1.3572, respectively), demonstrating equivalence between CT-P16 and EU-bevacizumab. Median response duration, time to progression, progression-free survival, and overall survival were comparable between treatment groups. Safety profiles were similar: 96.2% (CT-P16) and 93.0% (EU-bevacizumab) of patients experienced treatment-emergent adverse events. Pharmacokinetics and immunogenicity were comparable between groups. CONCLUSIONS: Equivalent efficacy and similar pharmacokinetics, safety, and immunogenicity support bioequivalence of CT-P16 and EU-bevacizumab in patients with nsNSCLC. TRIAL REGISTRATION NUMBER: NCT03676192.
BACKGROUND: CT-P16 is a candidate bevacizumab biosimilar. OBJECTIVE: This double-blind, multicenter, parallel-group, phase III study aimed to establish equivalent efficacy between CT-P16 and European Union-approved reference bevacizumab (EU-bevacizumab) in patients with metastatic or recurrent non-squamous non-small cell lung cancer (nsNSCLC). PATIENTS AND METHODS: Patients with stage IV or recurrent nsNSCLC were randomized (1:1) to receive CT-P16 or EU-bevacizumab (15 mg/kg every 3 weeks; ≤ 6 cycles) with paclitaxel (200 mg/m2) and carboplatin (area under the curve 6.0; both for 4-6 cycles), as induction therapy. Patients with controlled disease after induction therapy continued with CT-P16 or EU-bevacizumab maintenance therapy. The primary endpoint was objective response rate (ORR) during the induction period. Time-to-event analyses, pharmacokinetics, safety, and immunogenicity were also evaluated. Results obtained after 1 year of follow-up are presented. RESULTS: Overall, 689 patients were randomized (CT-P16, N = 342; EU-bevacizumab, N = 347). ORR was 42.40% (95% confidence interval [CI] 37.16-47.64) and 42.07% (95% CI 36.88-47.27) for CT-P16 and EU-bevacizumab, respectively. The risk difference (0.40 [95% CI - 7.02 to 7.83]) and risk ratio (1.0136 [90% CI 0.8767-1.1719]) for ORR fell within predefined equivalence margins (- 12.5 to + 12.5%, and 0.7368 to 1.3572, respectively), demonstrating equivalence between CT-P16 and EU-bevacizumab. Median response duration, time to progression, progression-free survival, and overall survival were comparable between treatment groups. Safety profiles were similar: 96.2% (CT-P16) and 93.0% (EU-bevacizumab) of patients experienced treatment-emergent adverse events. Pharmacokinetics and immunogenicity were comparable between groups. CONCLUSIONS: Equivalent efficacy and similar pharmacokinetics, safety, and immunogenicity support bioequivalence of CT-P16 and EU-bevacizumab in patients with nsNSCLC. TRIAL REGISTRATION NUMBER: NCT03676192.
Authors: Alan Sandler; Robert Gray; Michael C Perry; Julie Brahmer; Joan H Schiller; Afshin Dowlati; Rogerio Lilenbaum; David H Johnson Journal: N Engl J Med Date: 2006-12-14 Impact factor: 91.245
Authors: Martin Reck; Joachim von Pawel; Petr Zatloukal; Rodryg Ramlau; Vera Gorbounova; Vera Hirsh; Natasha Leighl; Jörg Mezger; Venice Archer; Nicola Moore; Christian Manegold Journal: J Clin Oncol Date: 2009-02-02 Impact factor: 44.544
Authors: Josep Garcia; Herbert I Hurwitz; Alan B Sandler; David Miles; Robert L Coleman; Regula Deurloo; Olivier L Chinot Journal: Cancer Treat Rev Date: 2020-03-26 Impact factor: 12.111