Produção Nacional
Revisado por pares
Efficacy, Safety and Immunogenicity of MB02 (Bevacizumab Biosimilar) versus Reference Bevacizumab in Advanced Non-Small Cell Lung Cancer: A Randomized, Double-Blind, Phase III Study (STELLA)
2021; Adis, Springer Healthcare; Volume: 35; Issue: 4 Linguagem: Inglês
10.1007/s40259-021-00483-w
ISSN1179-190X
AutoresDmytro Trukhin, Elena Poddubskaya, Zoran Andrić, Tamta Makharadze, Ravi Shankar Bellala, Chaiyut Charoentum, Eduardo Patricio Yanez Ruiz, Andrea Fülöp, Irfhan Ali Hyder Ali, Kostas Syrigos, Nuran Katgı, Yamil Alonso Lopez Chuken, Ilieva Rumyana, Jasmin Reyes-Igama, Rita de Cassia Costamilan, Ana Del Campo García, Amalia Florez, Alexandra Paravisini, Susana Millán, Luiz H. Araujo, Carla Maria de Oliveira Ferreira, Hélio Pinczowski, Maria Marcela Fernandes Monteiro, Assen Dudov, Janeta Syrova, Francisco Javier Orlandi Jorquera, Carlos Eduardo Gallardo Arenada, Christian Lorenzo Caglevic Medina, Davit Giorgadze, Nino Mchedlidze, Vladimer Kuchava, Tamar Melkadze, Amiran Matitashvili, Nana Chikhladze, E Samantas, Theodoros Kontakiotis, Beatrix Bálint, Balazs Medgyasszay, Eszter Csánky, Shailesh Bondarde, Lovenish Goyal, Ajay Sharma, Baijumon Balan, Prabrajya Narayan Mohapatra, Kaushalkumar Babubhai Patel, Sachin Sharadchandra Hingmire, Mithun Satish Shah, Kartikeya Jain, Ashish Agrawal, Prashant Kumbhaj, Asis Mukhopadhyay, Paul Khoueiry, Suhana Yusak, Yong Kek Pang, V. Pei Jye, Prathepamalar Yehgambaram, Fuad Ismail, Gokula Kumar Appalanaido, Feliciano Barrón, Ma. Noemi Uy, Felycette Gay Martinez-Lapus, Maria Belen Tamayo, Jennifer Sandoval-Tan, Jamela Anne Osorio Sanchez, Christina G. Galvez, Josephine Contreras-Tolentino, Evgeny Ledin, Daniil Stroyakovskiy, I. V. Kudryavtsev, Vladimir Vladimirov, Evgeniy Gotovkin, М. В. Шомова, Guzel Mukhametshina, Igor Lifirenko, Nina Karaseva, M. Nechaeva, Anna V. Tarasova, Alexander Luft, Lyudmila Kuzina, Marina Petrović, Milan Rančić, Borjan Zaric, Manoch Buranachokphaisan, Sarayut Lucien Geater, Ekkapong Tharavichitkul, Mahmut Gümüş, Igor Bondarenko, Yaroslav Shparyk, Serhii Shevnia, Iryna Lytvyn, Oleksii Kolesnik, Yevhen Hotko, Ivan Sinielnikov, Hryhoriy Adamchuk, Grygorii Ursol, О. І. Іващук, Yuriy Ostapenko, Tetiana Popovska,
Tópico(s)Biosimilars and Bioanalytical Methods
ResumoMB02 (bevacizumab biosimilar) showed similar structural, functional, and pharmacokinetic properties to reference bevacizumab (Avastin®; EU-bevacizumab). To confirm clinical similarity between MB02 and EU-bevacizumab, a comparability study was undertaken in the first-line treatment of stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC). This multinational, double-blind, randomized, phase III study (STELLA) compared MB02 or EU-bevacizumab (15 mg/kg) administered with chemotherapy (paclitaxel 200 mg/m2 and carboplatin AUC6) on Day 1 of every 3-week cycle for 6 cycles (Week 18), followed by MB02/EU-bevacizumab in blinded monotherapy until disease progression, unacceptable toxicity, death, withdrawal of consent or end of study (Week 52). The primary efficacy endpoint was objective response rate (ORR) evaluated by an independent radiological review committee (IRC) at Week 18 (intent-to-treat population). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety and immunogenicity. A total of 627 subjects were randomized 1:1 to MB02 (n = 315) or EU-bevacizumab (n = 312). ORR, assessed by the IRC at Week 18, was comparable in MB02 (40.3%) and EU-bevacizumab (44.6%) groups. ORR risk ratio of 0.910 (90% CI 0.780 to 1.060; 95% CI 0.758 to 1.092) and ORR risk difference of −4.02 (90% CI −10.51 to 2.47; 95% CI −11.76 to 3.71) were within the similarity predefined margins. There were no significant differences between MB02 and EU-bevacizumab groups in median PFS (36.0 vs 37.3 weeks, respectively; HR 1.187; 95% CI 0.98 to 1.44) and median OS (not achieved; HR 1.108; 95% CI: 0.83 to 1.49) at the end of study. The safety profile of MB02 and EU-bevacizumab regarding nature, frequency and severity of the adverse events (AE) was comparable. The most frequent grade ≥3 investigational-product-related AEs were hypertension and anemia, with a difference between treatment groups of <5%. Anti-drug antibodies (ADA) and neutralizing ADA (NAb) incidence were similar in both treatment groups. MB02 demonstrated similar efficacy to EU-bevacizumab, in combination with carboplatin and paclitaxel, in subjects with advanced non-squamous NSCLC, with comparable safety and immunogenicity profiles. EudraCT No. 2017-001769-26; ClinicalTrials.gov: NCT03296163.
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