A randomized, double-blind, phase III, non-inferiority clinical trial comparing the efficacy and safety of TA4415V (a proposed Trastuzumab biosimilar) and Herceptin (Trastuzumab reference product) in HER2-positive early-stage breast Cancer patients
Abstract Background This study compared efficacy and safety of TA4415V, a trastuzumab biosimilar, with reference trastuzumab in patients with human epidermal growth factor receptor 2–positive (HER2-positive) early-stage breast cancer treated in the neoadjuvant setting in Iran. Methods Patients were...
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | BMC Pharmacology and Toxicology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40360-022-00599-x |
| _version_ | 1818501843898073088 |
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| author | Reza Safaei Nodehi Behjat Kalantari Jahangir Raafat Nafiseh Ansarinejad Vahid Moazed Seyed Mohammad Reza Mortazavizadeh Mehran Hosseinzadeh Bayazid Ghaderi Arash Jenabian Mojtaba Qadyani Shirin Haghighat Abolghasem Allahyari Mehrzad Mirzania Mohammad Seghatoleslami Mehrdad Payandeh Afsaneh Alikhasi Hamidreza Kafi Farhad Shahi |
| author_facet | Reza Safaei Nodehi Behjat Kalantari Jahangir Raafat Nafiseh Ansarinejad Vahid Moazed Seyed Mohammad Reza Mortazavizadeh Mehran Hosseinzadeh Bayazid Ghaderi Arash Jenabian Mojtaba Qadyani Shirin Haghighat Abolghasem Allahyari Mehrzad Mirzania Mohammad Seghatoleslami Mehrdad Payandeh Afsaneh Alikhasi Hamidreza Kafi Farhad Shahi |
| author_sort | Reza Safaei Nodehi |
| collection | DOAJ |
| description | Abstract Background This study compared efficacy and safety of TA4415V, a trastuzumab biosimilar, with reference trastuzumab in patients with human epidermal growth factor receptor 2–positive (HER2-positive) early-stage breast cancer treated in the neoadjuvant setting in Iran. Methods Patients were randomly assigned to receive neoadjuvant TA4415V or reference trastuzumab concurrently with docetaxel (TH phase) for 4 cycles after treatment with 4 cycles of doxorubicin and cyclophosphamide (AC phase). Chemotherapy was followed by surgery. The primary endpoint was the comparison of pathologic complete response (pCR) rate in the per-protocol population. Secondary endpoints included comparisons of overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity. Results Ninety-two participants were analyzed in the per-protocol population (TA4415V, n = 48; reference trastuzumab, n = 44). The pCR rates were 37.50% and 34.09% with TA4415V and reference drug, respectively. The 95% CI of the estimated treatment outcome difference (− 0·03 [95% CI − 0.23 to 0.16]) was within the non-inferiority margin. No statistically significant difference was observed between the groups for other efficacy variables in the ITT population: ORR (89.13% vs. 83.33%; p = 0.72) and BCS (20.37% vs. 12.96%; p = 0.42) in the TA4415V and reference drug group, respectively. At least one grade 3 or 4 adverse events occurred in 27 (50%) patients in the TA4415V group versus 29 (53.70%) in the reference trastuzumab group (p = 0.70). The decrease in left ventricular ejection fraction (LVEF), as an adverse event of special interest (AESI) for trastuzumab, was compared between treatment groups in TH phase. Results demonstrated an LVEF decrease in 7 (12.96%) and 9 (16.67%) patients in TA4415V and reference trastuzumab groups, respectively (p = 0.59). Anti-drug antibodies (ADA) were not detected in any samples of groups. Conclusions Non-inferiority for efficacy was demonstrated between TA4415V and Herceptin based on the ratio of pCR rates in HER2-positive early breast cancer patients. In addition, ORR and BCS, as secondary endpoints, were not significantly different. Safety profile and immunogenicity were also comparable between the two groups. |
| first_indexed | 2024-12-10T21:01:53Z |
| format | Article |
| id | doaj.art-90c12cf33ccd4cea98f2bc6387e4d2da |
| institution | Directory Open Access Journal |
| issn | 2050-6511 |
| language | English |
| last_indexed | 2024-12-10T21:01:53Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pharmacology and Toxicology |
| spelling | doaj.art-90c12cf33ccd4cea98f2bc6387e4d2da2022-12-22T01:33:47ZengBMCBMC Pharmacology and Toxicology2050-65112022-07-0123111010.1186/s40360-022-00599-xA randomized, double-blind, phase III, non-inferiority clinical trial comparing the efficacy and safety of TA4415V (a proposed Trastuzumab biosimilar) and Herceptin (Trastuzumab reference product) in HER2-positive early-stage breast Cancer patientsReza Safaei Nodehi0Behjat Kalantari1Jahangir Raafat2Nafiseh Ansarinejad3Vahid Moazed4Seyed Mohammad Reza Mortazavizadeh5Mehran Hosseinzadeh6Bayazid Ghaderi7Arash Jenabian8Mojtaba Qadyani9Shirin Haghighat10Abolghasem Allahyari11Mehrzad Mirzania12Mohammad Seghatoleslami13Mehrdad Payandeh14Afsaneh Alikhasi15Hamidreza Kafi16Farhad Shahi17Department of Internal Medicine, Hematology and Medical Oncology Ward, Cancer Research Center, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical SciencesDepartment of Internal Medicine, School of Medicine, Kerman University of Medical SciencesCancer Research Institute, School of Medicine, Tehran University of Medical SciencesIran University of Medical SciencesDepartment of Internal Medicine, School of Medicine, Kerman University of Medical SciencesDepartment of Internal, Faculty of Medicine, Islamic Azad UniversityJundishapour University of Medical SciencesLiver and Digestive Research Center, Kurdistan University of Medical SciencesDepartment of Medical Oncology and Hematology, Boali Hospital, Tehran Medical Sciences, Islamic Azad UniversityTaleghani Hospital, Shaheed Beheshti University of Medical SciencesHematology Research Center, Department of Hematology, Medical Oncology, and Stem Cell Transplantation, Shiraz University of Medical SciencesDivision of Hematology and Medical Oncology, Emam Reza Hospital, Mashhad University of Medical SciencesHematology and Medical Oncology Department, Cancer Institute, Tehran University of Medical SciencesHealth Research Institute, Research Center of Thalassemia & Hemoglobinopathy, Ahvaz Jundishapur University of Medical SciencesRegenerative Medicine Research Center, Kermanshah University of Medical SciencesDepartment of Radiology, Cancer Institute of Iran, Tehran University of Medical SciencesMedical Department, Orchid Pharmed CompanyDepartment of Internal Medicine, Hematology and Medical Oncology Ward, Cancer Research Center, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical SciencesAbstract Background This study compared efficacy and safety of TA4415V, a trastuzumab biosimilar, with reference trastuzumab in patients with human epidermal growth factor receptor 2–positive (HER2-positive) early-stage breast cancer treated in the neoadjuvant setting in Iran. Methods Patients were randomly assigned to receive neoadjuvant TA4415V or reference trastuzumab concurrently with docetaxel (TH phase) for 4 cycles after treatment with 4 cycles of doxorubicin and cyclophosphamide (AC phase). Chemotherapy was followed by surgery. The primary endpoint was the comparison of pathologic complete response (pCR) rate in the per-protocol population. Secondary endpoints included comparisons of overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity. Results Ninety-two participants were analyzed in the per-protocol population (TA4415V, n = 48; reference trastuzumab, n = 44). The pCR rates were 37.50% and 34.09% with TA4415V and reference drug, respectively. The 95% CI of the estimated treatment outcome difference (− 0·03 [95% CI − 0.23 to 0.16]) was within the non-inferiority margin. No statistically significant difference was observed between the groups for other efficacy variables in the ITT population: ORR (89.13% vs. 83.33%; p = 0.72) and BCS (20.37% vs. 12.96%; p = 0.42) in the TA4415V and reference drug group, respectively. At least one grade 3 or 4 adverse events occurred in 27 (50%) patients in the TA4415V group versus 29 (53.70%) in the reference trastuzumab group (p = 0.70). The decrease in left ventricular ejection fraction (LVEF), as an adverse event of special interest (AESI) for trastuzumab, was compared between treatment groups in TH phase. Results demonstrated an LVEF decrease in 7 (12.96%) and 9 (16.67%) patients in TA4415V and reference trastuzumab groups, respectively (p = 0.59). Anti-drug antibodies (ADA) were not detected in any samples of groups. Conclusions Non-inferiority for efficacy was demonstrated between TA4415V and Herceptin based on the ratio of pCR rates in HER2-positive early breast cancer patients. In addition, ORR and BCS, as secondary endpoints, were not significantly different. Safety profile and immunogenicity were also comparable between the two groups.https://doi.org/10.1186/s40360-022-00599-xBreast CancerTrastuzumab, biosimilarNon-inferiorityRandomized clinical trial |
| spellingShingle | Reza Safaei Nodehi Behjat Kalantari Jahangir Raafat Nafiseh Ansarinejad Vahid Moazed Seyed Mohammad Reza Mortazavizadeh Mehran Hosseinzadeh Bayazid Ghaderi Arash Jenabian Mojtaba Qadyani Shirin Haghighat Abolghasem Allahyari Mehrzad Mirzania Mohammad Seghatoleslami Mehrdad Payandeh Afsaneh Alikhasi Hamidreza Kafi Farhad Shahi A randomized, double-blind, phase III, non-inferiority clinical trial comparing the efficacy and safety of TA4415V (a proposed Trastuzumab biosimilar) and Herceptin (Trastuzumab reference product) in HER2-positive early-stage breast Cancer patients BMC Pharmacology and Toxicology Breast Cancer Trastuzumab, biosimilar Non-inferiority Randomized clinical trial |
| title | A randomized, double-blind, phase III, non-inferiority clinical trial comparing the efficacy and safety of TA4415V (a proposed Trastuzumab biosimilar) and Herceptin (Trastuzumab reference product) in HER2-positive early-stage breast Cancer patients |
| title_full | A randomized, double-blind, phase III, non-inferiority clinical trial comparing the efficacy and safety of TA4415V (a proposed Trastuzumab biosimilar) and Herceptin (Trastuzumab reference product) in HER2-positive early-stage breast Cancer patients |
| title_fullStr | A randomized, double-blind, phase III, non-inferiority clinical trial comparing the efficacy and safety of TA4415V (a proposed Trastuzumab biosimilar) and Herceptin (Trastuzumab reference product) in HER2-positive early-stage breast Cancer patients |
| title_full_unstemmed | A randomized, double-blind, phase III, non-inferiority clinical trial comparing the efficacy and safety of TA4415V (a proposed Trastuzumab biosimilar) and Herceptin (Trastuzumab reference product) in HER2-positive early-stage breast Cancer patients |
| title_short | A randomized, double-blind, phase III, non-inferiority clinical trial comparing the efficacy and safety of TA4415V (a proposed Trastuzumab biosimilar) and Herceptin (Trastuzumab reference product) in HER2-positive early-stage breast Cancer patients |
| title_sort | randomized double blind phase iii non inferiority clinical trial comparing the efficacy and safety of ta4415v a proposed trastuzumab biosimilar and herceptin trastuzumab reference product in her2 positive early stage breast cancer patients |
| topic | Breast Cancer Trastuzumab, biosimilar Non-inferiority Randomized clinical trial |
| url | https://doi.org/10.1186/s40360-022-00599-x |
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