Improving treatment outcomes for patients with HER2‑positive breast cancer using neoadjuvant double HER2 blockade

Background. Dual anti-HER2-targeted therapy in breast cancer (BC) significantly increased the rate of pathological complete response (pCR) compared to single blockade when added to chemotherapy. However, limited data exist on the long-term impact on survival of the additional increase in pCR.Aim. To...

Full description

Saved in:
Bibliographic Details
Main Authors: V. F. Semiglazov, N. B. Bekkeldieva, P. V. Krivorotko, A. V. Komyakhov, R. M. Paltuev, A. I. Tseluyko, L. P. Gigolaeva, T. T. Tabagua, E. K. Zhiltsova, V. S. Apollonova, G. A. Dashyan, A. G. Kudaybergenova, V. G. Ivanov, A. A. Bozhok, D. G. Ulrikh, A. O. Gorina, T. Yu. Semiglazova
Format: Article
Language:Russian
Published: ABV-press 2024-11-01
Series:Опухоли женской репродуктивной системы
Subjects:
Online Access:https://ojrs.abvpress.ru/ojrs/article/view/1272
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849399200999014400
author V. F. Semiglazov
N. B. Bekkeldieva
P. V. Krivorotko
A. V. Komyakhov
R. M. Paltuev
A. I. Tseluyko
L. P. Gigolaeva
T. T. Tabagua
E. K. Zhiltsova
V. S. Apollonova
G. A. Dashyan
A. G. Kudaybergenova
V. G. Ivanov
A. A. Bozhok
D. G. Ulrikh
A. O. Gorina
T. Yu. Semiglazova
author_facet V. F. Semiglazov
N. B. Bekkeldieva
P. V. Krivorotko
A. V. Komyakhov
R. M. Paltuev
A. I. Tseluyko
L. P. Gigolaeva
T. T. Tabagua
E. K. Zhiltsova
V. S. Apollonova
G. A. Dashyan
A. G. Kudaybergenova
V. G. Ivanov
A. A. Bozhok
D. G. Ulrikh
A. O. Gorina
T. Yu. Semiglazova
author_sort V. F. Semiglazov
collection DOAJ
description Background. Dual anti-HER2-targeted therapy in breast cancer (BC) significantly increased the rate of pathological complete response (pCR) compared to single blockade when added to chemotherapy. However, limited data exist on the long-term impact on survival of the additional increase in pCR.Aim. To improve recommendations regarding HER2-targeted agents and chemotherapy in the neoadjuvant treatment of BC.Materials and methods. N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia took participation in some clinical trials of neoadjuvant treatment of HER2-positive breast cancer, including NeoSphere and NeoALTTO. In multicenter, open-label, phase 2 randomised NeoSphere trial, patients with locally advanced, inflammatory, or early-stage HER2-positive BC were randomly assigned to receive four neoadjuvant cycles of trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) plus docetaxel (75 mg/m2 from every 3 weeks, increasing to 100 mg/m2 from cycle 2 if tolerated) (group A), pertuzumab (420 mg every 3 weeks) and trastuzumab plus docetaxel (group B), pertuzumab and trastuzumab (group C), or pertuzumab and docetaxel (group D). After surgery, patients received three cycles of FEC. Рatients in group C received four cycles of docetaxel prior to FEC, and trastuzumab 6 mg/kg every 3 weeks to complete 1 years treatment. In NeoALTTO trial from 455 patients 154 patients received lapatinib, 149 – trastuzumab, 152 – combination of lapatinib and trastuzumab.Results. Between 2007, and 2009, 417 patients were randomly assigned to group A (107 patients), group B (n = 107), group C (n = 107), or group D (n = 96). At clinical cutoff, 87 patients had disease progression or died. 5-year progressionfree survival rates were 81 % (95 % confidence interval (CI) 71–87) for group A, 86 % (95 % CI 72–91) for group B, 73 % for group C, and 73 % for group D (95 % CI 0.34–1.40). Disease-free survival rates were consistent with progressionfree survival rates and were 81 % (95 % CI 72–88) for group A, 84 % (95 % CI 72–91) for group B, 80 % (95 % CI 70–86) for group C, and 75 % (95 % CI 64–83) for group D. In NeoALTTO trial patients who achieved pCR had longer progressionfree survival (85 % (95 % CI 76–91)) compared with patients who did not achieve pCR (76 % (95 % CI 71–81)).Conclusion. High levels of progression-free survival and disease-free survival at 5–10-years follow-up show large and overlapping CI, but support the primary endpoint (pCR) and suggest that neoadjuvant pertuzumab is beneficial when combined with trastuzumab and docetaxel. Additionally, they suggest that pCR could be an early indicator of long-term outcome in early-stage HER2-positive BC.
format Article
id doaj-art-dc1f0f1322804aeba58072d767e4d200
institution Kabale University
issn 1994-4098
1999-8627
language Russian
publishDate 2024-11-01
publisher ABV-press
record_format Article
series Опухоли женской репродуктивной системы
spelling doaj-art-dc1f0f1322804aeba58072d767e4d2002025-08-20T03:38:23ZrusABV-pressОпухоли женской репродуктивной системы1994-40981999-86272024-11-01203162110.17650/1994-4098-2024-20-3-16-21862Improving treatment outcomes for patients with HER2‑positive breast cancer using neoadjuvant double HER2 blockadeV. F. Semiglazov0N. B. Bekkeldieva1P. V. Krivorotko2A. V. Komyakhov3R. M. Paltuev4A. I. Tseluyko5L. P. Gigolaeva6T. T. Tabagua7E. K. Zhiltsova8V. S. Apollonova9G. A. Dashyan10A. G. Kudaybergenova11V. G. Ivanov12A. A. Bozhok13D. G. Ulrikh14A. O. Gorina15T. Yu. Semiglazova16N.N. Petrov National Medical Research Oncology Center, Ministry of Health of RussiaN.N. Petrov National Medical Research Oncology Center, Ministry of Health of RussiaN.N. Petrov National Medical Research Oncology Center, Ministry of Health of RussiaN.N. Petrov National Medical Research Oncology Center, Ministry of Health of RussiaN.N. Petrov National Medical Research Oncology Center, Ministry of Health of RussiaN.N. Petrov National Medical Research Oncology Center, Ministry of Health of RussiaN.N. Petrov National Medical Research Oncology Center, Ministry of Health of RussiaN.N. Petrov National Medical Research Oncology Center, Ministry of Health of RussiaN.N. Petrov National Medical Research Oncology Center, Ministry of Health of RussiaN.N. Petrov National Medical Research Oncology Center, Ministry of Health of RussiaN.N. Petrov National Medical Research Oncology Center, Ministry of Health of RussiaN.N. Petrov National Medical Research Oncology Center, Ministry of Health of RussiaN.N. Petrov National Medical Research Oncology Center, Ministry of Health of RussiaN.N. Petrov National Medical Research Oncology Center, Ministry of Health of RussiaN.N. Petrov National Medical Research Oncology Center, Ministry of Health of RussiaN.N. Petrov National Medical Research Oncology Center, Ministry of Health of RussiaN.N. Petrov National Medical Research Oncology Center, Ministry of Health of RussiaBackground. Dual anti-HER2-targeted therapy in breast cancer (BC) significantly increased the rate of pathological complete response (pCR) compared to single blockade when added to chemotherapy. However, limited data exist on the long-term impact on survival of the additional increase in pCR.Aim. To improve recommendations regarding HER2-targeted agents and chemotherapy in the neoadjuvant treatment of BC.Materials and methods. N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia took participation in some clinical trials of neoadjuvant treatment of HER2-positive breast cancer, including NeoSphere and NeoALTTO. In multicenter, open-label, phase 2 randomised NeoSphere trial, patients with locally advanced, inflammatory, or early-stage HER2-positive BC were randomly assigned to receive four neoadjuvant cycles of trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) plus docetaxel (75 mg/m2 from every 3 weeks, increasing to 100 mg/m2 from cycle 2 if tolerated) (group A), pertuzumab (420 mg every 3 weeks) and trastuzumab plus docetaxel (group B), pertuzumab and trastuzumab (group C), or pertuzumab and docetaxel (group D). After surgery, patients received three cycles of FEC. Рatients in group C received four cycles of docetaxel prior to FEC, and trastuzumab 6 mg/kg every 3 weeks to complete 1 years treatment. In NeoALTTO trial from 455 patients 154 patients received lapatinib, 149 – trastuzumab, 152 – combination of lapatinib and trastuzumab.Results. Between 2007, and 2009, 417 patients were randomly assigned to group A (107 patients), group B (n = 107), group C (n = 107), or group D (n = 96). At clinical cutoff, 87 patients had disease progression or died. 5-year progressionfree survival rates were 81 % (95 % confidence interval (CI) 71–87) for group A, 86 % (95 % CI 72–91) for group B, 73 % for group C, and 73 % for group D (95 % CI 0.34–1.40). Disease-free survival rates were consistent with progressionfree survival rates and were 81 % (95 % CI 72–88) for group A, 84 % (95 % CI 72–91) for group B, 80 % (95 % CI 70–86) for group C, and 75 % (95 % CI 64–83) for group D. In NeoALTTO trial patients who achieved pCR had longer progressionfree survival (85 % (95 % CI 76–91)) compared with patients who did not achieve pCR (76 % (95 % CI 71–81)).Conclusion. High levels of progression-free survival and disease-free survival at 5–10-years follow-up show large and overlapping CI, but support the primary endpoint (pCR) and suggest that neoadjuvant pertuzumab is beneficial when combined with trastuzumab and docetaxel. Additionally, they suggest that pCR could be an early indicator of long-term outcome in early-stage HER2-positive BC.https://ojrs.abvpress.ru/ojrs/article/view/1272her2-positive breast cancerstage ii–iiineoadjuvant double her2 blockadetrastuzumab + pertuzumablapatinib + trastuzumab
spellingShingle V. F. Semiglazov
N. B. Bekkeldieva
P. V. Krivorotko
A. V. Komyakhov
R. M. Paltuev
A. I. Tseluyko
L. P. Gigolaeva
T. T. Tabagua
E. K. Zhiltsova
V. S. Apollonova
G. A. Dashyan
A. G. Kudaybergenova
V. G. Ivanov
A. A. Bozhok
D. G. Ulrikh
A. O. Gorina
T. Yu. Semiglazova
Improving treatment outcomes for patients with HER2‑positive breast cancer using neoadjuvant double HER2 blockade
Опухоли женской репродуктивной системы
her2-positive breast cancer
stage ii–iii
neoadjuvant double her2 blockade
trastuzumab + pertuzumab
lapatinib + trastuzumab
title Improving treatment outcomes for patients with HER2‑positive breast cancer using neoadjuvant double HER2 blockade
title_full Improving treatment outcomes for patients with HER2‑positive breast cancer using neoadjuvant double HER2 blockade
title_fullStr Improving treatment outcomes for patients with HER2‑positive breast cancer using neoadjuvant double HER2 blockade
title_full_unstemmed Improving treatment outcomes for patients with HER2‑positive breast cancer using neoadjuvant double HER2 blockade
title_short Improving treatment outcomes for patients with HER2‑positive breast cancer using neoadjuvant double HER2 blockade
title_sort improving treatment outcomes for patients with her2 positive breast cancer using neoadjuvant double her2 blockade
topic her2-positive breast cancer
stage ii–iii
neoadjuvant double her2 blockade
trastuzumab + pertuzumab
lapatinib + trastuzumab
url https://ojrs.abvpress.ru/ojrs/article/view/1272
work_keys_str_mv AT vfsemiglazov improvingtreatmentoutcomesforpatientswithher2positivebreastcancerusingneoadjuvantdoubleher2blockade
AT nbbekkeldieva improvingtreatmentoutcomesforpatientswithher2positivebreastcancerusingneoadjuvantdoubleher2blockade
AT pvkrivorotko improvingtreatmentoutcomesforpatientswithher2positivebreastcancerusingneoadjuvantdoubleher2blockade
AT avkomyakhov improvingtreatmentoutcomesforpatientswithher2positivebreastcancerusingneoadjuvantdoubleher2blockade
AT rmpaltuev improvingtreatmentoutcomesforpatientswithher2positivebreastcancerusingneoadjuvantdoubleher2blockade
AT aitseluyko improvingtreatmentoutcomesforpatientswithher2positivebreastcancerusingneoadjuvantdoubleher2blockade
AT lpgigolaeva improvingtreatmentoutcomesforpatientswithher2positivebreastcancerusingneoadjuvantdoubleher2blockade
AT tttabagua improvingtreatmentoutcomesforpatientswithher2positivebreastcancerusingneoadjuvantdoubleher2blockade
AT ekzhiltsova improvingtreatmentoutcomesforpatientswithher2positivebreastcancerusingneoadjuvantdoubleher2blockade
AT vsapollonova improvingtreatmentoutcomesforpatientswithher2positivebreastcancerusingneoadjuvantdoubleher2blockade
AT gadashyan improvingtreatmentoutcomesforpatientswithher2positivebreastcancerusingneoadjuvantdoubleher2blockade
AT agkudaybergenova improvingtreatmentoutcomesforpatientswithher2positivebreastcancerusingneoadjuvantdoubleher2blockade
AT vgivanov improvingtreatmentoutcomesforpatientswithher2positivebreastcancerusingneoadjuvantdoubleher2blockade
AT aabozhok improvingtreatmentoutcomesforpatientswithher2positivebreastcancerusingneoadjuvantdoubleher2blockade
AT dgulrikh improvingtreatmentoutcomesforpatientswithher2positivebreastcancerusingneoadjuvantdoubleher2blockade
AT aogorina improvingtreatmentoutcomesforpatientswithher2positivebreastcancerusingneoadjuvantdoubleher2blockade
AT tyusemiglazova improvingtreatmentoutcomesforpatientswithher2positivebreastcancerusingneoadjuvantdoubleher2blockade