Russian multicenter experience of using talazoparib in the treatment of patients with BRCA-associated metastatic breast cancer
Introduction. The presence of a germinal BRCA mutation occurs in 3–4% of all breast cancer (BC) patients with various biological subtypes, but significantly with a high frequency in patients with a triple negative biological subtype (in 10–20% of cases). For the treatment of patients with HER2-negat...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | Russian |
| Published: |
Remedium Group LLC
2020-12-01
|
| Series: | Медицинский совет |
| Subjects: | |
| Online Access: | https://www.med-sovet.pro/jour/article/view/5937 |
| _version_ | 1797841965307396096 |
|---|---|
| author | T. Yu. Semiglazova E. V. Lubennikova L. V. Bolotina R. V. Orlova F. V. Moiseenko A. V. Avramenko E. V. Artemeva S. A. Borozdina A. A. Vakhitova N. M. Volkov I. P. Ganshina Sh. A. Dzhalilova L. G. Zhukova B. S. Kasparov A. A. Kachmazov V. V. Klimenko A. i. Kornietskaya A. A. Meshcheryakov A. A. Paichadze A. N. Poltoratsky O. E. Ryabishina M. L. Stepanova E. N Imyanitov |
| author_facet | T. Yu. Semiglazova E. V. Lubennikova L. V. Bolotina R. V. Orlova F. V. Moiseenko A. V. Avramenko E. V. Artemeva S. A. Borozdina A. A. Vakhitova N. M. Volkov I. P. Ganshina Sh. A. Dzhalilova L. G. Zhukova B. S. Kasparov A. A. Kachmazov V. V. Klimenko A. i. Kornietskaya A. A. Meshcheryakov A. A. Paichadze A. N. Poltoratsky O. E. Ryabishina M. L. Stepanova E. N Imyanitov |
| author_sort | T. Yu. Semiglazova |
| collection | DOAJ |
| description | Introduction. The presence of a germinal BRCA mutation occurs in 3–4% of all breast cancer (BC) patients with various biological subtypes, but significantly with a high frequency in patients with a triple negative biological subtype (in 10–20% of cases). For the treatment of patients with HER2-negative metastatic breast cancer associated with gBRCA mutation, the effectiveness of biologically targeted drugs from the group of PARP inhibitors (olaparib and talazoparib) has been proven.Purpose. Comparison of the results of our experience with the use of talazoparib in patients with HER2-gBRCA+ + mBC with the data of the EMBRACA registration study.Materials and methods. As part of the multicenter compassionate use program (CUP) with the support of Pfizer, 24 patients with HER2-negative metastatic gBRCA-associated mutation metastatic breast cancer (HER2-gBRCA+ breast cancer) received biologically targeted therapy with the PARP inhibitor talazoparib at a standard oral dose of 1 mg per day for vital indications . The average age of patients with HER2-gBRCAm+ breast cancer was 50 years (29–90 years).Results. Objective response (OR) was registered in 29% of cases, disease control (OR+stabilization) – in 71% of cases. The median progression-free survival (PFS) was 6.5 months (95% CI [3–10]). Objective response, disease control, and median PFS were evaluated depending on the biological subtype, the number of lines of previous therapy, and the presence of platinum-containing agents in the anamnesis.Objective response and disease control were evaluated depending on the biological subtype: in patients with ER+HER2-mBC versus patients with triple negative subtype, OR was 33% vs 22%, and disease control was 83% vs 61%, respectively. In the presence of < 3 vs ≥ 3 lines of therapy for metastatic disease in the anamnesis, OR was 31% vs 12.5%, disease control – 75% vs 50% of cases, respectively. In the presence or absence of platinum-containing agents in the anamnesis, OR was observed in 22% vs 33% of cases, and disease control – 67% vs 67%, respectively.In patients with the luminal subtype versus patients with the triple negative subtype, the PFS was 9 months vs 5 months, respectively (HR = 0.705; 95% CI [0.231–2.147]; p = 0.5208). Median PFS in the presence of <3 vs ≥3 lines of therapy for metastatic disease in the anamnesis was 9 months vs 4 months, respectively (HR = 4,216; 95% CI [1,334–13,327]; p = 0.0056). In the presence or absence of platinum-containing agents in previous lines of therapy 5 months vs 9.5 months, respectively (HR =1.484; 95% CI [0.48–4.582]; p = 0.4750).During the treatment with talazoparib adverse events of the 3rd-4th grades were observed in 5 patients (20,8%). These include moderate and severe anemia in 3 patients (12.5%), thrombocytopenia in 1 patient (4%), and neutropenia in 1 patient (4%). The majority of patients (79,5%), which received talazoparib, did not require dose adjustment. The need to reduce the dose to 0.75 mg was noted in 3 patients (12.5%), to 0.5 mg – in 2 patients (8%). Hemotransfusion was performed in 3 patients. For effective therapy safety management regular monitoring of blood parameters is necessary.Conclusion. Thus, targeted therapy with talazoparib is an effective treatment option for HER2-gBRCA+ mBC. |
| first_indexed | 2024-04-09T16:40:03Z |
| format | Article |
| id | doaj.art-4dfe72bac118488ca84b9c829b2faa84 |
| institution | Directory Open Access Journal |
| issn | 2079-701X 2658-5790 |
| language | Russian |
| last_indexed | 2024-04-09T16:40:03Z |
| publishDate | 2020-12-01 |
| publisher | Remedium Group LLC |
| record_format | Article |
| series | Медицинский совет |
| spelling | doaj.art-4dfe72bac118488ca84b9c829b2faa842023-04-23T06:56:44ZrusRemedium Group LLCМедицинский совет2079-701X2658-57902020-12-0102014314610.21518/2079-701X-2020-20-143-1495403Russian multicenter experience of using talazoparib in the treatment of patients with BRCA-associated metastatic breast cancerT. Yu. Semiglazova0E. V. Lubennikova1L. V. Bolotina2R. V. Orlova3F. V. Moiseenko4A. V. Avramenko5E. V. Artemeva6S. A. Borozdina7A. A. Vakhitova8N. M. Volkov9I. P. Ganshina10Sh. A. Dzhalilova11L. G. Zhukova12B. S. Kasparov13A. A. Kachmazov14V. V. Klimenko15A. i. Kornietskaya16A. A. Meshcheryakov17A. A. Paichadze18A. N. Poltoratsky19O. E. Ryabishina20M. L. Stepanova21E. N Imyanitov22Petrov National Medical Cancer Research Centre; North-Western State Medical University named after I.I. MechnikovBlokhin National Medical Research Center of OncologyHertsen Moscow Oncology Research InstituteSt Petersburg University; City Clinical Oncological DispensaryPetrov National Medical Cancer Research Centre; St Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncology)City Clinical Oncological DispensarySt Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncology)City Clinical Oncological DispensarySt Petersburg UniversitySt Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncology)Blokhin National Medical Research Center of OncologyPetrov National Medical Cancer Research CentreLoginov Moscow Clinical Scientific CenterPetrov National Medical Cancer Research CentreHertsen Moscow Oncology Research InstitutePetrov National Medical Cancer Research CentreHertsen Moscow Oncology Research InstituteBlokhin National Medical Research Center of OncologyHertsen Moscow Oncology Research InstitutePetrov National Medical Cancer Research CentreBlokhin National Medical Research Center of OncologySt Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncology)Petrov National Medical Cancer Research Centre; North-Western State Medical University named after I.I. MechnikovIntroduction. The presence of a germinal BRCA mutation occurs in 3–4% of all breast cancer (BC) patients with various biological subtypes, but significantly with a high frequency in patients with a triple negative biological subtype (in 10–20% of cases). For the treatment of patients with HER2-negative metastatic breast cancer associated with gBRCA mutation, the effectiveness of biologically targeted drugs from the group of PARP inhibitors (olaparib and talazoparib) has been proven.Purpose. Comparison of the results of our experience with the use of talazoparib in patients with HER2-gBRCA+ + mBC with the data of the EMBRACA registration study.Materials and methods. As part of the multicenter compassionate use program (CUP) with the support of Pfizer, 24 patients with HER2-negative metastatic gBRCA-associated mutation metastatic breast cancer (HER2-gBRCA+ breast cancer) received biologically targeted therapy with the PARP inhibitor talazoparib at a standard oral dose of 1 mg per day for vital indications . The average age of patients with HER2-gBRCAm+ breast cancer was 50 years (29–90 years).Results. Objective response (OR) was registered in 29% of cases, disease control (OR+stabilization) – in 71% of cases. The median progression-free survival (PFS) was 6.5 months (95% CI [3–10]). Objective response, disease control, and median PFS were evaluated depending on the biological subtype, the number of lines of previous therapy, and the presence of platinum-containing agents in the anamnesis.Objective response and disease control were evaluated depending on the biological subtype: in patients with ER+HER2-mBC versus patients with triple negative subtype, OR was 33% vs 22%, and disease control was 83% vs 61%, respectively. In the presence of < 3 vs ≥ 3 lines of therapy for metastatic disease in the anamnesis, OR was 31% vs 12.5%, disease control – 75% vs 50% of cases, respectively. In the presence or absence of platinum-containing agents in the anamnesis, OR was observed in 22% vs 33% of cases, and disease control – 67% vs 67%, respectively.In patients with the luminal subtype versus patients with the triple negative subtype, the PFS was 9 months vs 5 months, respectively (HR = 0.705; 95% CI [0.231–2.147]; p = 0.5208). Median PFS in the presence of <3 vs ≥3 lines of therapy for metastatic disease in the anamnesis was 9 months vs 4 months, respectively (HR = 4,216; 95% CI [1,334–13,327]; p = 0.0056). In the presence or absence of platinum-containing agents in previous lines of therapy 5 months vs 9.5 months, respectively (HR =1.484; 95% CI [0.48–4.582]; p = 0.4750).During the treatment with talazoparib adverse events of the 3rd-4th grades were observed in 5 patients (20,8%). These include moderate and severe anemia in 3 patients (12.5%), thrombocytopenia in 1 patient (4%), and neutropenia in 1 patient (4%). The majority of patients (79,5%), which received talazoparib, did not require dose adjustment. The need to reduce the dose to 0.75 mg was noted in 3 patients (12.5%), to 0.5 mg – in 2 patients (8%). Hemotransfusion was performed in 3 patients. For effective therapy safety management regular monitoring of blood parameters is necessary.Conclusion. Thus, targeted therapy with talazoparib is an effective treatment option for HER2-gBRCA+ mBC.https://www.med-sovet.pro/jour/article/view/5937metastatic breast cancerbrca mutationparp inhibitorstalazoparibobjective responsedisease controlprogression-free survivalanemiathrombocytopenia |
| spellingShingle | T. Yu. Semiglazova E. V. Lubennikova L. V. Bolotina R. V. Orlova F. V. Moiseenko A. V. Avramenko E. V. Artemeva S. A. Borozdina A. A. Vakhitova N. M. Volkov I. P. Ganshina Sh. A. Dzhalilova L. G. Zhukova B. S. Kasparov A. A. Kachmazov V. V. Klimenko A. i. Kornietskaya A. A. Meshcheryakov A. A. Paichadze A. N. Poltoratsky O. E. Ryabishina M. L. Stepanova E. N Imyanitov Russian multicenter experience of using talazoparib in the treatment of patients with BRCA-associated metastatic breast cancer Медицинский совет metastatic breast cancer brca mutation parp inhibitors talazoparib objective response disease control progression-free survival anemia thrombocytopenia |
| title | Russian multicenter experience of using talazoparib in the treatment of patients with BRCA-associated metastatic breast cancer |
| title_full | Russian multicenter experience of using talazoparib in the treatment of patients with BRCA-associated metastatic breast cancer |
| title_fullStr | Russian multicenter experience of using talazoparib in the treatment of patients with BRCA-associated metastatic breast cancer |
| title_full_unstemmed | Russian multicenter experience of using talazoparib in the treatment of patients with BRCA-associated metastatic breast cancer |
| title_short | Russian multicenter experience of using talazoparib in the treatment of patients with BRCA-associated metastatic breast cancer |
| title_sort | russian multicenter experience of using talazoparib in the treatment of patients with brca associated metastatic breast cancer |
| topic | metastatic breast cancer brca mutation parp inhibitors talazoparib objective response disease control progression-free survival anemia thrombocytopenia |
| url | https://www.med-sovet.pro/jour/article/view/5937 |
| work_keys_str_mv | AT tyusemiglazova russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT evlubennikova russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT lvbolotina russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT rvorlova russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT fvmoiseenko russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT avavramenko russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT evartemeva russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT saborozdina russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT aavakhitova russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT nmvolkov russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT ipganshina russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT shadzhalilova russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT lgzhukova russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT bskasparov russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT aakachmazov russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT vvklimenko russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT aikornietskaya russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT aameshcheryakov russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT aapaichadze russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT anpoltoratsky russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT oeryabishina russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT mlstepanova russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer AT enimyanitov russianmulticenterexperienceofusingtalazoparibinthetreatmentofpatientswithbrcaassociatedmetastaticbreastcancer |