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Russian multicenter experience of using talazoparib in the treatment of patients with BRCA-associated metastatic breast cancer

https://doi.org/10.21518/2079-701X-2020-20-143-149

Abstract

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.

About the Authors

T. Yu. Semiglazova
Petrov National Medical Cancer Research Centre; North-Western State Medical University named after I.I. Mechnikov
Russian Federation

Tatiana Yu. Semiglazova, Dr. of Sci. (Med.), Associate Professor, Head and Leading Research Associate of Scientific Department of Therapeutic Oncology and Rehabilitation Innovative Methods, Petrov National Medical Cancer Research Centre; Professor of Department of Oncology, North-Western State Medical University named after I.I. Mechnikov;

68, Leningradskaya St., Pesochnyy Settlement, St Petersburg, 197758, Russia; 
41, Kirochnaya St., St Petersburg, 191015, Russia


E. V. Lubennikova
Blokhin National Medical Research Center of Oncology
Russian Federation

Elena V. Lubennikova, Cand. of Sci. (Med.), Senior Research Associate, Cancer Drug Therapy (Chemotherapeutic) Department No. 3

24, Kashirskoye Shosse, Moscow, 115478, Russia


L. V. Bolotina
Hertsen Moscow Oncology Research Institute
Russian Federation

Larisa V. Bolotina, Dr. of Sci. (Med.), Head of Chemotherapy Unit

3, 2-y Botkinskiy Proezd, Moscow, 125284, Russia


R. V. Orlova
St Petersburg University; City Clinical Oncological Dispensary
Russian Federation

Rashida V. Orlova, Dr. of Sci. (Med.), Professor, Head of Department of Oncology, Faculty of Medicine, St Petersburg University; Chief Specialist in Clinical Oncology and Rehabilitation, City Clinical Oncological Dispensary

7–9, Universitetskaya Emb., St Petersburg, 199034, Russia;
56, Veteranov Ave., St Petersburg, 198255, Russia


F. V. Moiseenko
Petrov National Medical Cancer Research Centre; St Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncology)
Russian Federation

Fedor V. Moiseenko, Dr. of Sci. (Med.), Associate Professor, Research Associate, Scientific Department of Therapeutic Oncology and Rehabilitation Innovative Methods, Petrov National Medical Cancer Research Centre; Head of Chemotherapy Unit, St Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncology)

68, Leningradskaya St., Pesochnyy Settlement, St Petersburg, 197758, Russia; 
68a, Leningradskaya St., Pesochnyy Settlement, St Petersburg, 197758, Russia


A. V. Avramenko
City Clinical Oncological Dispensary
Russian Federation

Anna V. Avramenko, Oncologist, Head of Chemotherapy Unit No. 11

56, Veteranov Ave., St Petersburg, 198255, Russia


E. V. Artemeva
St Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncology)
Russian Federation

Elizaveta V. Artemeva, Oncologist, Chemotherapy Unit

68a, Leningradskaya St., Pesochnyy Settlement, St Petersburg, 197758, Russia


S. A. Borozdina
City Clinical Oncological Dispensary
Russian Federation

Sofya A. Borozdina, Oncologist

56, Veteranov Ave., St Petersburg, 198255, Russia


A. A. Vakhitova
St Petersburg University
Russian Federation

Almira A. Vakhitova, Postgraduate Student 

7–9, Universitetskaya Emb., St Petersburg, 199034, Russia


N. M. Volkov
St Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncology)
Russian Federation

Nikita M. Volkov, Cand. of Sci. (Med.), Head Officer of Departments of Chemotherapeutic and Radiotherapeutic Profile

68a, Leningradskaya St., Pesochnyy Settlement, St Petersburg, 197758, Russia


I. P. Ganshina
Blokhin National Medical Research Center of Oncology
Russian Federation

Inna P. Ganshina, Cand. of Sci. (Med.), Leading Research Associate, Cancer Drug Therapy (Chemotherapeutic) Department No. 3

24, Kashirskoye Shosse, Moscow, 115478, Russia


Sh. A. Dzhalilova
Petrov National Medical Cancer Research Centre
Russian Federation

Sheyla A. Dzhalilova, Oncologist, Clinical Diagnostic Department tment No. 3

68, Leningradskaya St., Pesochnyy Settlement, St Petersburg, 197758, Russia


L. G. Zhukova
Loginov Moscow Clinical Scientific Center
Russian Federation

Liudmila G. Zhukova, Dr. of Sci. (Med.), Professor of RAS, Deputy Director of Oncology

86, Entuziastov Shosse, Moscow, 111123, Russia


B. S. Kasparov
Petrov National Medical Cancer Research Centre
Russian Federation

Boris S. Kasparov, Cand. of Sci. (Med.), Oncologist, Head of Clinical Diagnostic Department, Research Associate of Scientific Department of Therapeutic Oncology and Rehabilitation Innovative Methods;

68, Leningradskaya St., Pesochnyy Settlement, St Petersburg, 197758, Russia

 


A. A. Kachmazov
Hertsen Moscow Oncology Research Institute
Russian Federation

Andrei A. Kachmazov, Junior Research Associate, Department of Medication-Based Tumour Treatment

3, 2-y Botkinskiy Proezd, Moscow, 125284, Russia


V. V. Klimenko
Petrov National Medical Cancer Research Centre
Russian Federation

Veronika V. Klimenko, Oncologist, Clinical Diagnostic Department, Research Associate of Scientific Department of Therapeutic Oncology and Rehabilitation Innovative Methods

68, Leningradskaya St., Pesochnyy Settlement, St Petersburg, 197758, Russia


A. i. Kornietskaya
Hertsen Moscow Oncology Research Institute
Russian Federation

Anna L. Kornietskaya, Cand. of Sci. (Med.), Senior Research Associate of Chemotherapy Unit, Department of Medication-Based Tumour Treatment

3, 2-y Botkinskiy Proezd, Moscow, 125284, Russia


A. A. Meshcheryakov
Blokhin National Medical Research Center of Oncology
Russian Federation

Andrey A. Meshcheryakov, Dr. of Sci. (Med.), Head of Cancer Drug Therapy (Chemotherapeutic) Department No. 3

24, Kashirskoye Shosse, Moscow, 115478, Russia

 


A. A. Paichadze
Hertsen Moscow Oncology Research Institute
Russian Federation

Anna  A.  Paichadze,  Cand. of Sci. (Med.), Research Associate of Chemotherapy Unit

3, 2-y Botkinskiy Proezd, Moscow, 125284, Russia


A. N. Poltoratsky
Petrov National Medical Cancer Research Centre
Russian Federation

Artem N. Poltoratsky, Cand. of Sci. (Med.), Oncologist, Head of Department of Preclinical and Clinical Studies

68, Leningradskaya St., Pesochnyy Settlement, St Petersburg, 197758, Russia


O. E. Ryabishina
Blokhin National Medical Research Center of Oncology
Russian Federation

Oksana E. Ryabishina (Med.), Oncologist, Cancer Drug Therapy (Chemotherapeutic) Department No. 3

24, Kashirskoye Shosse, Moscow, 115478, Russia


M. L. Stepanova
St Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncology)
Russian Federation

Maria L. Stepanova, Research Associate of Research Department

68a, Leningradskaya St., Pesochnyy Settlement, St Petersburg, 197758, Russia


E. N Imyanitov
Petrov National Medical Cancer Research Centre; North-Western State Medical University named after I.I. Mechnikov
Russian Federation

Evgeny N. Imyanitov, Corr. Member of RAS, Dr. of Sci. (Med.), Professor, Head of Scientific Department of Tumour Biology and Molecular Oncology Laboratory, Petrov National Medical Cancer Research Centre; Professor of Department of Oncology, North-Western State Medical University named after I.I. Mechnikov

68, Leningradskaya St., Pesochnyy Settlement, St Petersburg, 197758, Russia; 
41, Kirochnaya St., St Petersburg, 191015, Russia


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Review

For citations:

Semiglazova TY, Lubennikova EV, Bolotina LV, Orlova RV, Moiseenko FV, Avramenko AV, Artemeva EV, Borozdina SA, Vakhitova AA, Volkov NM, Ganshina IP, Dzhalilova SA, Zhukova LG, Kasparov BS, Kachmazov AA, Klimenko VV, Kornietskaya Ai, Meshcheryakov AA, Paichadze AA, Poltoratsky AN, Ryabishina OE, Stepanova ML, Imyanitov EN. Russian multicenter experience of using talazoparib in the treatment of patients with BRCA-associated metastatic breast cancer. Meditsinskiy sovet = Medical Council. 2020;(20):143-146. (In Russ.) https://doi.org/10.21518/2079-701X-2020-20-143-149

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