SYSTEMIC THERAPY FOR ADVANCED OVARIAN CANCER IN BRCA1 MUTATION CARRIERS -NEW THERAPEUTIC APPROACHES: RESULTS OF A PROSPECTIVE NON-RANDOMIZED MULTI-CENTER STUDY


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Abstract

Background. BRCA1-associated tumors demonstrate a unique sensitivity to platinum-based drugs, but the overall effectiveness of treatment remains limited. Despite the pronounced regression of the tumor, standard therapy with platinum-based drugs rarely leads to complete pathomorphological response. Objective: to evaluate the clinical efficacy, safety, frequency of complete pathomorphological responses of the new scheme of neoadjuvant therapy for patients with BRCA1-associated ovarian cancer (OC) using combination of mitomycin C and cisplatin. Methods. The study included 217 patients with OC who were treated during 2015-2017. Three oncological centers participated in the study. All patients with OC were subjected to polymerase chain reaction testing for mutations: BRCA1 c.5266dupC [5382insC], c.4034delA [4153delA], c.181T>G [C61G], c.68_69delAG [185delAG] prior to initiation of treatment. Of the 217 patients, 21 (10%) mutation carriers were identified; 12 (57%) patients received a combination of mitomycin C 10 mg/m2 and cisplatin 100 mg/m2 every 4 weeks in the neoadjuvant regimen. The results of a prospective study of the NACT of BRCAI-associated OC using combination of mitomycin C and cisplatin were compared to the retrospective data (n=62) of NACT of BRCA1-associated OC treated with standard neoadjuvant therapy. Results. All 12 OC patients demonstrated an objective clinical response to treatment. Complete cytoreductive surgery was achieved in all patients included in the study. The pathological evaluation of tissues removed during surgery established a complete pathomorphological response (pCR) in 2 (17%) of 12 cases. In addition, one patient had a complete pathomorphological r esponse in the ovaries and an almost complete response in the omentum. In general, 5 (42%) patients had a pronounced pathomorphological response (score 3, according to [12]). Conclusion. The combination of platinum doublets in combination with other drugs, whose activity is not limited to cells with BRCA1 deficiency, can be a promising chemotherapeutic approach. The use of platinum-taxane regimens, which are the current «gold» standard, apparently does not exceed other regimens in effectiveness for BRCA1 gene mutations carriers.

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About the authors

T. V Gorodnova

N.N. Petrov National Medical Research Center of Oncology

Email: t.gorodnova@mail.ru
PhD, oncologisT., researcher of the Department of oncogynecology St. Petersburg, Russia

A. P Sokolenko

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

A. O Ivantsov

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

Kh. B Kotiv

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

M. G Yakovleva

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

O. N Mikheeva

Leningrad Regional Oncological Center

St. Petersburg, Russia

G. I Mikhaylyuk

Leningrad Regional Oncological Center

St. Petersburg, Russia

A. S Lisyanskaya

St. Petersburg State Healthcare Institution “City Clinical Oncology Center"; Pavlov First St. Petersburg State Medical University

St. Petersburg, Russia

K. D Guseinov

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

E. A Nekrasova

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

O. A Smirnova

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

A. A Sidoruk

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

N. E Bondarev

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

N. S Matveeva

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

I. E Meshkova

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

N. A Mikaya

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

S. V Petrik

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

G. M Manikhas

St. Petersburg State Healthcare Institution “City Clinical Oncology Center"; Pavlov First St. Petersburg State Medical University

St. Petersburg, Russia

S. A Protsenko

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

I. V Berlev

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

A. M Belyaev

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

E. N Imyanitov

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

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