Papers by Alexey Manikhas
Opuholi ženskoj reproduktivnoj sistemy, 2016
Трижды негативный рак молочной железы (РМЖ)-крайне агрессивная форма злокачественных опухолей мол... more Трижды негативный рак молочной железы (РМЖ)-крайне агрессивная форма злокачественных опухолей молочной железы с высоким уровнем метастазирования, частым возникновением рецидивов и низкой выживаемостью по сравнению с другими подтипами РМЖ. Цель исследования-разработка и внедрение в клиническую практику ГКОД оптимизированной тактики лечения больных трижды негативным РМЖ. Материалы и методы. В исследование была включена 201 пациентка (21-90 лет, средний возраст 52 года), проходившая лечение в первом отделении Санкт-Петербургского ГКОД в период с 2005 по 2011 г. У всех пациенток до начала лечения был верифицирован инвазивный РМЖ IА-IIIC стадии с тройным негативным фенотипом по данным иммуногистохимического (ИГХ) исследования опухолевого материала. В качестве неоадъювантного режима проводилась стандартная химиотерапия по схемам FAC, CMF и таксансодержащей схеме. Степень лечебного патоморфоза оценивали согласно классификации Miller-Payne (2003), которая была разработана с учетом показателей общей выживаемости пациенток в зависимости от степени патоморфологической регрессии опухоли. Результаты. Проведена оценка 3-летней безрецидивной выживаемости в зависимости от степени достижения патоморфологического регресса и степени гистологической злокачественности. Прослеживается четкая зависимость 3-летней БРВ от степени гистологической дифференцировки опухоли. Прослежена обратная корреляция высокой степени гистологической злокачественности с коротким безрецидивным периодом. Заболевание прогрессировало у больных, имеющих высокую степень гистологической злокачественности. Заключение. Наибольшей эффективности удалось достичь у пациенток, получающих химиотерапевтическое лечение с добавлением таксанов. Пациенткам, имеющим высокую степень гистологической злокачественности, целесообразно назначение таксансодержащих режимов химиотерапии.
BMC Cancer, Jan 31, 2023
Background The TROIKA trial established that HD201 and trastuzumab were equivalent in terms of pr... more Background The TROIKA trial established that HD201 and trastuzumab were equivalent in terms of primary endpoints (total pathological complete response) following neoadjuvant treatment. The objective of the present analysis was to compare survival outcomes and final safety. Methods In the TROIKA trial, patients with ERBB2-positive early breast cancer were randomized and treated with either HD201 or the referent trastuzumab. Eligible patients received 8 cycles of either HD201 or referent trastuzumab (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) every 3 weeks in combination with 8 cycles of chemotherapy (4 cycles of docetaxel, 75 mg/m 2 , followed by 4 cycles of epirubicin, 75 mg/m 2 , and cyclophosphamide, 500 mg/m 2) in the neoadjuvant setting. The patients then underwent surgery followed by 10 cycles of adjuvant HD201 or referent trastuzumab according to their initial randomization to complete one year of trastuzumab-directed therapy. Eventfree and overall survival rates were calculated using Kaplan-Meier analysis. The hazard ratio for event-free survival was estimated by Cox proportional hazards regression. Results The final analysis was performed after all patients completed the study at a median follow-up of 37.7 months (Q1-Q3, 37.3-38.1 months). A total of 502 randomized patients received either HD201 or the referent trastuzumab, and 474 (94.2%) were eligible for inclusion in the per-protocol set. In this population, the 3-year event-free survival rates were 85.6% (95% CI: 80.28-89.52) and 84.9% (95% CI: 79.54-88.88) in the HD201 and referent trastuzumab groups, respectively (log rank p = 0.938) (HR 1.02, 95% CI: 0.63-1.63; p = 0.945). The 3-year overall survival rates were comparable between the HD201 (95.6%; 95% CI: 91.90-97.59) and referent trastuzumab treatment groups (96.0%, 95% CI: 92.45-97.90) (log rank p = 0.606). During the posttreatment follow-up period, adverse events were reported for 64 (27.4%) and 72 (29.8%) patients in the HD201 and the reference trastuzumab groups, respectively. Serious adverse events were rare and none of which were related to the study treatment. Conclusions This final analysis of the TROIKA trial further confirms the comparable efficacy and safety of HD201 and trastuzumab.
Journal of Clinical Oncology, May 20, 2013
517 Background: M in combination with T has shown promising activity and cardiac safety in MBC pa... more 517 Background: M in combination with T has shown promising activity and cardiac safety in MBC patients (pts). We conducted a randomized Phase III trial of first-line M plus T and P (MTP) versus T plus P (TP) in HER2+ MBC pts. Methods: Pts with HER2+ (by FISH) MBC ≥ 18 years and ECOG 0-1, who had received no prior chemotherapy for metastatic disease, were eligible. Left ventricular ejection fraction should be within normal institutional limits. Prior (neo-) adjuvant anthracyclines, T or P were permitted, if completed >1 year before the start of the study. Pts received M 50 mg/m2 q3w for 6 cycles, T 4 mg/kg loading dose followed by 2 mg/kg qw, and P 80 mg/m2qw, or T+P at the same doses until progression or toxicity. Primary outcome was progression-free survival (PFS). Enrollment of 332 pts would provide 80% power with a 5% significance to detect an improvement in PFS with MTP, assuming a median PFS of 8 months in TP and a hazard ratio (HR) of 0.70. Results: 363 pts enrolled (MTP 181, TP 183), 360 received treatment. The two groups were well balanced for demographics, pretreatment characteristics and extent of disease. One third of the pts had prior exposure to anthracyclines, but almost none to trastuzumab (1% and 2% in MTP and TP arms, respectively). Six cycles of M could be given to 72% of the pts. With a median follow-up of 31 months, median PFS was 16.1 and 14.5 months with MTP and TP, respectively (HR 0.84, P=0.174). In pts with ER and PR-negative tumors, PFS was 20.7 and 14.0 months, respectively (HR, 0.68; 95% CI 0.47–0.99). Median overall survival (OS) was 33.6 and 28.9 months, respectively (HR, 0.79, P=0.083). In ER and PR-negative tumors, OS was 38.2 and 27.9 months, respectively (HR, 0.63; 95% CI 0.42–0.93). The incidence of NYHA Class III/IV congestive heart failure was 3% with MTP and there were 2 cardiac deaths with TP. The frequency of adverse events was higher with MTP, especially myelosuppression, stomatitis and gastrointestinal intolerance. Conclusions: The trial failed to demonstrate a significant clinical improvement with the addition of M to TP. The clinical benefit observed in an exploratory analysis in the ER and PR-negative population deserves consideration for further clinical trials. Clinical trial information: NCT00294996.
Journal of Clinical Oncology, Jun 10, 2022
Tumors of female reproductive system, 2022
Background. Triple negative breast cancer has no specific treatment sites for chemotherapy and is... more Background. Triple negative breast cancer has no specific treatment sites for chemotherapy and is unfavorable in terms of prognosis. One of the drugs widely used in this cohort of patients is eribulin, which in addition to its antimitotic effect has an effect on the tumor microenvironment. The search for biological criteria that will allow predicting the effectiveness of the drug is assumed relevant since it will help to select patients who may receive the most benefit from certain therapy regimens.Objective: identification of immunological predictors of the therapeutic effectiveness of eribulin in patients with locally advanced or metastatic triple-negative breast cancer.Materials and methods. The study included 20 patients with locally advanced and metastatic triple negative breast cancer. 50 % had a short-term response (progression-free survival <3 months) to eribulin therapy, and 50 % had a long-term response (progression-free survival >6 months). Seven-color immunofluores...
Относительно недавно неоадъювантная эндокринотерапия стала рассматриваться как привлекательная ал... more Относительно недавно неоадъювантная эндокринотерапия стала рассматриваться как привлекательная альтернатива химиотерапевтическому лечению у постменопаузальных пациенток с крупными или неоперабельными ЭР-положительными опухолями. И хотя на сегодняшний день не было проведено крупных рандомизированных исследований, сравнивающих результаты только хирургического лечения и неоадьювантной эндокринотерапии с последующим хирургическим вмешательством, ряд исследований ингибиторов ароматазы (ИА) продемонстрировал обнадеживающие результаты. В нескольких крупных исследованиях проводилось сравнение различных ингибиторов ароматазы и тамоксифена. Одним из основных конечных результатов, по которым проводилась оценка эффективности лечения, являлась частота выполнения органосохраняюшего лечения.
Medical Council, 2017
The HannaH study showed that neoadjuvante-adjuvant subcutaneous and intravenous trastuzumab have ... more The HannaH study showed that neoadjuvante-adjuvant subcutaneous and intravenous trastuzumab have similar efficacy and tolerability in patients with early HER2-positive breast cancer. The analysis of the results of the subcutaneous and intravenous trastuzumab usage in Russian population showed the favorable association between tpCR anf EFS. tpCR achiviement is associated with clinical benefit in HER2 positive breast cancer. For patients with difficult venous access who do not require intravenous chemotherapy currently, Subcutaneous trastuzumab allows to receive effective treatment without the risk of complications, which involves catheterization of a Central vein.
BioDrugs
Background The Phase 3 CT-P6 3.2 study demonstrated equivalent efficacy and comparable safety bet... more Background The Phase 3 CT-P6 3.2 study demonstrated equivalent efficacy and comparable safety between CT-P6 and reference trastuzumab in patients with human epidermal growth factor receptor-2 (HER2)-positive early breast cancer after up to 3 years' follow-up. Objective To investigate long-term survival with CT-P6 and reference trastuzumab. Methods In the CT-P6 3.2 study, patients with HER2-positive early breast cancer were randomised to neoadjuvant chemotherapy with CT-P6 or reference trastuzumab, surgery, and adjuvant CT-P6 or reference trastuzumab before a 3-year posttreatment follow-up. Patients who completed the study could enter a 3-year extension (CT-P6 4.2 study). Data were collected every 6 months to assess overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). Results Of 549 patients enrolled in the CT-P6 3.2 study, 216 (39.3%) patients continued in the CT-P6 4.2 study (CT-P6, 107; reference trastuzumab, 109) (intention-to-treat extension set). Median follow-up was 76.4 months for both groups. Medians were not reached for time-to-event parameters; estimated hazard ratios (95% confidence intervals) for CT-P6 versus reference trastuzumab were 0.59 (0.17-2.02) for OS, 1.07 (0.50-2.32) for DFS, and 1.08 (0.50-2.34) for PFS. Corresponding 6-year survival rates in the CT-P6 and reference trastuzumab groups, respectively, were 0.
Annals of Oncology, 2012
Background: Good clinical judgement remains the best tool in determining a therapeutic plan; howe... more Background: Good clinical judgement remains the best tool in determining a therapeutic plan; however this process has become easier, and more reproducible with the ongoing progression of decision-making adjuncts such as: Nottingham Prognostic Index (NPI), which incorporates pathological features; Adjuvant! Online (AO), which incorporates clinic-pathological features; and Oncotype Dx ® Recurrence Score (RS) assay, which incorporates genetic features. We herein report our experience with the use of these tools, and their potential impact on chemotherapy uptake for patients in MWRH, Limerick, Ireland. Methods: Study period: 01/09/2008-31/12/2012. Data was derived from (1) MWCC Oncology database (2) pathology reports (3) patient files (4) RS assay reports. Data was collated and entered into an Access database and exported into SPSS (v.18) for analysis. Results Seventy-seven (77) patients with early stage endocrine positive breast cancer were analysed. Median age: 55.9 years (range: 30.6-72.3 years). Median follow-up: 20.9 months. Findings are shown below in tabular form. Conclusions: Chemotherapy uptake from the decision-making tools was varied within the cohort, but it was uniformly noted that patients were more likely to undertake chemotherapy if they had higher indices derived from these DMT, except in cases where the patients declined therapy, or if physicians' preference differed on clinical grounds. This highlights that none of the available DMT are perfect in isolation, but when used in concert, they can elucidate the best potential treatment pathway following consultation between patients and their healthcare providers; this is given by the fact that they all rely on different subsets of information to predict potential outcome. Further work is needed to find an algorithm that can appropriately incorporate these DMT any potential patient's best interest. Disclosure: All authors have declared no conflicts of interest.
European Journal of Cancer, 2018
The Breast, 2017
assessed. 66 (46%) pts were ER/PR-positive, 46 (32%)triplenegative, 31 (22%)-HER2-positive (in co... more assessed. 66 (46%) pts were ER/PR-positive, 46 (32%)triplenegative, 31 (22%)-HER2-positive (in combination with trastuzumab). Most of the pts (78%) had visceral mts (9 pts (6,3%) had a brain mts), a median number metastatic disease regions was 2 (1-3). Eribulin was administered as the 1st, 2nd and 3rd lines of MBC treatment to 62 (55,5%) pts, the 4th and later linesto 50 (44,5%) pts in HER2-negative group (n = 112). ORR and SD was 78% among HR-positive patients and 57% among TNMBC patients. Median PFS was 4,74 months (95% CI 2,61-8,01) among HR-positive and 3,0 months (95% CI 1,91-5,87) among TNMBC (p = 0,027). 28 pts (19,5%) treated with eribulin 8 months and longer (1 pt 40 cycles and continuous treatment). Tolerability of the drug was good: Withdrawn due to toxicity had 3,5%, dose reduction-16% of pts. The most common type of toxicity was hematological with neutropenia Gr I-II in 30 (21%) of pts and Gr III-IVin 18 (12,6%) of pts. Peripheral neuropathy Gr II was observed in 11 (8%) of pts. Conclusions: This is the real-life description of clinical outcomes, for patients initiating eribulin therapy for MBC throughout the Russian Federation. Our experience with eribulin in MBC patients confirms eribulin efficacy and safety in HER2-negative patients, the most effectiveness was in HR-positive group.
Voprosy onkologii, 2015
In the randomized phase 2 study there was evaluated the efficacy of neoadjuvant endocrine treatme... more In the randomized phase 2 study there was evaluated the efficacy of neoadjuvant endocrine treatment (anastrozole, exemestane) in comparison with chemotherapy (doxorubicin plus paclitaxel). Preoperative endocrine therapy was well tolerated. There was a trend towards higher overall rates of objective response and breast conserving surgery (BCS) among patients with tumors expressing high levels of ER (luminal A) in endocrine therapy group compared with chemotherapy group (43% vs 24%; p = 0,054). In HER2-positive breast cancer patients the addition of trastuzumab to neoadjuvant chemotherapy improved the overall and pathological complete response. Trastuzumab made possible an increasing number of breast conserving surgery (23% vs 13%; p = 0,022). No patient treated with trastuzumab and with chemotherapy had a local recurrence after BCS.
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 2014
Patients with HER2-positive early breast cancer (EBC) preferred subcutaneous (s.c.) trastuzumab, ... more Patients with HER2-positive early breast cancer (EBC) preferred subcutaneous (s.c.) trastuzumab, delivered via single-use injection device (SID), over the intravenous (i.v.) formulation (Cohort 1 of the PrefHer study: NCT01401166). Here, we report patient preference, healthcare professional satisfaction, and safety data pooled from Cohort 1 and also Cohort 2, where s.c. trastuzumab was delivered via hand-held syringe. Patients were randomized to receive four adjuvant cycles of 600 mg fixed-dose s.c. trastuzumab followed by four cycles of standard i.v. trastuzumab, or vice versa. The primary endpoint was overall preference proportions for s.c. or i.v., assessed by patient interviews in the evaluable ITT population. A total of 245 patients were randomized to receive s.c. followed by i.v. and 243 received i.v. followed by s.c. (evaluable ITT populations: 235 and 232 patients, respectively). s.c. was preferred by 415/467 [88.9%; 95% confidence interval (CI) 85.7-91.6; P < 0.0001; two...
The Breast, 2021
Background: Trastuzumab-dkst is a biosimilar of trastuzumab. The phase 3 HERITAGE trial demonstra... more Background: Trastuzumab-dkst is a biosimilar of trastuzumab. The phase 3 HERITAGE trial demonstrated equivalent overall response rate (ORR) with trastuzumab-dkst or originator trastuzumab at 24 weeks in patients with HER2-positive metastatic breast cancer receiving chemotherapy. We now present the correlation of ORR with progression-free survival (PFS) for maintenance monotherapy with trastuzumabdkst vs trastuzumab at 48 weeks of treatment, and the safety, tolerability, and immunogenicity. Methods: HERITAGE is a multicenter, double-blind, randomized, parallel-group, phase 3 study. Patients were randomized 1:1 to receive trastuzumab-dkst or trastuzumab in combination with taxane followed by continued monotherapy until disease progression. The analysis included PFS at 48 weeks to support the primary efficacy endpoint of ORR and safety, tolerability, and immunogenicity of trastuzumab-dkst vs trastuzumab as maintenance monotherapy. Results: Of 500 randomized patients, 342 entered the monotherapy phase; 214 patients received 48 weeks of treatment. There were no statistically significant differences between PFS, ORR, or interim
Linfield College Libraries Library, Oct 11, 2017
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Papers by Alexey Manikhas