Experience with olaparib in a patient with luminal HER2-positive metastatic breast cancer

Hereditary breast cancer (BC) accounts for about 5-10% of cases. BRCA-associated tumors have been identified as a separate group of malignant neoplasms with distinctive clinical manifestations and specific treatment features. Understanding of biological mechanisms leading to cancer in BRCA1/2 mutation carriers and discovery of potential molecular targets, such as poly (ADP-ribose) polymerase (PARP), involved in base excision repair mechanisms, led to the development of a new class of targeted drugs belonging to the PARP inhibitors group. PARP inhibition leads to the preservation of single-stranded DNA breaks, the arrest of the replication fork, and the realization of the “synthetic lethality” phenomenon due to the inability to repair double-stranded DNA breaks by homologous recombination in cells with mutations in the BRCA1/2 genes. Two randomized trials OlympiAD and EMBRACA evaluated and proved the effectiveness of PARP inhibitors in patients with metastatic BRCA-mutated HER2-negative breast cancer in comparison with standard chemotherapy. At the same time, data on the potential use of PARP inhibitors for the treatment of BRCA-mutated HER2-positive breast cancer patients are extremely limited. This article presents a clinical example of the use of olaparib in a patient with BRCA-mutated HER2-positive metastatic breast cancer

ПРЕДВАРИТЕЛЬНАЯ ОЦЕНКА ЭФФЕКТИВНОСТИ КОМБИНИРОВАННОГО ЛЕЧЕНИЯ С ВКЛЮЧЕНИЕМ HIFU-ТЕРАПИИ У БОЛЬНЫХ РАКОМ ПОДЖЕЛУДОЧНОЙ ЖЕЛЕЗЫ

 Purpose: to conduct a preliminary analysis of the safety and effectiveness of hifu-therapy with a lowenergy hifu-2001 device (shenzhen Huikang Medical apparatus Co., ltd) performed concurrently with chemotherapy in pancreatic cancer patients who are not suitable for surgery or chemoradiotherapy.Material and Method. The study included 24 pancreatic cancer patients who were treated at the Hertsen Moscow Oncology Research institute in the period from 2016 to 2019. There were 17 (71 %) women and 7 (29 %) men. The percentage of patients in the elderly group was 79 %. Stage iia pancreatic cancer was diagnosed in 3 (12.5 %) patients, stage ii in 5 (21 %) patients, stage iii in 9 (37.5 %) patients, and stage iv in 7 (29 %) patients. All patients received combination therapy, including systemic chemotherapy and hifu-therapy. Results. The most frequent adverse events of treatment were skin burns (n=6), with third-degree burns occurring in 2 (8.3 %) patients. Local sclerosis of subcutaneous adipose tissue was observed in 4 (17 %) patients; development of asymptomatic pancreatic pseudocysts in the area of hifu exposure was observed in 1 (4 %) patient. Pain control was achieved in 17 (85 %) patients, and local tumor control was achieved in 19 (79.2 %) patients. The follow-up time ranged from 5 to 30 months with a median time of 14.5 months. The median total life expectancy of patients was 16 months, and the median time to progression was 9 months. The overall 6-month survival rate was 100 %. The 1- and 1.5-year survival rates were 75.0 % and 41.7 %, respectively. The 2-year survival rate was 17.2 %. The 6-month and 1-year disease-free survival rates were 62.5 % and 12.5 %, respectively. Conclusion. The short- and long-term outcomes were consistent with those described in other studies, which indicated that a combination of systemic drug therapy and hifu-therapy is an appropriate approach for the treatment of patients with pancreatic cancer. Целью исследования является предварительный анализ безопасности и эффективности применения HiFu-терапии на низкоэнергетическом аппарате HiFu-2001 (shenzhen Huikang Medical apparatus Co., ltd) на фоне специфической лекарственной терапии у больных раком поджелудочной железы, не подлежащих хирургическому или химиолучевому лечению. Материал и методы. В исследование включено 24 больных раком поджелудочной железы, получавших лечение на базе МниОи им. П.А. Герцена в период с 2016 по 2019 г., из них 17 (71 %) женщин и 7 (29 %) мужчин. Доля пациентов, входящих в возрастные группы пожилого и старческого возраста, составила 79 %. Рак поджелудочной железы iiА стадии диагностирован у 3 (12,5 %) пациентов, iiВ стадии – у 5 (21 %), iii стадии – у 9 (37,5 %), iV стадии – у 7 (29 %) больных. Всем пациентам проводилась комбинированная терапия, включающая системную химиотерапию и HiFu-терапию. Результаты. наиболее частыми нежелательными явлениями  течения являлись ожоги кожи (n=6), в том числе iii степени – у 2 (8,3 %) пациентов. локальный склероз подкожной жировой клетчатки был отмечен у 4 (17 %); развитие бессимптомной псевдокисты поджелудочной железы в области HiFu воздействия – у 1 (4 %) пациента. контроль болевого синдрома был достигнут у 17 (85 %), локальный контроль опухоли – у 19 (79,2 %) больных. Сроки наблюденияза пациентами составили 5–30 мес с медианой – 14,5 мес. Медиана общей продолжительности жизни пациентов составила 16 мес, медиана времени до прогрессирования – 9 мес. Общая 6-месячная выживаемость составила 100,0 %, 1-летняя – 75,0 %, 1,5-летняя – 41,7 %, 2-летняя – 17,2 %. Полугодовая выживаемость без прогрессирования равнялась 62,5 %, 1-летняя – 12,5 %. Заключение. Полученные ближайшие и отдаленные результаты являются сопоставимыми с ранее описанными в международной клинической практике, кроме того, они демонстрируют перспективность использования  комбинации системной лекарственной терапии и локального термического воздействия у больных раком  поджелудочной железы и дальнейшего изучения ее эффективности.

Эффективность и безопасность винфлунина во 2-й линии терапии у больных распространенным переходно-клеточным раком мочевых путей в клинической практике

Objective: to investigate the safety of vinflunine, the rate and duration of its treatment response, progression-free and overall survival rates in patients receiving this drug in routine clinical practice for first-line chemotherapy (CT) – resistant disseminated transitional cell carcinoma of the urinary tract.Materials and methods. This retrospective observational multicenter study included data on 25 patients with verified disseminated transitional cell carcinoma of the urinary tract who took vinflunine for tumor progression after first-line CT performed in 11 Russian clinical centers in 23 March 2013 to 26 June 2016. The median age of the patients was 60 (44‒81) years. Their baseline somatic status was rated as ECOG 0 in 1 (4.0 %) patient, ECOG 1 in 13 (52.0 %) patients, EGOG 2 in 9 (36.0 %), and ECOG 3 in 2 (8.0 %). The most common sites of tumor foci were bones (n = 14, 56.0 %), lymph nodes of different groups (n = 14; 56.0 %), and lung (n = 9; 36.0 %).Results. Adverse reactions were recorded in 24 (96.0 %) cases. The most common types of toxicity were asthenia (n = 19; 76.0 %), anemia (n = 18; 72.0 %), neutropenia (n = 13; 52 %), and nausea (n = 12; 48.0 %). Most adverse events were grades I–II and well controlled. There were no deaths due to adverse events. The best treatment response was regarded as partial in 6 (24.0 %) patients; stabilization and progression were observed in 10 (40.0 %) and 9 (36.0 %) patients, respectively. The median duration of partial response was 5.1 (95 % confidence interval (CI), 0.6–15.0) months; that of stabilization was 3.4 (95 % CI, 1.2–6.3) months. In all the 25 cases, the median progression-free and overall survival rates were 3.7 (95 % CI, 2.1‒5.3) and 6.5 (95 % CI, 5.2‒7.8) months, respectively. The somatic status was a predictor of overall survival (p < 0.0001).Conclusion. The efficacy and safety of vinflunine in second-line therapy for first-line CT-resistant disseminated transitional cell carcinoma of the urinary tract in unselected patients agree with those previously observed in Phase III randomized trial.Цель исследования – изучение безопасности, частоты и длительности ответов, беспрогрессивной и общей выживаемости у больных, получавших винфлунин в рутинной клинической практике по поводу распространенного переходно-клеточного рака мочевых путей, резистентного к 1-й линии химиотерапии (ХТ).Материалы и методы. В ретроспективное наблюдательное многоцентровое исследование включены данные 25 больных верифицированным распространенным переходно-клеточным раком мочевых путей, получавших винфлунин по поводу прогрессии опухоли после проведения ХТ 1-й линии с 23.03.2013 по 26.06.2016 в 11 клинических центрах России. Медиана возраста – 60 (44–81) лет. Исходный соматический статус по шкале ECOG был расценен как 0 у 1 (4,0 %), 1 – у 13 (52,0 %), 2 – у 9 (36,0 %), 3 – у 2 (8,0 %) больных. Наиболее распространенными локализациями опухолевых очагов были кости (n =14; 56,0 %), лимфатические узлы различных групп (n =14; 56,0 %) и легкие (n = 9; 36,0 %).Результаты. Нежелательные явления были зарегистрированы в 24 (96,0 %) случаях. Наиболее распространенными видами токсичности являлись астения (n =19; 76,0 %), анемия (n =18; 72,0 %), нейтропения (n =13; 52,0 %), тошнота (n = 12; 48,0 %). Нежелательные явления в большинстве наблюдений имели I–II степени тяжести и хорошо контролировались. Смертности, обусловленной нежелательными явлениями, не зарегистрировано. Наилучший ответ на лечение расценен как частичный у 6 (24,0 %), стабилизация – у 10 (40,0 %), прогрессирование – у 9 (36,0 %) больных. Медиана длительности частичного ответа составила 5,1 (95 % доверительный интервал (ДИ) 0,6–15,0) мес, стабилизации – 3,4 (95 % ДИ 1,2–6,3) мес. Медиана беспрогрессивной и общей выживаемости всех 25 больных составила 3,7 (95 % ДИ 2,1–5,3) и 6,5 (95 % ДИ 5,2–7,8) мес соответствен- но. Соматический статус являлся фактором прогноза общей выживаемости (p < 0,0001).Заключение. Эффективность и безопасность применения винфлунина во 2-й линии терапии распространенного переходно-клеточного рака мочевых путей, резистентного к 1-й линии ХТ, у неотобранных больных соответствуют ранее полученным результатам рандомизированного исследования III фазы.

First-line chemotherapy for head and neck squamous cell carcinoma. Optimal strategy

The study objective is to provide a rationale for the development of an individual treatment plan for patients with locally advanced squamous cell carcinoma of the larynx, hypopharynx, and oropharynx by selecting different regimens of induction chemotherapy according to biological characteristics of the tumor and functional status of the patient.Materials and methods. We developed an individual treatment plan for a patient with stage IV moderately differentiated oropharyngeal squamous cell carcinoma (cT4N2M0) characterized by extensive local distribution, pronounced clinical symptoms of respiratory failure, and bilateral conglomerates of metastatic lymph nodes. The treatment scheme included paclitaxel (80 mg/m2), carboplatin AUC 2, and ce-tuximab (400 mg/m2 loading dose, then 250 mg/m2). The treatment was initially palliative. The patient received 6 injections once a week.Results. After a six-week course, we observed tumor resorption by more than 50 %, which allowed the second stage of treatment that included radical chemoradiotherapy with cetuximab. After summarizing our own experience, we found that the majority of patients with initially unresectable tumors, but in good overall physical condition responded to docetaxel, cisplatin, 5-fluorouracil (TPF) — based chemotherapy. Approximately half of them had complete tumor resorption, whereas 14.2 % of them had stabilization of the tumor process. Research literature shows that up to 30 % of patients receiving chemoradiotherapy with cisplatin fail to complete the planned treatment due to its toxicity; replacement of cisplatin with carboplatin and 5-fluorouracil results in mucositis and thrombocytopenia. By contrast, chemoradiotherapy with cetuximab significantly increases both 3-year and 5-year survival and demonstrates good tolerability. In patients with .severe nutritional deficiency, concomitant cardiac diseases, polyneuropathy, and impaired liver function, the preference should be given to less toxic treatment regimens.Conclusion. Cetuximab-containing chemotherapy regimens are the most effective treatment option in head and neck squamous cell carcinoma They can be used in patients with different functional status depending on the clinical situation

Possibilities of therapeutic use of HER2-inhibitorsin metastatic colorectal cancer: a case report

Current landscape of personalized and molecular-driven approach to cancer treatment contributes to a rapid growth of novel biomarkers used for a targeted therapy. Amplification or over-expression of HER2 has been shown to play an important role in the development and progression of some cancers. Recent studies have shown that over-expression of HER2 is found in up to 5% of colorectal cancers (CRC). These findings led to active research of therapeutic use of HER2-targeted therapy in a subset of patients with metastatic CRC, especially in patients with wild-type RAS, who progressed on anti-EGFR targeted therapy. According to data from several published studies, the rate of objective responses, progression-free and overall survival in this subset of patients matches or exceeds same rates that are achieved while using BRAF-targeted therapies in BRAF-mutated metastatic CRC patients and immunotherapy used in subjects diagnosed with MSI-H tumors. Currently, there is no conclusive data on potential of HER2-targeted therapy in RAS-mutated CRC patients. In this paper, we report a case of durable objective response obtained on trastuzumab therapy in patient with metastatic CRC, mutation in 12th exon of KRAS gene and over-expression of HER2 in 40% of tumor cells, after progression on several lines of chemotherapy and anti-angiogenic targeted therapy

Novel approaches to treatment of locally advanced rectal cancer

Combination of neoadjuvant chemoradiotherapy with subsequent total mesorectum excision and 6-months of adjuvant chemotherapy remains a standard approach to treatment of locally advanced rectal cancer (T3 or T4 and / or N1–3; M0) for more than 15 years, which is reflected in practical guidelines of most leading oncological societies. However, recent data suggests possibilities of more individualized treatment conceptions with a potential of further improvement of long-term therapy outcomes and patient’s quality of life. In this paper we present review of results of clinical trials which investigated new approaches to treatment of locally advanced rectal cancer

IMPACT OF THE COVID-19 PANDEMIC ON THE ONCOLOGICAL PRACTICE

Detailed, systematic review of the world literature data, including all aspects that reflect the impact of the COVID-19 pandemic on the oncological practice was conducted. The information sources were taken from Pubmed, MedLine, Scopus, Web of Science, and RSCI systems. The data from retrospective and prospective clinical trials have been analyzed. This review presents current data on the impact of COVID-19 on cancer patients, mortality and prognosis of cancer patients infected with COVID-19, treatment options for COVID-19, as well as the case report of the cancer patient with rare atypical COVID-19 course of disease. To date, the groups of increased risk of being infected with a new coronavirus have been identified. These groups include cancer patients. Despite the pandemic, treatment of cancer patients must be continued, since the presence of a tumor process does not allow the therapy to be delayed. The world cancer community is actively continuing to develop recommendations for optimal management of cancer patients in the context of the pandemic. The most relevant of them are described in this article

EFFICACY OF TARGET THERAPY WITH CRIZOTINIB IN A PATIENT WITH ALK-POSITIVE ADVANCED GASTRIC CANCER

Although many currently known molecular targets are characterized by organ specificity, they can be found in various types of tumors. Molecular diagnostic techniques can be used to help select patients who are most likely to benefit from target therapy. Case presentation. We describe the case of a 38-year-old patient with advanced gastric cancer with peritoneal dissemination. On december 11, 2014, the patient underwent palliative subtotal gastrectomy followed by 18 cycles of chemotherapy (xelOx) and radiotherapy. On February 2, 2017, percutaneous transhepatic cholangiostomy of the left lobe bile duct was performed. in May 2017, the stent was inserted into the common bile duct due to bile duct stenosis. three months later, disease progression (multiple liver metastases) occurred, and chemotherapy with paclitaxel was given in a weekly schedule. therapy with crizotinib was administered 3 months after determining the alK mutation. the duration of treatment was 8 months with satisfactory tolerability. Conclusion. target therapy with krizotinib seems to be an effective treatment for alK-positive tumors