A randomised phase II multicentre trial of irinotecan (CPT-11) using four different schedules in patients with metastatic colorectal cancer

The purpose of this phase II trial was to compare the efficacy, safety and pharmacokinetics of four irinotecan schedules for the treatment of metastatic colorectal cancer. In total, 174 5-fluorouracil pretreated patients were randomised to: arm A (n=41), 350 mg m(-2) irinotecan as a 90-min i.v. infusion q3 weeks; arm B (n=38), 125 mg m(-2) irinotecan as a 90-min i.v. infusion weekly x 4 weeks q6 weeks; arm C (n=46), 250 mg m(-2) irinotecan as a 90-min i.v. infusion q2 weeks; or arm D (n=49), 10 mg m(-2) day(-1) irinotecan as a 14-day continuous infusion q3 weeks. No significant differences in efficacy across the four arms were observed, although a shorter time to treatment failure was noted for arm D (1.7 months; P=0.02). Overall response rates were in the range 5-11%. Secondary end points included median survival (6.4-9.4 months), and time to progression (2.7-3.8 months) and treatment failure (1.7-3.2 months). Similarly, there were no significant differences in the incidence of grade 3-4 toxicities, although the toxicity profile between arms A, B, and C and D did differ. Generally, significantly less haematologic toxicity, alopecia and cholinergic syndrome were observed in arm D; however, there was a trend for increased gastrointestinal toxicity. Irinotecan is an effective and safe second-line treatment for colorectal cancer. The schedules examined yielded equivalent results, indicating that there is no advantage of the prolonged vs short infusion schedule

Long-term efficacy and safety of CT-P6 versus trastuzumab in patients with HER2-positive early breast cancer: final results from a randomized phase III trial

Purpose Equivalent efficacy was demonstrated for the biosimilar CT-P6 and trastuzumab following neoadjuvant therapy for patients with human epidermal growth factor receptor-2 (HER2)-positive early breast cancer. Following adjuvant treatment, efficacy and safety were comparable between treatments. We report updated safety and efficacy data after up to 3 years’ follow-up. Methods Following neoadjuvant chemotherapy with CT-P6/trastuzumab, patients underwent surgery and continued receiving adjuvant CT-P6/trastuzumab. The primary endpoint (previously reported) was pathological complete response. Time-to-event analyses (disease-free survival [DFS], progression-free survival [PFS], and overall survival [OS]), study drug-related and cardiac adverse events, and immunogenicity were assessed during post-treatment follow-up. Results Most patients entered the follow-up period (CT-P6: 259 [95.6%]; trastuzumab: 269 [96.8%]). After a median follow-up of 38.7 (CT-P6) and 39.6 (trastuzumab) months, medians were not reached for time-to-event parameters; estimated hazard ratios (HRs) and 3-year survival rates were similar between groups. Estimated HRs (95% confidence intervals) for CT-P6 versus trastuzumab were 1.23 (0.78–1.93) for DFS, 1.31 (0.86–2.01) for PFS, and 1.10 (0.57–2.13) for OS (intention-to-treat population). Safety findings were comparable between groups for the overall study and follow-up period, including study drug-related cardiac disorders (CT-P6: 22 [8.1%] patients; trastuzumab: 24 [8.6%] patients [overall]) and decreases in left ventricular ejection fraction. Immunogenicity was similar between groups. Conclusion The similarity of the time-to-event analyses between CT-P6 and trastuzumab supports the equivalence in terms of efficacy established for the primary endpoint. CT-P6 was well tolerated, with comparable safety and immunogenicity to trastuzumab. ClinicalTrials.gov: NCT02162667 (registered June 13, 2014

Comprehensive Screening for COVID-19 at St. Petersburg Oncology Centre

Background. Clinical reports on the coronavirus disease 2019 (COVID-19) suggest its higher incidence and worse outcomes in cancer patients. Considering a rapid pace of the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) pandemic, more data on the risk of contagion and syndrome course is required with this patient group.Aim. Estimation of the infection rate in cancer patients managed at the Oncology Centre.Materials and methods. This retrospective study included cancer patients managed at the Oncology Centre between 9 April 2020 and 27 May 2020 and routinely tested for SARS-CoV-2 in polymerase chain reaction (PCR) assays and/or COVID-19 in chest computed tomography (CT).Results and discussion. A total of 2,628 patients were included in the study, with 119 (4.5 %) confirmed to have COVID-19; 45/119 were PCR-positive, 95/119 had viral pneumonia in CT, 21/119 were positive for both tests. A total of 47.9 % cases were asymptomatic, 11.8 % revealed a mild single-symptom disease. COVID-19 ended in death in 2 (2.5 %) of 80 cases with a known outcome. In PCR results of both patient and staff screening, the virus detection rate was 3.0 % and 2.4 %, respectively (p = 0.33).Conclusion. A COVID-19 screening revealed no significant difference in the risk of contagion between cancer patients and staff of the Oncology Centre. PCR tests may perform false negative for COVID-19 in cancer patients and should be coupled with CT scanning. The infection is asymptomatic or clinically mild in most other cases

Phase II study of docetaxel and irinotecan combination chemotherapy in metastatic gastric carcinoma

The current treatment for metastatic gastric cancer (MGC) consists of cisplatin and/or fluorouracil (5-FU) based combination chemotherapy, but cisplatin-based regimens are associated with considerable toxicity. We evaluated the efficacy and safety of a noncisplatin-, non-5-FU-containing regimen, docetaxel/irinotecan in MGC. Chemo-naive patients with MGC received docetaxel (30 mg m−2) and irinotecan (70 mg m−2) on days 1 and 8 every 3 weeks. The 48 eligible patients (median age 56 years) received a median of four cycles of docetaxel/irinotecan (range 1–18). Of the 46 patients in whom efficacy could be evaluated, 21 showed a partial response (response rate=45.7%; 95% confidence interval (CI) 31.3–60.1%). At a median follow-up of 15.0 months, the median time to progression was 4.5 months (95% CI 3.8–5.2 months) and overall survival was 8.2 months (95% CI, 5.8–10.6 months). Grade 3/4 neutropenia developed in 57.4% of patients, and febrile neutropenia/neutropenic infection in 19.1%. Nonhaematological toxicities were moderate; grade 3/4 diarrhoea occurred in 19.1% of patients, however, was manageable by a dose reduction. There was one possible treatment-related death. In conclusion, weekly docetaxel/irinotecan is a promising outpatient regimen in MGC, with appropriate dose modification

Результаты применения иммунотерапевтических препаратов при немелкоклеточном раке легкого в реальной клинической практике

The evolution of drug therapy in solid tumors primarily leads to the increase in cancer specific survival, but inevitably raises financial burden. So far, none of the countries can venture total reimbursement with all necessary contemporary drugs for all patients. Doubling of expenses for cancer drug therapy in Russia in 2019 allowed oncologists using the most expensive treatments in more than 70 % of patients.Purpose: To evaluate efficacy of various treatment types of non‑small cell lung cancer in real clinical setting.Material and methods. We included patients with histologically verified metastatic non‑small cell lung cancer without activating mutations treated with first or second line therapy in 2018 – 2019. In total 287 patients were included: 230 — for the first line efficacy analysis, 100 — for the second. Time to disease progression, overall survival and objective response rate were evaluated.Results. The use of checkpoint inhibitors in accordance with all actual recommendations (first line pembrolizumab monotherapy in PD-L1 > 50 %, chemoimmunotherapy in first line or monotherapy in the second line irrespectively to PD-L1 status) decreased one‑year mortality from 61 % in 2018 to 33 % in 2019, but significantly increased financial cost (p < 0.000). Moreover, checkpoint inhibitors in combination with chemotherapy irrespectively of PD-L1 expression increased response rate (from 10 % and 21 % for monotherapy and platinum doublet, respectively, to 33,2 % for chemoimmunotherapy). PD‑1 inhibitors as monotherapy increased median time to disease progression (4,1 and 6,2 months for monotherapy with chemotherapy and platinum doublet, respectively, to 6,5 months and not achieved for chemoimmunotherapy and monotherapy with checkpoint inhibitors).Conclusion. More than doubling of financial costs spent for non‑small cell lung cancer treatment allowed access to contemporary treatment for all patients. Such unprecedented measures significantly improved efficacy, including double decrease of one‑year mortality. Nevertheless, rational design of regional clinical guidelines interpretation is of great importance in accurate and effective use of the healthcare budget.Совершенствование лекарственной терапии злокачественных опухолей позволяет существенно увеличить продолжительность жизни пациентов, но неминуемо ведет на ранних этапах внедрения к повышению затрат на лекарственное обеспечение. Ни одна из стран мира на настоящий момент не может позволить себе полное обеспечение новейшими лекарственными препаратами всех больных. Двукратное увеличение расходов на лекарственное лечение на территории РФ в течение 2019 года позволило обеспечить современными препаратами 70 % нуждавшихся пациентов немелколеточным раком легкого (НМРЛ).Цель. Оценить клиническую эффективность различных методов лекарственной терапии рака легкого в реальной клинической практике.Материалы и методы. В анализ включались пациенты с гистологически верифицированным неоперабельным НМРЛ, получавшие первую или вторую линию терапии в 2018–2019 гг. В исследование были включены 287 пациентов с НМРЛ: 230 больных для оценки эффективности первой линии, 100 — второй. Были оценены: время без прогрессирования, общая выживаемость, частота объективных ответов.Результаты. Применение ингибиторов контрольных точек в любом из зарегистрированных вариантов (первая линия при PD-L1 > 1 %, химиоиммунотерапия независимо от статуса PD-L1, вторая линия независимо от статуса PD-L1) позволяет снизить одногодичную летальность с 61 % до 33 %, однако приводит к достоверному увеличению затрат на лекарственное обеспечение (р< 0,000). Кроме того, использование ингибиторов контрольных точек в монорежиме у больных с высоким уровнем экспрессии PD-L1 или в комбинации с цитостатическими препаратами позволяло увеличить частоту объективных ответов (10 % и 21 % для монотерапии и платиновых дуплетов против 33,2 % для химиоиммунотерапии), медиану времени без прогрессирования (4,1 и 6,2 месяца для монотерапии и платиновых дуплетов против 6,5 месяцев для химиоиммунотерапии, тогда как медиана для монотерапии ингибиторами контрольных точек не достигнута).Выводы. Более чем 2-кратное повышение финансирования лекарственного лечения позволило обеспечить современными препаратами всех нуждавшихся пациентов НМРЛ. Подобные меры позволили достоверно увеличить продолжительность жизни больных НМРЛ. Тем не менее, рациональное использование подобных ресурсов требует выработки жестких критериев для того или иного дорогостоящего метода лечения

Оценка токсичности и эффективности терапии комбинацией FOLFIRI и афлиберцепта при метастатическом раке толстой кишки в РФ: первые результаты многоцентрового ретроспективного исследования

oai:oai.tumors.elpub.ru:article/629Purpose. To assess the incidence and severity of adverse events; to explore clinical factors associated with grade 3–4 non-hematologic toxicity; to assess the immediate efficacy and progression-free survival during treatment with the FOLFIRI regimen in combination with aflibercept in Russia.Materials and Methods. A retrospective multicenter study has been conducted with data collected from 20 clinics in 15 regions of Russia. There was no statistical hypothesis. Progression-free survival was the main efficacy criterion. The statistical analysis was performed using IBM SPPS Statistics v. 20 software.Results. FOLFIRI and Aflibercept combination was administered to 264 patients. The mean number of treatment cycles was 6 (1 to 29). The toxicity of aflibercept was addressed by dose reduction and dosing delay in 10.1 % and 11.4 % of patients, respectively, and dose reductions and dosing delays in any of FOLIFRI components were reported in 20.1 % of participants. The objective response rate was 20.3 %. The median progression-free survival in patients receiving second-line treatment was 6 months (95 % CI: 5.3–6.6 months). Seventy-two percent of patients experienced any grade of adverse events most of which were limited to grade 1–2 (62.1 %). Non-hematologic toxicity was reported in 64 % of patients (grade 3–4 in 17.9 %). Hematologic events were detected in only 17.9 % of patients. Multifactorial analysis has shown that drug therapy for concomitant diseases (OR 1.98, 95 % CI: 1.04–3.78, p = 0.037) and the number of chemotherapy lines prior to aflibercept (ОR 1.5, 95 % CI: 1.06–2.11, p = 0.02) were independent predictors of grade 3–4 non-hematologic toxicity.Conclusions. Objective response rate, progression-free survival, and frequency of toxicity-related aflibercept discontinuations in the Russian study with patients receiving aflibercept in combination with FOLFIRI regimen as a second-line treatment has shown the results that were comparable with VELOUR study. Comorbidities requiring drug treatment and the number of prior chemotherapy lines appear to be risk factors for grade 3–4 nonhematological toxicity events. Цель исследования. Оценить частоту развития и тяжесть нежелательных явлений; изучить клинические факторы, ассоциированные с развитием негематологической токсичности 3-4 степени; оценить непосредственную эффективность выживаемость без прогрессирования при применении комбинации FOLFIRI с афлиберцептом в РФ.Материалы и методы. Проведено ретроспективное многоцентровое исследование. Собраны данные 20 клиник 15 регионов РФ. Статистическая гипотеза отсутствовала. В качестве основного критерия эффективности рассматривалась выживаемость без прогрессирования. Статистический анализ проводился с помощью программ статистического пакета SPSS (IBM SPPS Statistics v. 20).Результаты. Режим FOLFIRI афлиберцепт был назначен у 264 пациентов. Среднее число составило 6 (от 1 до 29). В связи с токсичностью доза афлиберцепта в процессе терапии была редуцирована у 10,1% пациентов, задержали очередное введение афлиберцепта — у 11,4%; отсрочка и редукция доз химиопрепаратов в режиме FOLFIRI описана у 20,1 %. Частота объективных эффектов составила 20,3%. Во второй линии терапии медиана выживаемости без прогрессирования составила 6 месяцев (95% ДИ 5,3-6,6 месяцев). Нежелательные явления любой степени зарегистрированы у 72 % пациентов и чаще были ограничены 1-2 степенью (62,1%). Негематологические осложнения развились у 64% (3-4 степень — у 17,9%). Гематологические осложнения представлены только у 17,9 % пациентов. По результатам многофакторного анализа лекарственная терапия по поводу сопутствующей патологии (ОШ 1,98, 95%ДИ 1,04-3,78, р=0,037) и число линий терапии (ОШ 1,5, 95%ДИ 1,06-2,11, р=0,02), предшествующих афлиберцепту, явились независимыми предсказывающими факторами развития нежелательных явлений негематологического профиля 3-4 степени.Выводы. Частота объективных эффектов, выживаемость без прогрессирования и частота отмены афлиберцепта в связи с токсическими реакциями при применении комбинации FOLFIRI + афлиберцепт во второй линии среди пациентов в РФ аналогична результатам исследования VELOUR. Сопутствующая патология, требующая медикаментозной коррекции, и число линий терапии предшествующих афлиберцепту, по-видимому, являются факторами риска развития негематологических явлений 3-4 степени