Elenagen is a plasmid encoding p62/SQSTM1, the first DNA vaccine possessing two mutually complementing mechanisms of action: it elicits immune response against p62 and mitigates systemic chronic inflammation. Previously, Elenagen demonstrated anti-tumor efficacy and safety in rodent tumor models and spontaneous tumors in dogs. This multicenter I/IIa trial evaluated safety and clinical activity of Elenagen in patients with advanced solid tumors. Fifteen patients were treated with escalating doses of Elenagen (1- 5 mg per doses, 5 times weekly) and additional 12 patients received 1 mg dose. Ten patients with breast and ovary cancers that progressed after Elenagen were then treated with conventional chemotherapy. Adverse events (AE) were of Grade 1; no severe AE were observed. Cumulatively twelve patients (44%) with breast, ovary, lung, renal cancer and melanoma achieved stable disease for at least 8 wks, with 4 of them (15%) had tumor control for more than 24 wks, with a maximum of 32 wks. The patients with breast and ovary cancers achieved additional tumor stabilization for 12-28 wks when treated with chemotherapy following Elenagen treatment. Therefore, Elenagen demonstrated good safety profile and antitumor activity in advanced solid tumors. Especially encouraging is its ability to restore tumor sensitivity to chemotherapy.
Triple-negative breast cancers are often characterized by aggressive behavior and short clinical course once they become chemotherapy-resistant. We describe below a patient who has shown a response to combination of chemotherapy with Elenagen, a plasmid encoding p62. Elenagen was tested in a previous phase I/II study in patients with refractory solid tumors and shown to be safe. Also, plasmid ability to halt tumor progression and restore sensitivity to chemotherapy was found. Preclinical data supports effects on tumor grade and change the tumor's microenvironment in spontaneous canine breast cancers. We describe here a 48-year old female with triple-negative and BRCA1/2-negative breast cancer who had a primary resistance to chemotherapy and negative dynamics despite the use of multiple lines of treatments. Elenagen was applied intramuscularly at a dose of 1 mg weekly in combination with standard chemotherapy scheme CMF (cyclophosphamide, methotrexate, fluorouracil). In this patient we observed partial tumor regression (by 33%) and 19 weeks of progression-free survival. This first observed objective response to a combination of Elenagen with chemotherapy demonstrates that even in heavily pretreated chemoresistant triple-negative tumor, the addition of Elenagen to a chemotherapy regimen can cause an objective response and increase in progression-free survival. Such a regimen is worthy of further study in a larger number of patients.
This study contributes to a better understanding of prognostic and predictive factors of NSCLC in the Russian Federation, which will enable optimal treatment selection in future clinical practice. Epidemiology of EGFR mutations in this NSCLC cohort was similar to other studies of NSCLC in Caucasian populations.
e12580 Background: Eribulin demonstrates improved overall survival compared to standard treatments, Her2-negative and TNBC patients have the most survival benefit. We sought to describe treatment patterns of eribulin and clinical outcomes among TNBC patients with advanced breast cancer treated in community oncology practices across the Russian Federation. Methods: Patients treated with eribulin anytime between January 1, 2014 and January 1, 2017 with a diagnosis of MBC were identified by providers within the Russia Oncology Research Center. Providers reviewed the health records (electronic or paper-based) and abstracted selected data points into an electronic case report form for each eligible patient. Results: A total 52 TNBC patients were considered by 10 providers. A median of age at start of eribulin was 47,5 (39-55) yrs and ECOG status 0-1 were assessed. Most of the pts (92,3%) had visceral mts, a median number metastatic disease regions was 2 (1-3). Eribulin was administered as the 1st and 2nd line of BC treatment to 14 (26,9%) pts, 3rd line – to 9 (17,3%), the 4thand later lines – to 29 (55,8%) pts. Objective response occurred in 5 (9,6%) pts. Stable disease registered in 24 (46,1%) pts. Median PFS was 3,0 months (95% CI 1,9-8,55). Overall the drug was well tolerated. The most common type of toxicity was hematologic. Neutropenia gr II was observed in 8 (15,4) pts and III-IV gr in 6 (11,5%), two cases of febrile neutropenia were registered. 4 (7,7%) pts experienced fatigue gr II. Peripheral neuropathy gr II was observed in 4 (7,7%) pts. Dose reduction due to toxicity was performed in 8 (15,4%) pts. Treatment was never withdrawn due to toxicity. Conclusions: This is the first real-life study of clinical outcomes, for patients initiating eribulin therapy for TNBC in community oncology practices throughout the Russian Federation. . Our experience with Eribulin in TNBC patients confirms it efficacy and safety in all lines of treatment, including intensively pretreated patients in this hard-to-treat population.
e13111 Background: First large Russian ovarian cancer observational study was conducted in 2014-2018. Methods: A total of 500 patients in 29 sites in Russia with newly diagnosed ovarian, peritoneal and fallopian tube cancer was enrolled (NCT02122588). The primary objective was to describe treatment approaches in the first line treatment. 141 patients (pts) with BRCA1/2 mutations (BRCA1/2mt) detected by NGS in blood and tissue were observed prospectively during at least 2 years. Results: Rate of BRCA1/2 mutations in Russian population is high – 28.4% (141 from 496 available for any testing). 77.6% (388/500) underwent biomarkers blood testing prior to treatment. CA-125 was positive in 99.7% (387/388), 15.2% (59/388) of pts had positive CA19-9, CA72-4 - in 2.3% (9/388). Positive CEA was presented in 15.2% (59/388). This marker was detected more frequently in BRCA2mt pts subgroup (28.0% (7/25)) than in BRCA1mt pts: 9.0% (8/90) (p = 0.05). 26.6% (133/500) of all study population had an oncology family history; 44.0% (62/141) BRCA1/2mt pts had relatives with oncological diseases and 19.7% (70/355) in BRCA wild type pts (p = 0.0001). 98.6% (139/141) of BRCA1/2mt pts received first line therapy. Objective response rate was registered in 79.8% (111/139) pts. Progression after platinum based regimens was observed in 53.6% (59/110) BRCA1mt pts and 44.8% (13/29) BRCA2mt pts. 35.6 % (21/59) of BRCA1mt pts had platinum-refractory and platinum-resistant relapses, while 15.4% in BRCA2mt subgroup (2/13) (p = 0.64). Platinum-sensitive relapses were in 64.4% (38/59) BRCA1mt pts and 84.6% BRCA2mt (11/13) (p = 0,64). Median PFS in BRCA1/2mt pts was 25.5 months. Among BRCA1/2mt pts underwent cytoreduction median PFS in subgroup without visible residual tumor was 36.4 months and in subgroup with residual tumor < 1 cm 15.3 months. Conclusions: In this large-scale prospective non-interventional study diagnostics and treatment approaches in Russian ovarian cancer pts were evaluated and high frequency of BRCA1/2mt was observed. Pts with BRCA1/2mt had better prognosis and most of them had platinum-sensitive relapses after first line chemotherapy that allowed platinum-based regimen rechallenge.
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