Tumor Treating Fields (TTFields) Therapy Concomitant with Taxanes for Cancer Treatment

Non-small cell lung cancer; Ovarian cancer; Pancreatic cancerCáncer de pulmón de células no pequeñas; Cáncer de ovarios; Cáncer de páncreasCàncer de pulmó de cèl·lules no petites; Càncer d'ovaris; Càncer de pàncreesNon-small cell lung cancer, ovarian cancer, and pancreatic cancer all present with high morbidity and mortality. Systemic chemotherapies have historically been the cornerstone of standard of care (SOC) regimens for many cancers, but are associated with systemic toxicity. Multimodal treatment combinations can help improve patient outcomes; however, implementation is limited by additive toxicities and potential drug–drug interactions. As such, there is a high unmet need to develop additional therapies to enhance the efficacy of SOC treatments without increasing toxicity. Tumor Treating Fields (TTFields) are electric fields that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. The therapy is locoregional and is delivered noninvasively to the tumor site via a portable medical device that consists of field generator and arrays that are placed on the patient’s skin. As a noninvasive treatment modality, TTFields therapy-related adverse events mainly consist of localized skin reactions, which are manageable with effective acute and prophylactic treatments. TTFields selectively target cancer cells through a multi-mechanistic approach without affecting healthy cells and tissues. Therefore, the application of TTFields therapy concomitant with other cancer treatments may lead to enhanced efficacy, with low risk of further systemic toxicity. In this review, we explore TTFields therapy concomitant with taxanes in both preclinical and clinical settings. The summarized data suggest that TTFields therapy concomitant with taxanes may be beneficial in the treatment of certain cancers.All costs related to publication were funded by Novocure Inc

Revisiting Reader Privacy in the Age of the E-Book, 45 J. Marshall L. Rev. 175 (2011)

status: publishe

Investigational drugs for recurrent or primary advanced metastatic cervical cancer: what is in the clinical development pipeline?

Recurrent cervical cancer; Combination therapy; ImmunotherapyCáncer cervical recurrente; Terapia de combinación; InmunoterapiaCàncer cervical recurrent; Teràpia combinada; ImmunoteràpiaIntroduction: Recurrent or primary advanced metastatic cervical cancer (R/M CC) has a poor prognosis with a 5-year-survival rate of 16.5%, demanding novel and improved therapies for the treatment of these patients. The first-line standard of care for R/M CC now benefits from the addition of the immune checkpoint inhibitor, pembrolizumab, to platinum-based chemotherapy with paclitaxel and bevacizumab. Additionally, new options for second-line treatment have become available in recent years. Areas covered: Here, we review current investigational drugs and discuss their relative targets, efficacies, and potential within the R/M CC treatment landscape. This review will focus on recently published data and key ongoing clinical trials in patients with R/M CC, covering multiple modes of action, including immunotherapies, antibody-drug conjugates, and tyrosine kinase inhibitors. We searched clinicaltrials.gov for ongoing trials and pubmed.ncbi.nih.gov for recently published trial data, as well as recent years' proceedings from the annual conferences of the American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), European Society of Gynaecological Oncology (ESGO), and the International Gynecologic Cancer Society (IGCS). Expert opinion: Therapeutics currently attracting attention include novel immune checkpoint inhibitors, therapeutic vaccinations, antibody-drug conjugates, such as tisotumab vedotin, tyrosine kinase inhibitors targeting HER2, and multitarget synergistic combinations

Safety and activity of anti-mesothelin antibody–drug conjugate anetumab ravtansine in combination with pegylated-liposomal doxorubicin in platinum-resistant ovarian cancer: multicenter, phase Ib dose escalation and expansion study

Ovarian cancerCàncer d'ovariCáncer de ovarioObjectives Anetumab ravtansine is an antibody-drug conjugate consisting of a fully human anti-mesothelin monoclonal antibody conjugated to cytotoxic maytansinoid tubulin inhibitor DM4. Mesothelin is highly expressed in ovarian cancer. This phase Ib study determines the safety, pharmacokinetics, and anti-tumor activity of anetumab ravtansine and pegylated liposomal doxorubicin in mesothelin-expressing platinum-resistant ovarian cancer. Methods Anetumab ravtansine (5.5 or 6.5 mg/kg) and pegylated liposomal doxorubicin (30 mg/m2) were administered intravenously every 3 weeks to 65 patients with platinum-resistant epithelial ovarian cancer. Mesothelin expression was assessed by central immunohistochemistry. Adverse events, tumor response (RECIST 1.1), and progression-free survival were determined. Biomarker samples were assessed by ELISA and next-generation sequencing. Results In dose escalation, nine patients received anetumab ravtansine across two doses (5.5 or 6.5 mg/kg). The maximum tolerated dose of anetumab ravtansine was 6.5 mg/kg every 3 weeks and no dose-limiting toxicities were observed. In dose expansion, 56 patients were treated at the maximum tolerated dose. The most common treatment-emergent adverse events of any grade were nausea (47.7%), decreased appetite (43.1%), fatigue (38.5%), diarrhea (32.3%), and corneal disorder (29.2%). In all treated patients the objective response rate was 27.7% (95% CI 17.3% to 40.2%), including one complete (1.5%) and 17 partial responses (26.2%), with median duration of response of 7.6 (95% CI 3.3 to 10.2) months and median progression-free survival of 5.0 (95% CI 3.2 to 6.0) months. In an exploratory analysis of a sub-set of patients (n=19) with high mesothelin expression who received ≤3 prior lines of systemic therapy, the objective response rate was 42.1% (95% CI 20.3% to 66.5%) with a median duration of response of 8.3 (95% CI 4.1 to 12.0) months and median progression-free survival of 8.5 (95% CI 4.0 to 11.4) months. Conclusions Anetumab ravtansine and pegylated liposomal doxorubicin showed tolerability and promising clinical activity. These results established the dose schedule and the mesothelin-positive target population of this combination for a phase III study in platinum-resistant ovarian cancer.This study was funded by Bayer AG

EMPOWER CERVICAL-1: Effects of cemiplimab versus chemotherapy on patient-reported quality of life, functioning and symptoms among women with recurrent cervical cancer

Chemotherapy; Quality of life; SymptomsQuimioterapia; Calidad de vida; SíntomasQuimioteràpia; Qualitat de vida; SímptomesBackground In a phase III, randomised, active-controlled study (EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9; R2810-ONC-1676; NCT03257267) and cemiplimab significantly improved survival versus investigator's choice of chemotherapy among patients with recurrent cervical cancer who had progressed on platinum-based therapy. Here we report patient-reported outcomes in this pivotal study. Methods Patients were randomised 1:1 to open-label cemiplimab (350 mg intravenously every 3 weeks) or investigator's choice of chemotherapy in 6-week cycles. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 during cycles 1–16. Least-squares mean changes from baseline in global health status (GHS)/quality of life (QoL) and physical functioning (PF) were secondary end-points in the statistical hierarchy. Results Of 608 patients (304/arm), 77.8% patients had squamous cell carcinoma and 22.2% patients had adenocarcinoma. Questionnaire completion rates were ∼90% throughout. In the squamous cell carcinoma population, overall between-group differences statistically significantly favoured cemiplimab in GHS/QoL (8.49; 95% confidence interval [CI]: 3.77–13.21; P = 0.0003) and PF (8.35; 95% CI: 4.08–12.62; P < 0.0001). Treatment differences favoured cemiplimab in both histologic populations by cycle 2. Overall changes from baseline in most functioning and symptom scales favoured cemiplimab, with clinically meaningful treatment differences in role functioning, appetite loss and pain in both populations. The sensitivity analyses, responder analyses and time to definitive deterioration favoured cemiplimab in both populations. Conclusions Cemiplimab conferred favourable differences in GHS/QoL and PF compared with chemotherapy among patients with recurrent cervical cancer, with benefits in PF by cycle 2, and clinically meaningful differences favouring cemiplimab in role functioning, appetite loss, and pain.This work was supported by Regeneron Pharmaceuticals, Inc., and Sanofi

A phase II multicentre, open-label, proof-of-concept study of tasquinimod in hepatocellular, ovarian, renal cell, and gastric cancers

Background: Tasquinimod is a small molecule with immunomodulatory, anti-angiogenic, and anti-metastatic properties that targets the tumor microenvironment. This study aimed to obtain a clinical proof of concept that tasquinimod was active and tolerable in patients with advanced solid tumors. Patients and Methods: This early stopping design, open-label, proof-of-concept clinical trial evaluated the clinical activity of tasquinimod in four independent cohorts of patients with advanced hepatocellular (n = 53), ovarian (n = 55), renal cell (n = 38), and gastric (n = 21) cancers. Tasquinimod was given orally every day (0.5 mg/day for at least 2 weeks, with dose increase to 1 mg/day) until radiological progression according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 criteria, intolerable toxicity, or patient withdrawal. The primary efficacy endpoint was progression-free survival (PFS) rate according to RECIST 1.1 by central assessment. Results: Interim futility analyses at 8 weeks (6 weeks for the gastric cancer cohort) found adequate clinical activity of tasquinimod only in the hepatocellular cohort and recruitment to the other three cohorts was stopped. PFS rates were 26.9% at 16 weeks, 7.3% at 24 weeks, 13.2% at 16 weeks, and 9.5% at 12 weeks, respectively, in hepatocellular, ovarian, renal cell, and gastric cancer cohorts. The pre-defined PFS threshold was not reached in the hepatocellular cancer cohort at the second stage of the trial. The most common treatment-related adverse events were fatigue (48.5%), nausea (34.1%), decreased appetite (31.7%), and vomiting (24.6%). Conclusions: This study failed to demonstrate clinical activity of tasquinimod in heavily pre-treated patients with advanced hepatocellular, ovarian, renal cell, and gastric cancer. Trial registration: NCT01743469

High-grade endometrial stromal sarcoma presenting in a 28-year-old woman during pregnancy: a case report

<p>Abstract</p> <p>Introduction</p> <p>To the best of our knowledge, soft tissue sarcomas have not prevously been reported as a complication during pregnancy.</p> <p>Case presentation</p> <p>A 28-year-old Caucasian woman was diagnosed with a transperitoneal sarcoma during pregnancy. Morphological, immunohistochemical, chromosomal and mutational analyses pointed towards a high-grade endometrial stromal sarcoma. Although surgery and chemotherapy are possible during pregnancy, we were unable to perform these in this case.</p> <p>Conclusion</p> <p>The potential to treat gynecological cancer during pregnancy should always be assessed individually.</p

FORWARD I: a Phase III study of mirvetuximab soravtansine versus chemotherapy in platinum-resistant ovarian cancer

Mirvetuximab soravtansine, an antibody-drug conjugate that binds with high affinity to folate receptor-alpha to provide tumor-directed delivery of the potent microtubule-disrupting agent DM4, has emerged as a promising investigational agent for the treatment of ovarian cancer, particularly in the setting of platinum-resistant disease. Here we describe the rationale and design of FORWARD I (NCT02631876), the first randomized, multicenter Phase III study to compare the safety and efficacy of mirvetuximab soravtansine versus investigator's choice of chemotherapy in women with folate receptor-alpha-positive, platinum-resistant epithelial ovarian, primary peritoneal or fallopian tube cancer. Patients will be randomized in a 2:1 ratio. The primary end point is progression-free survival, and key secondary objectives include comparison of overall response rates, overall survival and duration of response

Taxpayer Compliance, Trust, and Power

Self-assessment system as adopted in Indonesia, focusing on taxpayer awareness. Therefore trust should be the spearhead of tax compliance rather than power. This study aims to examine how trust and power play a role in improving tax compliance by the slippery slope framework. Method of data collection in this research surveys in Central Java. The sampling technique is a multi-stage sampling that combines stratified random sampling and convenience sampling. Data has been collected from October 2015-April 2016, and 242 instruments were collected (86.4 percent response rate). By using multiple regression tests, the results of this study indicate that trust and power both simultaneously and partially affect tax compliance. Based on the coefficient different test, power has a greater impact than trust in creating tax compliance. This means that the compliance created in Indonesia is mandatory compliance that denies from self-assessment system that based on voluntary compliance.JEL Classification: H26; G41DOI: https://doi.org/10.26905/jkdp.v22i2.158

European Network of Gynaecological Oncological Trial Groups’ requirements for trials between academic groups and industry partners – a new Model D for drug and medical device development

No abstract available