Selinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial

PURPOSE Antitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents. METHODS SEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study. Patients age 12 years or older with advanced DD-LPS who had received two-five lines of therapy were randomly assigned (2:1) to selinexor (60 mg) or placebo twice weekly in 6-week cycles (crossover permitted). The primary end point was progression-free survival (PFS). Patients who received at least one dose of study treatment were included for safety analysis (ClinicalTrials.gov identifier: ). RESULTS Two hundred eighty-five patients were enrolled (selinexor, n = 188; placebo, n = 97). PFS was significantly longer with selinexor versus placebo: hazard ratio (HR) 0.70 (95% CI, 0.52 to 0.95; one-sided P = .011; medians 2.8 v 2.1 months), as was time to next treatment: HR 0.50 (95% CI, 0.37 to 0.66; one-sided P < .0001; medians 5.8 v 3.2 months). With crossover, no difference was observed in overall survival. The most common treatment-emergent adverse events of any grade versus grade 3 or 4 with selinexor were nausea (151 [80.7%] v 11 [5.9]), decreased appetite (113 [60.4%] v 14 [7.5%]), and fatigue (96 [51.3%] v 12 [6.4%]). Four (2.1%) and three (3.1%) patients died in the selinexor and placebo arms, respectively. Exploratory RNA sequencing analysis identified that the absence of CALB1 expression was associated with longer PFS with selinexor compared with placebo (median 6.9 v 2.2 months; HR, 0.19; P = .001). CONCLUSION Patients with advanced, refractory DD-LPS showed improved PFS and time to next treatment with selinexor compared with placebo. Supportive care and dose reductions mitigated side effects of selinexor. Prospective validation of CALB1 expression as a predictive biomarker for selinexor in DD-LPS is warranted. (C) 2022 by American Society of Clinical Oncolog

Building the Evidence for Systemic Treatment in Desmoid Fibromatosis: Is a New Metronomic Regimen Another Layer in the Foundation?

@Thalcin explains how a metronomic regimen for desmoid tumors fits in the current treatment landscape

Secondary Polycythemia in a Sarcoma Patient: A Commentary about Cediranib

Cediranib, a potent inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, platelet-derived growth factor subunit B, and the c-Kit receptor tyrosine kinase, has shown antitumour activity as an antiangiogenic agent in preclinical models. Initial clinical trials with cediranib in a variety of tumour types, including glioblastoma multiforme, non-small-cell lung cancer, renal cell cancer, colorectal cancer, and prostate cancer, showed activity comparable to that for other vascular endothelial growth factor (vegf) inhibitors, but with significant toxicities, resulting in abandonment of the drug’s development in 2011. [...

Gemcitabine-Containing Chemotherapy for the Treatment of Metastatic Myxofibrosarcoma Refractory to Doxorubicin: A Case Series

Background: Myxofibrosarcoma is a type of soft-tissue sarcoma that is associated with high rates of local recurrence and distant metastases. The first-line treatment for metastatic soft-tissue sarcoma has conventionally been doxorubicin-based. Recent evidence suggests that myxofibrosarcoma may be molecularly similar to undifferentiated pleomorphic sarcoma (UPS), which is particularly sensitive to gemcitabine-based therapy. The goal of this study was to evaluate the activity of gemcitabine-containing regimens for the treatment of metastatic myxofibrosarcoma refractory to doxorubicin. Material and Methods: We retrospectively evaluated seven consecutive cases of metastatic myxofibrosarcoma at our institution treated with gemcitabine-based therapy in the second-line setting, after progression on doxorubicin. Baseline clinical and baseline characteristics were collected. Primary endpoints were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: After progression on first-line doxorubicin, a partial, or complete radiological response was observed in four of seven patients who received gemcitabine-based chemotherapy. With a median follow-up of 14 months, median progression-free and overall survival were 8.5 months and 11.4 months, respectively. Conclusions: Gemcitabine-based chemotherapy was associated with encouraging response rates in this cohort, similar to those seen in UPS. Both entities could be studied together for novel gemcitabine-based regimens

Clinical Benefit from Lenvatinib and Pembrolizumab Observed in Mullerian Adenosarcoma: A Case Report

A 32-year-old woman with chemorefractory mullerian adenosarcoma showed clinical benefit in response to administration of lenvatinib plus pembrolizumab. In this case report, we describe the course of her illness and her response to this treatment

Psychological functioning, coping styles and their relationship to appraisal of physical limitations following invasive surgical procedures for soft‐tissue sarcoma: A qualitative study

Background and Objectives This study explored psychological functioning and coping styles in adult patients with soft‐tissue sarcoma who underwent surgical procedures in a single expert sarcoma medical center in Canada. Methods This is a qualitative study with three formats of data collection. The interview guide was based on theoretical health‐related quality of life model. We began the investigation with 2 online and 2 in‐person focus groups. Four individual semistructured interviews were added to further explore emerging themes. Data were analyzed using inductive thematic networks approach. Results Twenty‐eight adults (13 female, 24‐75 years of age) participated. In the domain of psychological functioning we identified three main themes; changes in mood, worry, and body image concerns. In the domain of coping styles, we identified four adaptive coping styles; positive reframing and optimism, finding a purpose, being proactive, and using humor. Among the maladaptive coping styles, we found passive acceptance, and avoidance and denial. Conclusions Psychological well‐being can be contingent on physical functioning and coping styles in adults with soft‐tissue sarcoma. Both psychological and physical function impact quality of life. Patients with more physical limitations, psychological distress and maladaptive coping styles should be monitored for their well‐being