BackgroundEwing sarcoma (EWS) is an aggressive sarcoma with few treatment options for patients with relapsed disease. Cyclin‐dependent kinase 4 (CDK4) is a genomic vulnerability in EWS that is synergistic with IGF‐1R inhibition in preclinical studies. We present the results of a phase 2 study combining palbociclib (CDK4/6 inhibitor) with ganitumab (IGF‐1R monoclonal antibody) for patients with relapsed EWS.Patients and MethodsThis open‐label, non‐randomized, phase 2 trial enrolled patients ≥12 years with relapsed EWS. All patients had molecular confirmation of EWS and RECIST measurable disease. Patients initially received palbociclib 125 mg orally on Days 1–21 and ganitumab 18 mg/kg intravenously on Days 1 and 15 of a 28‐day cycle. The primary endpoints were objective response (complete or partial) per RECIST and toxicity by CTCAE. An exact one‐stage design required ≥4 responders out of 15 to evaluate an alternative hypothesis of 40% response rate against a null of 10%. The study was closed following enrollment of the 10th patient due to discontinuation of ganitumab supply.ResultsTen evaluable patients enrolled [median age 25.7 years (range 12.3–40.1)]. The median duration of therapy was 2.5 months (range 0.9–10.8). There were no complete or partial responders. Three of 10 patients had stable disease for >4 cycles and 2 had stable disease at completion of planned therapy or study closure. Six‐month progression‐free survival was 30% (95% CI 1.6%–58.4%). Two patients had cycle 1 hematologic dose‐limiting toxicities (DLTs) triggering palbociclib dose reduction to 100 mg daily for 21 days. Two subsequent patients had cycle 1 hematologic DLTs at the reduced dose. Eighty percent of patients had grade 3/4 AEs, including neutropenia (n = 8), white blood cell decreased (n = 7), and thrombocytopenia (n = 5). Serum total IGF‐1 significantly increased (p = 0.013) and ctDNA decreased during the first cycle.ConclusionsThis combination lacks adequate therapeutic activity for further study, though a subset of patients had prolonged stable disease.

While there is a concerted effort to promote physical activity (PA) across United States government and non-governmental organizations, interventions typically focus on aerobic forms of PA, leaving out muscle strengthening PA. The purpose of this study was to operationalize the Reasoned Action Approach (RAA) to explain theory-based correlates of aerobic and muscle strengthening PA, which can provide targets for future public health interventions. Theory-based correlates of both PA behaviors were evaluated using logistic regression analyses, and intentions predicted a significant amount of aerobic PA (14.9%) and muscle strengthening PA (30.7%). Theory-based correlates of intentions to both PA behaviors were evaluated using linear regression analyses, and attitudes, perceived norms, and perceived behavioral control predicted a significant amount for aerobic PA (46.2% to 55.8%) and for muscle strengthening PA (53.9% to 59.8%). Finally, theory-based correlates of attitudes, injunctive norms, descriptive norms and perceived behavioral control were evaluated using salient beliefs, derived from an elicitation study. Results suggest that the RAA is a robust framework for predicting both types of PA behaviors. Belief-based measures also provides guidance for future public health promotion interventions and health communication strategies.

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