Purpose: Tumor necrosis factor (TNF) ␣ is a key player in the tumor microenvironment and is involved in the pathogenesis of breast cancer. Etanercept is a recombinant human soluble p75 TNF receptor that binds to TNF-␣ and renders it biologically unavailable. In the current study, we sought to determine the toxicity, biological activity, and therapeutic efficacy of Etanercept in metastatic breast cancer.Experimental Design: We initiated a Phase II, nonrandomized, open-labeled study in patients with progressive metastatic breast cancer refractory to conventional therapy (Phase I toxicity data were available in patients with rheumatoid arthritis). Etanercept was administered subcutaneously at a dose of 25 mg twice weekly until disease progression.Results: Sixteen patients were recruited [median age 53 years (range, 34 to 74)]. A total of 141.6 weeks of therapy was administered (median of 8.1 weeks). Seven patients received >12 weeks of therapy. The most common side effects were injection site reactions (6), fatigue (5), loss of appetite (2), nausea (1), headache (1), and dizziness (1). Brief period of disease stabilization was seen in 1 patient lasting for 16.4 weeks. Immunoreactive TNF-␣ was elevated within 24 hours of therapy and persisted until the end of treatment (days 7, 28, 56, and 84). Phytohemagglutinin stimulates the production of interleukin-6 and CCL2 in peripheral blood cells, and the ability of Etanercept to modulate this response was assessed in a cytokine release assay. A consistent decrease in interleukin-6 and CCL2 level was seen compared with pretreatment values in serial blood samples (days 1, 7, 28, 56, and 84).Conclusions: Our study shows the safety and biological activity of Etanercept in breast cancer and provides data to assess pharmacodynamic endpoints of different schedules of Etanercept and combinations with chemotherapy or other biological therapies.
We provide evidence for the biologic activity and safety of etanercept in recurrent ovarian cancer. Our data suggest possible clinical activity that must be confirmed in future studies.
IntroductionIt has been recognized that increasing body mass index (BMI) is associated with improved outcome from immune checkpoint inhibitors (ICIs) in patients with various malignancies including non-small cell lung cancer (NSCLC). However, it is unclear whether baseline BMI may influence outcomes from first-line chemoimmunotherapy combinations.MethodsIn this international multicenter study, we evaluated the association between baseline BMI, progression-free survival (PFS) and overall survival (OS) in a cohort of patients with stage IV NSCLC consecutively treated with first-line chemoimmunotherapy combinations. BMI was categorized according to WHO criteria.ResultsAmong the 853 included patients, 5.3% were underweight; 46.4% were of normal weight; 33.8% were overweight; and 14.5% were obese. Overweight and obese patients were more likely aged ≥70 years (p=0.00085), never smokers (p<0.0001), with better baseline Eastern Cooperative Oncology Group—Performance Status (p=0.0127), and had lower prevalence of central nervous system (p=0.0002) and liver metastases (p=0.0395). Univariable analyses showed a significant difference in the median OS across underweight (15.5 months), normal weight (14.6 months), overweight (20.9 months), and obese (16.8 months) patients (log-rank: p=0.045, log rank test for trend: p=0.131), while no difference was found with respect to the median PFS (log-rank for trend: p=0.510). Neither OS nor PFS was significantly associated with baseline BMI on multivariable analysis.ConclusionsIn contrast to what was observed in the context of chemotherapy-free ICI-based regimens, baseline BMI does not affect clinical outcomes from chemoimmunotherapy combinations in patients with advanced NSCLC.
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