|Title||Multicenter Phase II Study of Cabazitaxel in Advanced Gastroesophageal Cancer: Association of HER2 Expression and M2-Like Tumor-Associated Macrophages with Patient Outcome.|
|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Shah MA, Enzinger P, Ko AH, Ocean AJ, Philip PAgop, Thakkar PV, Cleveland K, Lu Y, Kortmansky J, Christos PJ, Zhang C, Kaur N, Elmonshed D, Galletti G, Sarkar S, Bhinder B, Pittman ME, Plotnikova OMikhaylovn, Kotlov N, Frenkel F, Bagaev A, Elemento O, Betel D, Giannakakou P, Lenz H-J|
|Journal||Clin Cancer Res|
|Date Published||2020 09 15|
PURPOSE: We examined cabazitaxel, a novel next-generation taxoid, in patients with metastatic gastric cancer in a multicenter phase II study.
PATIENTS AND METHODS: Patients who have progressed on one or more prior therapies for locally advanced, unresectable, or metastatic disease were eligible, and prior taxane therapy was allowed. Taxane-naïve and pretreated cohorts were analyzed independently for efficacy. The primary endpoint for both cohorts was progression-free survival (PFS) using RECIST 1.1, using a Simon's two-stage design (10% significance and 80% power) for both cohorts. Comprehensive molecular annotation included whole exome and bulk RNA sequencing.
RESULTS: Fifty-three patients enrolled in the taxane-naïve cohort (Arm A) and 23 patients in the prior-taxane cohort (Arm B), from January 8, 2013, to April 8, 2015: median age 61.7 years (range, 35.5-91.8 years), 66% male, 66% Caucasian. The most common adverse events included neutropenia (17% Arm A and 39% Arm B), fatigue/muscle weakness (13%), and hematuria (12%). In Arm A, the 3-month PFS rate was 28% [95% confidence interval (CI), 17%-42%] and did not meet the prespecified efficacy target. The 3-month PFS rate in Arm B was 35% (95% CI, 16%-57%) and surpassed its efficacy target. HER2 amplification or overexpression was associated with improved disease control ( = 0.003), PFS ( = 0.04), and overall survival ( = 0.002). An M2 macrophage signature was also associated with improved survival ( = 0.031).
CONCLUSIONS: Cabazitaxel has modest activity in advanced gastric cancer, including in patients previously treated with taxanes. Her2 amplification/overexpression and M2 high macrophage signature are potential biomarkers for taxane efficacy that warrant further evaluation.
|Alternate Journal||Clin Cancer Res|
|PubMed Central ID||PMC8209413|
|Grant List||R01 CA228512 / CA / NCI NIH HHS / United States|