Phase 2 Study of Trabectedin in Patients With Hormone Receptor–Positive, HER-2–Negative, Advanced Breast Carcinoma According to Expression of Xeroderma Pigmentosum G Gene

    loading  Checking for direct PDF access through Ovid



Preclinical and clinical data suggest that xeroderma pigmentosum G gene (XPG) status might predict trabectedin efficacy. This phase 2 study evaluated the efficacy of trabectedin at a dose of 1.3 mg/m2 as a 3-hour intravenous infusion every 3 weeks in hormone receptor–positive, HER-2 (human epidermal growth factor receptor 2)-negative, advanced breast cancer patients according to the tumor level of XPG mRNA expression.

Patients and Methods:

Patients were stratified into high-XPG (>3) or low-XPG (≤ 3) groups. The primary efficacy end point was progression-free survival (PFS) rate at 16 weeks (PFS4); secondary efficacy end points were overall response rate (ORR), duration of response, PFS, overall survival, and safety of trabectedin in this patient population.


Forty-four patients were treated, 21 with high XPG and 23 with low XPG. Four high-XPG and 6 low-XPG patients experienced PFS4; the criterion for further recruitment (> 6 patients experienced PFS4) was thus not met, and recruitment was stopped. One high-XPG patient had a partial response (ORR, 5%). One low-XPG patient had a complete response, and 2 low-XPG patients had partial responses (ORR, 13%). Comparison of efficacy parameters between high-XPG and low-XPG patients showed no statistically significant differences. ORR in the efficacy population was 9.3%, median PFS was 1.9 months, and overall survival was 11.8 months. The safety of trabectedin in breast carcinoma was similar to that shown in other indications.


Trabectedin as single agent had limited activity in hormone-positive, HER-2–negative advanced breast cancer. XPG mRNA expression was not predictive of trabectedin efficacy.


This study evaluated the efficacy and safety of a 3-hour infusion of trabectedin (1.3 mg/m2) once every 3 weeks in hormone receptor–positive, HER-2–negative advanced breast cancer patients according to tumor xeroderma pigmentosum G gene (XPG) mRNA expression levels. Of 44 patients, 4 of 21 with high XPG and 6 of 23 with low XPG experienced progression-free survival at 16 weeks. Tumor XPG mRNA expression was not a predictive marker for trabectedin efficacy. The safety of trabectedin was similar to that shown in other indications.

Related Topics

    loading  Loading Related Articles