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.
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/m2as 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 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.
Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: ahmad.awada@bordet.be.
Ahmad
A
Awada
Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Javier
J
Cortés
Hospital General Universitario and Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
Miguel
M
Martín
Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Philippe
P
Aftimos
Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Mafalda
M
Oliveira
Hospital General Universitario and Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
Sara
S
López-Tarruella
Hopital Sant Louis, Paris, France.
Marc
M
Espie
Pharma-Mar, Clinical R&D, Colmenar Viejo, Madrid, Spain.
Pilar
P
Lardelli
Pharma-Mar, Clinical R&D, Colmenar Viejo, Madrid, Spain.
Sonia
S
Extremera
Pharma-Mar, Clinical R&D, Colmenar Viejo, Madrid, Spain.
Eva M
EM
Fernández-García
Institut Gustave Roussy, Villejuif, France.
Suzette
S
Delaloge
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004149:Dioxoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016019:Survival Analysis; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077606:Trabectedin; D014157:Transcription Factors / Q000378:metabolism*; D016896:Treatment Outcome; D000099250:DNA Excision Repair Protein ERCC-5
D018906:Antineoplastic Agents, Alkylating; D054316:Biomarkers, Pharmacological; D004268:DNA-Binding Proteins; D004149:Dioxoles; D004720:Endonucleases; D009687:Nuclear Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5; C508053:ERBB2 protein, human
Breast carcinoma; HER2 negative; Hormone receptor positive; Predictive markers; XPG