A chemoresponse assay for prediction of platinum resistance in primary ovarian cancer

• Published in: American journal of obstetrics and gynecology Vol. 211; no. 1; pp. 68.e1 - 68.e8
• Main Authors: Krivak, Thomas C., MD, Lele, Shashikant, MD, Richard, Scott, MD, Secord, Angeles Alvarez, MD, Leath, Charles A., MD, Brower, Stacey L., PhD, Tian, Chunqiao, PhD, Moore, Richard G., MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2014
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carboplatin - administration & dosage; Carcinoma, Ovarian Epithelial; chemoresponse assay; Chemotherapy, Adjuvant; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Humans; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local - etiology; Neoplasm Recurrence, Local - prevention & control; Neoplasm Staging; Neoplasms, Glandular and Epithelial - drug therapy; Neoplasms, Glandular and Epithelial - pathology; Neoplasms, Glandular and Epithelial - surgery; Obstetrics and Gynecology; ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - pathology; Ovarian Neoplasms - surgery; Paclitaxel - administration & dosage; platinum resistance; Prospective Studies; ROC Curve; Survival Analysis; Treatment Outcome; ovarian cancer; chemoresponse assay; platinum resistance
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2014.02.009

Objective Recurrence following primary platinum-based chemotherapy remains a challenge in the treatment of patients with advanced-stage epithelial ovarian cancer. This study examines whether a chemoresponse assay can identify patients who are platinum-resistant prior to treatment. Study Design Women (n = 276) with International Federation of Gynecology and Obstetrics stage III-IV ovarian, fallopian, and peritoneal cancer were enrolled in an observational study, and the responsiveness of their tumors was evaluated using a chemoresponse assay. All patients were treated with a platinum/taxane regimen following cytoreductive surgery. Assay responses to carboplatin or paclitaxel were classified as sensitive, intermediate sensitive (IS), or resistant. Association of assay response with progression-free survival (PFS) was analyzed using the Kaplan-Meier method and a Cox regression model. Results Patients whose tumors were resistant to carboplatin were at increased risk of disease progression compared to those with nonresistant (sensitive + IS) tumors (median PFS: 11.8 vs 16.6 months, respectively, P < .001), and the association was confirmed after adjusting for other clinical factors (hazard ratio, 1.71; 95% confidence interval, 1.12–2.62; P  = .013). Association of assay response to paclitaxel with PFS trended in multivariate analysis (hazard ratio, 1.28; 95% confidence interval, 0.84–1.95; P  = .245). For tumors resistant to carboplatin, 59% were sensitive or IS to at least 1 other commonly used agent, demonstrating the ability of the assay to inform treatment decisions beyond the standard platinum/taxane regimen. Conclusion Assay resistance to carboplatin is strongly associated with shortened PFS among advanced-stage epithelial ovarian cancer patients treated with carboplatin + paclitaxel therapy, supporting use of this assay to identify patients likely to experience early recurrence on standard platinum-based therapy.