Platinum versus platinum-combination chemotherapy in platinum-sensitive recurrent ovarian cancer: a meta-analysis using individual patient data

• Published in: Annals of oncology Vol. 24; no. 12; pp. 3028 - 3034
• Main Authors: Raja, F.A., Counsell, N., Colombo, N., Pfisterer, J., du Bois, A., Parmar, M.K., Vergote, I.B., Gonzalez-Martin, A., Alberts, D.S., Plante, M., Torri, V., Ledermann, J.A.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.12.2013; Oxford University Press
• Subjects: Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carboplatin - administration & dosage; Cisplatin - administration & dosage; Disease-Free Survival; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; IPD meta-analysis; Kaplan-Meier Estimate; Medical sciences; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - mortality; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - mortality; Pharmacology. Drug treatments; Randomized Controlled Trials as Topic; recurrent ovarian cancer; Treatment Outcome; Tumors; IPD meta-analysis; recurrent ovarian cancer; Human; Drug combination; Relapse; Ovary cancer; Malignant tumor; Female genital diseases; Metaanalysis; Ovarian diseases; Platinum; Combined treatment; Comparative study; Cancer
• ISSN: 0923-7534; 1569-8041; 1569-8041
• DOI: 10.1093/annonc/mdt406

The majority of women with ovarian cancer develop recurrent disease. For patients with a platinum-free interval of >6 months, platinum-based chemotherapy is a treatment of choice. The benefit of platinum-based combination chemotherapy in randomized trials varies, and a meta-analysis was carried out to gain more secure information on the size of the benefit of this treatment. We initiated a systematic review and meta-analysis following a pre-specified protocol to determine whether combination chemotherapy is superior to single-agent platinum chemotherapy in women with relapsed platinum-sensitive ovarian cancer. A total of five potentially eligible randomized trials were identified that had used combination-platinum chemotherapy versus single-agent platinum chemotherapy in women with relapsed platinum-sensitive ovarian cancer. For one trial (190 patients), adequate contact with the investigators could not be established. Therefore, four trials that randomly assigned 1300 patients were included, with a median follow-up of 36.1 months. Overall survival (OS) analyses were based on 865 deaths and demonstrated evidence for the benefit of combination-platinum chemotherapy (HR = 0.80; 95% CI, 0.64–1.00; P = 0.05). Progression-free survival (PFS) analyses were based on 1167 events and demonstrated strong evidence for the benefit of combination-platinum chemotherapy (HR = 0.68; 95% CI, 0.57–0.81; P < 0.001). There was no evidence of a difference in the relative effect of combination-platinum chemotherapy on either OS or PFS in patient subgroups defined by previous paclitaxel (Taxol) treatment (OS, P = 0.49; PFS, P = 0.66), duration of treatment-free interval (OS, P = 0.86; PFS, P = 0.48) or the number of previous lines of chemotherapy (OS, P = 0.21; PFS, P = 0.27). In this individual patient data (IPD) meta-analysis, we have demonstrated that combination-platinum chemotherapy improves OS and PFS across all subgroups. This provides the strongest evidence to date of the benefit of combination-platinum over single-agent platinum.