Randomized phase II trial of carboplatin and paclitaxel with or without lonafarnib in first-line treatment of epithelial ovarian cancer stage IIB-IV.

OBJECTIVES: This study evaluates whether a molecular targeted therapy with the farnesyltransferase inhibitor lonafarnib added to standard chemotherapy in first-line treatment of advanced ovarian cancer (OC) could improve progression-free (PFS) and overall survival (OS). PATIENTS AND METHODS: We performed a prospective randomized phase II study to compare standard therapy carboplatin (C; AUC 5) and paclitaxel (T; 175 mg/m(2)) in primary advanced OC with or without lonafarnib (L). Lonafarnib was given in a dose of 100mg orally twice a day during chemotherapy and was increased afterwards to 200mg up to six months as a maintenance therapy.
RESULTS: 105 patients were recruited (53 patients were randomized to receive LTC, 52 to TC). Hematologic toxicity was similar in both arms. Grade 3 and 4 non-hematological toxicity, occurred significantly more often with LTC (23% versus 4%, p=0.005) and was associated with a higher dropout rate. PFS and OS were not significantly different among both arms. The LTC arm showed inferiority in the stratum with residual tumor of more than 1cm: median PFS was 11.5 months (95% CI: 7.4-14.2) compared with 16.4 (95% CI: 10.3-40.4) for TC (p=0.0141; HR=0.36 (95% CI: 0.15-0.84)) with median OS 20.6 months (95% CI: 13.1-31.0) and 43.4 months (95% CI: 15.7-) for the TC arm (p=0.012; HR=0.32 (95% CI: 0.13-0.8)).
CONCLUSION: The addition of lonafarnib did not improve PFS or OS. Patients with a residual tumor of more than 1cm had significantly shorter PFS and OS. Incorporation of lonafarnib into future studies for primary therapy of OC is not recommended.

RCT Entities:   Population Interventions Outcomes