Farletuzumab may benefit patients with ovarian cancer and low CA-125 level

For patients with epithelial ovarian cancer in a platinum-sensitive first relapse, farletuzumab combined with carboplatin and taxane improved progression-free survival (PFS) and overall survival (OS) in a prespecified subgroup of patients with lower baseline levels of CA-125.

Primary analysis of the intention-to-treat population showed no significant difference in median PFS for placebo, farletuzumab at 1.25 mg/kg, and farletuzumab at 2.5 mg/kg (9.0, 9.5, and 9.7 months, respectively). However, in a prespecified subgroup analysis, patients with CA-125 not more than three times the upper limit of normal who received farletuzumab at 2.5 mg/kg had significantly improved PFS: median 13.6 months vs. 8.8 months for the placebo arm (hazard ratio, 0.49; P = .003).

“Despite these subgroup results not being a confirmatory statistical analysis according to ICH E9 guidelines, the observations warrant additional preclinical and clinical investigation,” wrote Dr. Ignace Vergote, professor in the department of gynecologic oncology at the Catholic University of Leuven, Belgium, and his colleagues. “Higher CA-125 levels may directly inhibit the immune response of farletuzumab-mediated [antibody-dependent cellular cytotoxicity] by suppressing natural killer-cell function; therefore, patients with lower CA-125 levels may exhibit a stronger farletuzumab mediated immune response,” they added (J Clin Oncol. 2016 Mar 21. doi:10.1200/JCO.2015.63.2596).

Patients with serum concentrations of farletuzumab above median levels of 57 mcg/mL had significantly improved PFS (HR, 0.679; 95% confidence interval, 0.55-0.83; P = .002). The investigators suggested that some patients may not accumulate adequate antibody levels to produce a pharmacologic effect, and they suggested that, given the observed absence of dose-limiting toxicities, higher doses of farletuzumab should be tested.

The randomized, double-blind, phase III study (MORAb-003-004) included 1,091 women with epithelial ovarian cancer in a platinum-sensitive first relapse: 361 received placebo, 367 received farletuzumab 1.25 mg/kg, and 363 received farletuzumab 2.5 mg/kg.

Overall safety profiles were similar for the three treatment arms. The most common adverse events were alopecia, nausea, neutropenia, fatigue, thrombocytopenia, and neuropathy. Anemia was more frequent in the farletuzumab groups (42.1%, 37.0%, 34.9% for farletuzumab 2.5 mg/kg, farletuzumab 1.25 mg/kg, and placebo, respectively).

For patients with epithelial ovarian cancer in a platinum-sensitive first relapse, farletuzumab combined with carboplatin and taxane improved progression-free survival (PFS) and overall survival (OS) in a prespecified subgroup of patients with lower baseline levels of CA-125.

Primary analysis of the intention-to-treat population showed no significant difference in median PFS for placebo, farletuzumab at 1.25 mg/kg, and farletuzumab at 2.5 mg/kg (9.0, 9.5, and 9.7 months, respectively). However, in a prespecified subgroup analysis, patients with CA-125 not more than three times the upper limit of normal who received farletuzumab at 2.5 mg/kg had significantly improved PFS: median 13.6 months vs. 8.8 months for the placebo arm (hazard ratio, 0.49; P = .003).

“Despite these subgroup results not being a confirmatory statistical analysis according to ICH E9 guidelines, the observations warrant additional preclinical and clinical investigation,” wrote Dr. Ignace Vergote, professor in the department of gynecologic oncology at the Catholic University of Leuven, Belgium, and his colleagues. “Higher CA-125 levels may directly inhibit the immune response of farletuzumab-mediated [antibody-dependent cellular cytotoxicity] by suppressing natural killer-cell function; therefore, patients with lower CA-125 levels may exhibit a stronger farletuzumab mediated immune response,” they added (J Clin Oncol. 2016 Mar 21. doi:10.1200/JCO.2015.63.2596).

Patients with serum concentrations of farletuzumab above median levels of 57 mcg/mL had significantly improved PFS (HR, 0.679; 95% confidence interval, 0.55-0.83; P = .002). The investigators suggested that some patients may not accumulate adequate antibody levels to produce a pharmacologic effect, and they suggested that, given the observed absence of dose-limiting toxicities, higher doses of farletuzumab should be tested.

The randomized, double-blind, phase III study (MORAb-003-004) included 1,091 women with epithelial ovarian cancer in a platinum-sensitive first relapse: 361 received placebo, 367 received farletuzumab 1.25 mg/kg, and 363 received farletuzumab 2.5 mg/kg.

Overall safety profiles were similar for the three treatment arms. The most common adverse events were alopecia, nausea, neutropenia, fatigue, thrombocytopenia, and neuropathy. Anemia was more frequent in the farletuzumab groups (42.1%, 37.0%, 34.9% for farletuzumab 2.5 mg/kg, farletuzumab 1.25 mg/kg, and placebo, respectively).

For patients with epithelial ovarian cancer in a platinum-sensitive first relapse, farletuzumab combined with carboplatin and taxane improved progression-free survival (PFS) and overall survival (OS) in a prespecified subgroup of patients with lower baseline levels of CA-125.

Primary analysis of the intention-to-treat population showed no significant difference in median PFS for placebo, farletuzumab at 1.25 mg/kg, and farletuzumab at 2.5 mg/kg (9.0, 9.5, and 9.7 months, respectively). However, in a prespecified subgroup analysis, patients with CA-125 not more than three times the upper limit of normal who received farletuzumab at 2.5 mg/kg had significantly improved PFS: median 13.6 months vs. 8.8 months for the placebo arm (hazard ratio, 0.49; P = .003).

“Despite these subgroup results not being a confirmatory statistical analysis according to ICH E9 guidelines, the observations warrant additional preclinical and clinical investigation,” wrote Dr. Ignace Vergote, professor in the department of gynecologic oncology at the Catholic University of Leuven, Belgium, and his colleagues. “Higher CA-125 levels may directly inhibit the immune response of farletuzumab-mediated [antibody-dependent cellular cytotoxicity] by suppressing natural killer-cell function; therefore, patients with lower CA-125 levels may exhibit a stronger farletuzumab mediated immune response,” they added (J Clin Oncol. 2016 Mar 21. doi:10.1200/JCO.2015.63.2596).

Patients with serum concentrations of farletuzumab above median levels of 57 mcg/mL had significantly improved PFS (HR, 0.679; 95% confidence interval, 0.55-0.83; P = .002). The investigators suggested that some patients may not accumulate adequate antibody levels to produce a pharmacologic effect, and they suggested that, given the observed absence of dose-limiting toxicities, higher doses of farletuzumab should be tested.

The randomized, double-blind, phase III study (MORAb-003-004) included 1,091 women with epithelial ovarian cancer in a platinum-sensitive first relapse: 361 received placebo, 367 received farletuzumab 1.25 mg/kg, and 363 received farletuzumab 2.5 mg/kg.

Overall safety profiles were similar for the three treatment arms. The most common adverse events were alopecia, nausea, neutropenia, fatigue, thrombocytopenia, and neuropathy. Anemia was more frequent in the farletuzumab groups (42.1%, 37.0%, 34.9% for farletuzumab 2.5 mg/kg, farletuzumab 1.25 mg/kg, and placebo, respectively).