Farletuzumab Tested For Recurrent Platinum-Sensitive Ovarian Cancer

Farletuzumab fails to improve survival outcomes over platinum-based chemotherapy alone in ovarian cancer patients overall but may have potential for women with a low CA-125 value

medwireNews: Treatment with a humanised monoclonal antibody to folate receptor-α (FRA) does not improve progression-free survival (PFS) in women undergoing chemotherapy for recurrent platinum-sensitive ovarian cancer, phase III trial results show.

However, subgroup analysis indicated that patients with a CA-125 level no more than three times the upper limit of normal – indicative of a low volume of residual disease – might benefit from farletuzumab, the researchers report in the Journal of Clinical Oncology.

The primary outcome of PFS was 9.5 and 9.7 months for the 376 and 363 patients randomly assigned to receive farletuzumab at the 1.25 mg/kg and 2.5 mg/kg doses, respectively, compared with 9.0 months for the 352 patients given placebo.

All participants received farletuzumab until disease progression, as well as six cycles of paclitaxel or docetaxel, explain Ignace Vergote, from University Hospital Leuven in Belgium, and co-investigators.

But among patients with a baseline serum CA-125 level no more than three times the upper limit of normal, PFS was significantly longer for patients treated with the 2.5 mg/kg dose of farletuzumab than those given placebo, at a median 13.6 versus 8.8 months and a hazard ratio (HR) of 0.49.

Overall survival was also significantly improved with the higher dose of the immunotherapy, with a non-estimable median value for the active treatment group versus 29.1 months for placebo, giving an HR of 0.44.

In addition, exposure analysis suggested that patients who had an average minimum serum farletuzumab concentration above the median value of 57.6 μg/mL had better PFS than those given placebo (HR=0.68), regardless of actual dose assigned.

The researchers explain that CA-125 is hypothesised to reduce the efficacy of immunotherapeutic antibodies by suppressing natural kill cell function. “Therefore, higher levels of CA-125 may disrupt the ability of farletuzumab to elicit an immune response, thereby lowering its anti-FRA-mediated tumor-killing potential”, they write.

The most common reported adverse events were associated with the chemotherapy regimen, although patients given farletuzumab 2.5 mg/kg had a higher rate of anaemia than those given the lower dose or placebo (42.1 vs 34.9 and 37.0%, respectively).

During single-agent maintenance, grade 3 or higher adverse events were reported by a comparable 16.5%, 17.6% and 17.9% of patients in the 2.5 mg/kg, 1.25 mg/kg and placebo groups, respectively.

“Given this safety profile, a higher dose of farletuzumab should likely be possible without undue intolerance by the patient”, say Ignace Vergote and co-authors.

They conclude: “Based on the results of this phase III study, a follow-on study in patients with platinum-sensitive [epithelial ovarian cancers] who have low CA-125 levels is planned using a modified farletuzumab dosing regimen.”


Vergote I, Armstrong D, Scambia G, et al. A randomized, double-blind, placebo-controlled, phase III study to assess efficacy and safety of weekly farletuzumab in combination with carboplatin and taxane in patients with ovarian cancer in first platinum-sensitive relapse. J Clin Oncol 2016; Advance online publication 21 March. doi: 10.1200/JCO.2015.63.2596

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