Antibody-Drug Conjugate Offers Modest Improvement in Ovarian Cancer

February 9, 2018

Lifastuzumab vedotin offered a modest improvement in progression-free survival over standard care in patients with platinum-resistant ovarian cancer.

An antibody-drug conjugate known as lifastuzumab vedotin offered a numerical but not statistically significant improvement in progression-free survival (PFS) over pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer, according to a new phase II study.

“Single agents approved for platinum-resistant ovarian cancer have overall response rates from 6.5% to 20.5% and a PFS from 2 to 6 months. Thus, there is an urgent need for more effective therapies,” wrote study authors led by Joyce F. Liu, MD, MPH, of the Dana-Farber Cancer Institute in Boston.

Lifastuzumab vedotin (LIFA) is a conjugate of a humanized immunoglobulin G1 anti-NaPi2b monoclonal antibody and the antimitotic agent monomethyl auristatin E. NaPi2b is expressed in ovarian cancer, as well as other malignancies including non–small-cell lung cancer and papillary thyroid cancer; a phase I trial showed that LIFA was well tolerated with potential antitumor activity in platinum-resistant ovarian cancer patients.

The new phase II study included 95 patients randomized to either LIFA given intravenously every 3 weeks (47 patients) or to standard care with pegylated liposomal doxorubicin (PLD); 93 patients received at least one dose of the study drug. Patients were followed for a median of 6.6 months; the results were published in Annals of Oncology.

The median PFS with LIFA was 5.3 months, compared with 3.1 months for PLD, for a hazard ratio (HR) of 0.78 (95% CI, 0.46–1.31; P = .34). In patients with high expression of NaPi2b, the rates were similar, with a median PFS with LIFA of 5.3 months and 3.4 months with PLD, for an HR of 0.71 (95% CI, 0.40–1.26; P = .24).

In the full cohort, the objective response rate to the therapy was 34% with LIFA and 15% with PLD (P = .03). In the NaPi2b-high group, those rates were 36% and 14%, respectively (P = .02). The median duration of response was 5.5 months with LIFA and 3.9 months with PLD in the full cohort.

LIFA was generally well tolerated, with similar numbers of patients in each group reporting adverse events of any grade, grade 3 or higher events, serious events, adverse events leading to therapy discontinuation, and adverse events leading to death. Five LIFA patients (11%) had grade 2 or higher neuropathy, compared with two PLD patients (4%). More LIFA patients had abdominal pain (46% vs 28%), diarrhea (35% vs 19%), and neutropenia (28% vs 17%) vs PLD patients. More PLD patients, meanwhile, had constipation (24% with LIFA vs 38%), stomatitis (7% vs 30%), and palmar-plantar erythrodysesthesia syndrome (0% vs 26%).

“This study was hypothesis generating and was designed to detect only a large benefit of LIFA monotherapy,” the authors wrote, adding that the study confirms that antibody-drug conjugates can have significant clinical activity in platinum-resistant ovarian cancer. “However, this study also highlights that objective response rate alone may not translate to durable responses with [antibody-drug conjugates], and that careful target selection, evaluation of target expression thresholds, response rate, and duration of response may all be important to the future development of antibody-directed cytotoxics in ovarian cancer.”