Veliparib Trial Fails to Improve Outcomes in Ovarian Cancer

Article

Adding the PARP inhibitor veliparib to cyclophosphamide did not improve response rates or progression-free survival in ovarian cancer.

Chemical structure of veliparib

Chemical structure of veliparib

Use of the PARP inhibitor veliparib in combination with oral cyclophosphamide did not result in an improvement in response rate or median progression-free survival compared with treatment with cyclophosphamide alone, according to a phase II study evaluating patients with high-grade serous ovarian cancer, peritoneal, fallopian tube, and BRCA-mutant ovarian cancers.

However, the study did demonstrate that oral cyclophosphamide was well-tolerated among this patient population and was associated with responses and prolonged disease stabilization.

“The relative sensitivity of tumor cells carrying various defects in the homologous recombination (HR) pathway to PARP inhibition is not well characterized, and therefore it is not known whether including patients likely to carry other defects in the HR pathway (high-grade serous ovarian cancer) as well as patients carrying known deleterious mutations in BRCA1 or BRCA2 in a relatively small sample set may have affected the overall outcome of the trial,” Shivaani Kummar, MD, of the National Cancer Institute, and colleagues wrote in Clinical Cancer Research.

“The lack of increased response rate with the addition of veliparib to cyclophosphamide could also be due to the dose of veliparib employed in our study, which was below the 250-400 mg BID doses used in recent trials such as the Gynecologic Oncology Group (GOG) trial of single agent veliparib and others.”

The study included 75 patients who were randomly assigned to cyclophosphamide 50 mg with (n = 38) or without veliparib 60 mg orally (n = 37) in 21-day cycles. Of the 75 patients, 72 were evaluable for response.

There was one complete response reported in each of the treatment arms. Six patients (19.4%) assigned to cyclophosphamide alone had partial response compared with three patients (11.8%) in the combination arm. Four of the patients with responses to cyclophosphamide had BRCA-mutant ovarian cancer, two had high-grade serous ovarian cancer, and one had fallopian tube cancer.

The median progression-free survival was 2.3 months for patients assigned cyclophosphamide alone compared with 2.1 months for combination treatment. Stratification of patients by BRCA status did not reveal any significant improvement in progression-free survival.

The researchers conducted genetic sequence and expression analysis for 211 genes involved in DNA repair; however, none of the genetic alterations were associated with any treatment benefit.

Grade 2/3 leukopenia was the most common adverse events reported among patients in both arms. Two patients assigned to combination treatment reported grade 4 lymphopenia that requiring a dose reduction.

Related Videos
Brian Slomovitz, MD, MS, FACOG discusses the use of new antibody drug conjugates for treating patients with various gynecologic cancers.
Developing novel regimens may continue to improve survival outcomes of patients with advanced cervical cancer following the FDA approval of pembrolizumab and chemoradiation, says Jyoti S. Mayadev, MD.
Treatment with pembrolizumab plus chemoradiation appears to be well tolerated with no detriment to quality of life among those with advanced cervical cancer.
Jyoti S. Mayadev, MD, says that pembrolizumab in combination with chemoradiation will be seamlessly incorporated into her institution’s treatment of those with FIGO 2014 stage III to IVA cervical cancer following the regimen’s FDA approval.
Domenica Lorusso, MD, PhD, says that paying attention to the quality of chemoradiotherapy is imperative to feeling confident about the potential addition of pembrolizumab for locally advanced cervical cancer.
Guidelines from the Society of Gynecologic Oncology may help with managing the ongoing chemotherapy shortage in the treatment of patients with gynecologic cancers, according to Brian Slomovitz, MD, MS, FACOG.
Interim data reveal favorable responses in patients with low-grade serous ovarian cancer treated with avutometinib plus defactinib, according to Susana N. Banerjee, MD.
Brian Slomovitz, MD, MS, FACOG, notes that sometimes there is a need to substitute cisplatin for carboplatin, and vice versa, to best manage gynecologic cancers during the chemotherapy shortage.
Findings from the phase 3 MIRASOL trial support mirvetuximab soravtansine as a standard treatment option for platinum-resistant ovarian cancer, according to Ritu Salani, MD.
Trastuzumab deruxtecan appears to elicit ‘impressive’ responses among patients with HER2-positive gynecologic cancers regardless of immunohistochemistry in the phase 2 DESTINY-PanTumor02 trial.
Related Content