OBJECTIVE: A new treatment principle, which seems to radically change the treatment approach in ovarian cancer (OC), has developed over the past few years. Poly(ADP-ribose) polymerase inhibitors work by interfering with mechanisms important to DNA damage repair. Cancer cells that already have defects in the BRCA genes are particularly sensitive to treatment with poly(ADP-ribose) polymerase inhibitors. The main purpose of this study was to investigate the effect of veliparib in patients with known BRCA1/2 mutations and with a platinum-resistant or intermediate sensitive relapse of OC. METHODS: Major eligibility criteria were primary epithelial ovarian/fallopian/peritoneal cancer patients with a platinum-resistant or intermediate sensitive relapse of OC and with evaluable disease by either Response Evaluation Criteria In Solid Tumors or Gynecological Cancer Intergroup CA-125 criteria. Patients were treated with oral veliparib twice daily on days 1 to 28. RESULTS: Sixteen patients were enrolled in the phase I part, and a maximum tolerable dose of 300 mg twice daily was established. The phase II part enrolled 32 patients with a median of 4 previous treatment regimens. The overall response rate combining Response Evaluation Criteria In Solid Tumors and CA-125 response was 65% (6% complete response and 59% partial response). Progression-free and overall survival rates of the intention-to-treat population were 5.6 months (95% confidence interval, 5.2-7.3 months) and 13.7 months (95% confidence interval, 10.2-17.3 months), respectively. The most common phase II treatment-related grade 2 toxicities included fatigue (22%), nausea (22%), and vomiting (9%). CONCLUSIONS: Treatment with veliparib in heavily pretreated patients with relapse of OC demonstrates a considerable efficacy with an acceptable toxicity profile.
OBJECTIVE: A new treatment principle, which seems to radically change the treatment approach in ovarian cancer (OC), has developed over the past few years. Poly(ADP-ribose) polymerase inhibitors work by interfering with mechanisms important to DNA damage repair. Cancer cells that already have defects in the BRCA genes are particularly sensitive to treatment with poly(ADP-ribose) polymerase inhibitors. The main purpose of this study was to investigate the effect of veliparib in patients with known BRCA1/2 mutations and with a platinum-resistant or intermediate sensitive relapse of OC. METHODS: Major eligibility criteria were primary epithelial ovarian/fallopian/peritoneal cancerpatients with a platinum-resistant or intermediate sensitive relapse of OC and with evaluable disease by either Response Evaluation Criteria In Solid Tumors or Gynecological Cancer Intergroup CA-125 criteria. Patients were treated with oral veliparib twice daily on days 1 to 28. RESULTS: Sixteen patients were enrolled in the phase I part, and a maximum tolerable dose of 300 mg twice daily was established. The phase II part enrolled 32 patients with a median of 4 previous treatment regimens. The overall response rate combining Response Evaluation Criteria In Solid Tumors and CA-125 response was 65% (6% complete response and 59% partial response). Progression-free and overall survival rates of the intention-to-treat population were 5.6 months (95% confidence interval, 5.2-7.3 months) and 13.7 months (95% confidence interval, 10.2-17.3 months), respectively. The most common phase II treatment-related grade 2 toxicities included fatigue (22%), nausea (22%), and vomiting (9%). CONCLUSIONS: Treatment with veliparib in heavily pretreated patients with relapse of OC demonstrates a considerable efficacy with an acceptable toxicity profile.
Authors: Robert L Coleman; Gini F Fleming; Mark F Brady; Elizabeth M Swisher; Karina D Steffensen; Michael Friedlander; Aikou Okamoto; Kathleen N Moore; Noa Efrat Ben-Baruch; Theresa L Werner; Noelle G Cloven; Ana Oaknin; Paul A DiSilvestro; Mark A Morgan; Joo-Hyun Nam; Charles A Leath; Shibani Nicum; Andrea R Hagemann; Ramey D Littell; David Cella; Sally Baron-Hay; Jesus Garcia-Donas; Mika Mizuno; Katherine Bell-McGuinn; Danielle M Sullivan; Bruce A Bach; Sudipta Bhattacharya; Christine K Ratajczak; Peter J Ansell; Minh H Dinh; Carol Aghajanian; Michael A Bookman Journal: N Engl J Med Date: 2019-09-28 Impact factor: 91.245
Authors: Robert D Morgan; Andrew R Clamp; D Gareth R Evans; Richard J Edmondson; Gordon C Jayson Journal: Cancer Chemother Pharmacol Date: 2018-02-20 Impact factor: 3.333