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- Kurzeder, Christian, et al.
(författare)
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Double-blind, placebo-controlled, randomized phase III trial evaluating pertuzumab combined with chemotherapy for low tumor human epidermal growth factor receptor 3 mRNA-Expressing platinum-resistant ovarian Cancer (PENELOPE)
- 2016
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 34:21, s. 25-2516
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The AGO-OVAR 2.29/ENGOT-ov14/PENELOPE prospectively randomized phase III trial evaluated the addition of pertuzumab to chemotherapy in patients with platinum-resistant ovarian carcinoma with low tumor human epidermal growth factor receptor 3 (HER3)mRNA expression. We report the results of the primary efficacy analysis. Patients and Methods Eligible patients had ovarian carcinoma that progressed during or within 6 months of completing four or more platinum cycles, centrally tested low tumor HER3 mRNA expression (concentration ratio # 2.81 by quantitative reverse transcriptase polymerase chain reaction on cobas z480 [Roche Molecular Diagnostics, Pleasanton, CA]), and no more than two prior lines of chemotherapy. After investigators selection of the chemotherapy backbone (single-agent topotecan, weekly paclitaxel, or gemcitabine), patientswere randomly assigned to also receive either placebo or pertuzumab (840-mg loading dose followed by 420 mg every 3 weeks). Stratification factors were selected chemotherapy, prior antiangiogenic therapy, and platinum-free interval. The primary end point was independent review committee-assessed progression-free survival (PFS). Additional end points included overall survival, investigator-assessed PFS, objective response rate, safety, patient-reported outcomes, and translational research. Results Overall, 156 patientswere randomly assigned. Adding pertuzumab to chemotherapy did not significantly improve independent review committee-assessed PFS for the primary analysis (stratified hazard ratio, 0.74; 95% CI, 0.50 to 1.11; P = .14; median PFS, 4.3 months for pertuzumab plus chemotherapy v 2.6 months for placebo plus chemotherapy). Sensitivity analyses and secondary efficacy end point results were consistent with the primary analysis. The effect on PFS favoring pertuzumab was more pronounced in the gemcitabine and paclitaxel cohorts. No new safety signals were seen. Conclusion Although the primary objective was not met, subgroup analyses showed trends in PFS favoring pertuzumab in the gemcitabine and paclitaxel cohorts, meriting further exploration of pertuzumab in ovarian cancer.
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- Sehouli, Jalid, et al.
(författare)
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Catumaxomab with and without prednisolone premedication for the treatment of malignant ascites due to epithelial cancer: results of the randomised phase IIIb CASIMAS study
- 2014
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Ingår i: Medical Oncology. - : Humana Press. - 1357-0560 .- 1559-131X. ; 31:8, s. 76-
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Tidskriftsartikel (refereegranskat)abstract
- This two-arm, randomised, multicentre, open-label, phase IIIb study investigated the safety and efficacy of a 3-h catumaxomab infusion with/without prednisolone premedication to reduce catumaxomab-related adverse events. Patients with malignant ascites due to epithelial cancer received four 3-h intraperitoneal catumaxomab infusions with/without intravenous prednisolone (25 mg) premedication before each infusion. The primary safety endpoint was a composite safety score calculated from the incidence and intensity of the most frequent catumaxomab-related adverse events (pyrexia, nausea, vomiting and abdominal pain). Puncture-free survival (PuFS) was a co-primary endpoint. Time to next puncture (TTPu) and overall survival (OS) were secondary endpoints. Prednisolone premedication did not result in a significant reduction in the main catumaxomab-related adverse events. The mean composite safety score was comparable in both arms (catumaxomab plus prednisolone, 4.1; catumaxomab, 3.8; p = 0.383). Median PuFS (30 vs. 37 days) and TTPu (78 vs. 102 days) were shorter in the catumaxomab plus prednisolone arm than in the catumaxomab arm, but the differences were not statistically significant (p = 0.402 and 0.599, respectively). Median OS was longer in the catumaxomab plus prednisolone arm than in the catumaxomab arm (124 vs. 86 days), but the difference was not statistically significant (p = 0.186). The superiority of catumaxomab plus prednisolone versus catumaxomab alone could not be proven for the primary endpoint. Prednisolone did not result in a significant reduction in the main catumaxomab-related adverse events. The study confirms the safety and efficacy of catumaxomab administered as four 3-h intraperitoneal infusions for the treatment of malignant ascites.
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