Prognostic Value of Human Epidermal Growth Factor Receptor 2 (Her-2)/neu in Patients With Advanced Ovarian Cancer Treated With Platinum/Paclitaxel as First-Line Chemotherapy: A Retrospective Evaluation of the AGO-OVAR 3 Trial by the AGO OVAR Germany

2009 ◽  
Vol 19 (1) ◽  
pp. 109-115 ◽  
Author(s):  
Jacobus Pfisterer ◽  
Andreas Du Bois ◽  
Eva-Katrin Bentz ◽  
Friedrich Kommoss ◽  
Philipp Harter ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Prognostic Value ◽  
Growth Factor Receptor ◽  
Advanced Ovarian Cancer ◽  
Advanced Stage ◽  
First Line ◽  
Her 2 ◽  
Epidermal Growth ◽  
Line Chemotherapy

Objectives:Results on the prognostic value of human epidermal growth factor receptor 2 (HER-2)/neu in ovarian cancer are inconsistent. This exploratory analysis evaluates Her-2/neu as a prognostic factor in a large cohort of patients with advanced-stage ovarian cancer treated with platinum/paclitaxel as first-line chemotherapy within a prospective randomized trial.Methods:Her-2/neu expression was assessed by immunohistochemistry in 359 patients (46%) treated within the AGO-OVAR 3 trial (n = 783). Patients received either cisplatin/paclitaxel or carboplatin/paclitaxel according to the study protocol. Immunohistochemistry results were scored according to the Dako score.Results:Her-2/neu Dako scores of 0 or 1+ was found in 337 patients (94%) and a score of 2+ or 3+ in 22 patients (6%). Her-2/neu overexpression (2+/3+) was associated with a higher International Federation of Gynecology and Obstetrics stage and larger postoperative residual disease. There were no significant differences in response to chemotherapy between the Her-2/neu score subgroups and in progression-free survival time. In a multivariate analysis, the Her-2/neu score had no significant impact on overall survival time.Conclusions:In the present study, Her-2/neu overexpression in patients with advanced-stage ovarian cancer was rare and provided no evidence for a prognostic value of Her-2/neu in patients with advanced ovarian cancer treated with platinum/paclitaxel.

Incorporation of Pazopanib in Maintenance Therapy of Ovarian Cancer

2014 ◽  
Vol 32 (30) ◽  
pp. 3374-3382 ◽  
Author(s):  
Andreas du Bois ◽  
Anne Floquet ◽  
Jae-Weon Kim ◽  
Joern Rau ◽  
Josep M. del Campo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Growth Factor Receptor ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Line Chemotherapy

PurposePazopanib is an oral, multikinase inhibitor of vascular endothelial growth factor receptor (VEGFR) -1/-2/-3, platelet-derived growth factor receptor (PDGFR) -α/-β, and c-Kit. Preclinical and clinical studies support VEGFR and PDGFR as targets for advanced ovarian cancer treatment. This study evaluated the role of pazopanib maintenance therapy in patients with ovarian cancer whose disease did not progress during first-line chemotherapy.Patients and MethodsNine hundred forty patients with histologically confirmed cancer of the ovary, fallopian tube, or peritoneum, International Federation Gynecology Obstetrics (FIGO) stages II-IV, no evidence of progression after primary therapy consisting of surgery and at least five cycles of platinum-taxane chemotherapy were randomized 1:1 to receive pazopanib 800 mg once per day or placebo for up to 24 months. The primary end point was progression-free survival by RECIST 1.0 assessed by the investigators.ResultsMaintenance pazopanib prolonged progression-free survival compared with placebo (hazard ratio [HR], 0.77; 95% CI, 0.64 to 0.91; P = .0021; median, 17.9 v 12.3 months, respectively). Interim survival analysis based on events in 35.6% of the population did not show any significant difference. Grade 3 or 4 adverse events of hypertension (30.8%), neutropenia (9.9%), liver-related toxicity (9.4%), diarrhea (8.2%), fatigue (2.7%), thrombocytopenia (2.5%), and palmar-plantar erythrodysesthesia (1.9%) were significantly higher in the pazopanib arm. Treatment discontinuation related to adverse events was higher among patients treated with pazopanib (33.3%) compared with placebo (5.6%).ConclusionPazopanib maintenance therapy provided a median improvement of 5.6 months (HR, 0.77) in progression-free survival in patients with advanced ovarian cancer who have not progressed after first-line chemotherapy. Overall survival data to this point did not suggest any benefit. Additional analysis should help to identify subgroups of patients in whom improved efficacy may balance toxicity (NCT00866697).

scholarly journals Phase III, Double-Blind, Randomized Study Comparing Lapatinib Plus Paclitaxel With Placebo Plus Paclitaxel As First-Line Treatment for Metastatic Breast Cancer

2008 ◽  
Vol 26 (34) ◽  
pp. 5544-5552 ◽  
Author(s):  
Angelo Di Leo ◽  
Henry L. Gomez ◽  
Zeba Aziz ◽  
Zanete Zvirbule ◽  
Jose Bines ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Phase Iii ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Her 2 ◽  
Epidermal Growth

PurposeLapatinib, a dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER-2/ErbB2), is effective against HER-2–positive locally advanced or metastatic breast cancer (MBC). This phase III trial evaluated the efficacy of lapatinib in HER-2–negative and HER-2–uncharacterized MBC.Patients and MethodsWomen with MBC were randomly assigned to first-line therapy with paclitaxel 175 mg/m2every 3 weeks plus lapatinib 1,500 mg/d or placebo. A preplanned retrospective evaluation of HER-2 status was performed using fluorescence in situ hybridization and immunohistochemistry. The primary end point was time to progression (TTP); secondary end points were objective response rate (ORR), clinical benefit rate (CBR), event-free survival (EFS), and overall survival (OS).ResultsIn the intent-to-treat population (n = 579), there were no significant differences in TTP, EFS, or OS between treatment arms, although differences in ORR and CBR were noted. In 86 HER-2–positive patients (15%), treatment with paclitaxel-lapatinib resulted in statistically significant improvements in TTP, EFS, ORR, and CBR compared with paclitaxel-placebo. No differences between treatment groups were observed for any end point in HER-2–negative patients. The most common adverse events were alopecia, rash, and diarrhea. The incidence of diarrhea and rash was significantly higher in the paclitaxel-lapatinib arm. The rate of cardiac events was low, and no difference was observed between treatment arms.ConclusionPatients with HER-2–negative or HER-2–untested MBC did not benefit from the addition of lapatinib to paclitaxel. However, first-line therapy with paclitaxel-lapatinib significantly improved clinical outcomes in HER-2–positive patients. Prospective evaluation of the efficacy and safety of this combination is ongoing in early and metastatic HER-2–positive breast cancer patients.

scholarly journals Phase III, Double-Blind, Randomized Trial That Compared Maintenance Lapatinib Versus Placebo After First-Line Chemotherapy in Patients With Human Epidermal Growth Factor Receptor 1/2–Positive Metastatic Bladder Cancer

2017 ◽  
Vol 35 (1) ◽  
pp. 48-55 ◽  
Author(s):  
Thomas Powles ◽  
Robert A. Huddart ◽  
Tony Elliott ◽  
Shah-Jalal Sarker ◽  
Charlotte Ackerman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
First Line ◽  
Her2 Positive ◽  
Epidermal Growth ◽  
Line Chemotherapy

Purpose To establish whether maintenance lapatinib after first-line chemotherapy is beneficial in human epidermal growth factor receptor (HER) 1/HER2–positive metastatic urothelial bladder cancer (UBC). Methods Patients with metastatic UBC were screened centrally for HER1/HER2 overexpression. Patients who screened positive for HER1/2 and who did not have progressive disease during chemotherapy (four to eight cycles) were randomly assigned one to one to lapatinib or placebo after completion of first-line/initial chemotherapy for metastatic disease. The primary end point was progression-free survival (PFS). Results Between 2007 and 2013, 446 patients with UBC were screened, and 232 with HER1- or HER2-positive disease were randomly assigned. The median PFS for lapatinib and placebo was 4.5 (95% CI, 2.8 to 5.4) and 5.1 (95% CI, 3.0 to 5.8) months, respectively (hazard ratio, 1.07; 95% CI, 0.81 to 1.43; P = .63). The overall survival for lapatinib and placebo was 12.6 (95% CI, 9.0 to 16.2) and 12.0 (95% CI, 10.5 to 14.9) months, respectively (hazard ratio, 0.96; 95% CI, 0.70 to 1.31; P = .80). Discontinuation due to adverse events were similar in both arms (6% lapatinib and 5% placebo). The rate of grade 3 to 4 adverse events for lapatinib and placebo was 8.6% versus 8.1% ( P = .82). Preplanned subset analysis of patients strongly positive for HER1/HER2 (3+ on immunohistochemistry; n = 111), patients positive for only HER1 (n = 102), and patients positive for only HER2 (n = 42) showed no significant benefit with lapatinib in terms of PFS and overall survival ( P > .05 for each). Conclusion This trial did not find significant improvements in outcome by the addition of maintenance lapatinib to standard of care.

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