Optimizing Outcomes: Bevacizumab with Carboplatin and Paclitaxel in 5110 Ovarian Cancer Patients—A Systematic Review and Meta-Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Data Sources and Search Strategy
2.2. Study Selection and Data Extraction
2.3. Assessment of Bias Risk and Evidence
2.4. Statistical Analysis
3. Results
3.1. Study Search and Selection
3.2. Study Characteristics
3.3. Efficacy Outcomes
3.4. Safety Outcomes
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Component | Definition |
---|---|
P (patients) | Patients with ovarian cancer |
I (intervention) | Combination therapy of carboplatin, paclitaxel, and bevacizumab |
C (comparator) | Combination therapy of carboplatin and paclitaxel |
O (outcomes) | Efficacy: OS and PFS; safety (adverse events): hypertension, heart failure, CNS bleeding, non-CNS bleeding, thromboembolic events (any, arterial, or venous), neutropenia, febrile neutropenia, anemia, wound complications, GI disorders, GI perforation, pain, dermatologic disorders, and proteinuria |
S (study design) | RCTs |
Study Name | Study Period | Country | Study Design | Patient Population | Intervention | Comparator | OS Outcome | PFS Outcome | Safety Outcomes |
---|---|---|---|---|---|---|---|---|---|
Coleman 2017 [24]/GOG-0213 study | December 2007–November 2014 | United States, Japan, and South Korea | Multi-center, open-label, randomized phase 3 trial | Adult females (aged ≥ 18 years) with recurrent measurable or evaluable epithelial ovarian, primary peritoneal, or fallopian tube cancer (n = 674) | Standard chemotherapy regimen plus bevacizumab (15 mg/kg) every 3 weeks, which was then continued as maintenance every 3 weeks until disease progression or unacceptable toxicity | Standard chemotherapy (six 3-weekly cycles of paclitaxel [175 mg/m2] and carboplatin [AUC 5]) | HR: 0.829 [0.683–1.005], p = 0.056 | HR: 0.628 [0.534–0.739], p < 0.0001 | Hypertension, heart failure, CNS bleeding, non-CNS bleeding, arterial thromboembolic events, venous thromboembolic events, neutropenia, wound complications, GI disorders, GI perforation, pain, dermatologic disorders, and proteinuria |
Gore 2019 [25]/GOG-0241 study | March 2010–August 2013 | United Kingdom and the United States | Multi-center phase 3 factorial trial | Patients with histological diagnosis of primary mEOC; aged ≥ 18 years; newly diagnosed FIGO stage II–IV, or recurrence after stage I disease; no previous chemotherapy; ECOG performance status 0–2 (n = 24) | Carboplatin, paclitaxel, and bevacizumab (15 mg/kg intravenous every 3 weeks); then, bevacizumab maintenance (15 mg/kg on day 1, every 3 weeks) | Carboplatin (AUC 5/6) and paclitaxel (175 mg/m2), both intravenous, day 1 | HR: 1.47, p = 0.44 | HR: 1.12, p = 0.82 | Hypertension, CNS bleeding, non-CNS bleeding, any thromboembolic events, neutropenia, anemia, GI perforation, and pain |
Oza 2015 [26]/ICON7 study | April 2006–March 2013 | 11 countries across Europe, Canada, Australia, and New Zealand | International, phase 3, open-label, randomized trial | Patients aged ≥ 18 years; with newly diagnosed epithelial ovarian, fallopian tube, or primary peritoneal cancer; an ECOG performance status of 0–2; FIGO stage IIb–IV or high-risk (grade 3 or clear cell histology) stage I–IIa disease (n = 1528) | Standard chemotherapy plus intravenous bevacizumab 7.5 mg/kg every 3 weeks given concurrently and continued with up to 12 further 3-weekly cycles of maintenance therapy | Standard chemotherapy (six 3-weekly cycles of intravenous carboplatin [AUC 5 or 6] and paclitaxel 175 mg/m2) | HR: 0.99 [0.85–1.14], p = 0.85 | HR: 0.93 [0.83–1.05], p = 0.25 | Not available |
Perren 2011 [27]/ICON7 study | April 2006–February 2010 | United Kingdom, Germany, France, Canada, Australia, New Zealand, Denmark, Finland, Norway, Sweden, and Spain | Phase 3, open-label, randomized trial | Females with histologically confirmed, high-risk, early-stage disease (FIGO stage I or IIA and clear-cell or grade 3 tumors) or advanced (FIGO stage IIB to IV) epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer (n = 1498) | Standard-chemotherapy group plus bevacizumab (7.5 mg/kg) given concurrently every 3 weeks for 5 or 6 cycles and continued for 12 additional cycles or until disease progression | Carboplatin (AUC 5 or 6) and paclitaxel (175 mg/m2) given every 3 weeks for 6 cycles (standard-chemotherapy group) | Not available | Not available | Hypertension, heart failure, CNS bleeding, any thromboembolic events, arterial thromboembolic events, venous thromboembolic events, neutropenia, febrile neutropenia, wound complications, GI perforation, and proteinuria |
Pignata 2021 [28]/NCT01802749 study | December 2013–February 2018 | France, Greece, Italy, Monaco, and Switzerland | Academic, multi-center, open-label, randomized phase 3 trial | Females aged ≥ 18 years with histologically confirmed FIGO stage IIIB–IV ovarian cancer, fallopian tube carcinoma, or peritoneal carcinoma (including mixed Mullerian tumors) (n = 43) | Carboplatin-based doublet plus bevacizumab | Intravenous carboplatin-based doublet (carboplatin AUC 5 on day 1 plus paclitaxel 175 mg/m2 on day 1, every 21 days | Not available | HR: 0.34 [0.15–0.80] | Not available |
Rouizer 2017 [29]/ANTHALYA study | January 2013–August 2016 | France | Multi-center, open-label, non-comparative phase 2 study | Females aged ≥ 18 years with histologically confirmed, chemotherapy-naive, high-risk FIGO stage IIIC/IV epithelial ovarian carcinoma, fallopian tube carcinoma, or primary peritoneal carcinoma (ineligible for primary complete debulking surgery) (n = 95) | Four cycles of neoadjuvant carboplatin-paclitaxel + 3 concomitant cycles of bevacizumab 15 mg/kg | Four cycles of neoadjuvant carboplatin-paclitaxel | Not available | Not available | GI disorders |
Tewari 2019 [30]/GOG-0218 study | October 2005–January 2018 | United States, Canada, Japan, and South Korea | International, multi-center, double-blind, placebo-controlled, phase 3 trial | Females with stage III or IV epithelial ovarian, primary peritoneal, or fallopian tube carcinoma (n = 1248) | Six 21-day cycles of intravenous carboplatin (AUC 6) plus paclitaxel (175 mg/m2), followed by bevacizumab (15 mg/kg) in cycles 7 to 22 | Six 21-day cycles of intravenous carboplatin (AUC 6) plus paclitaxel (175 mg/m2), followed by 16 21-day cycles of placebo | HR: 0.96 [0.85–1.09], p = 0.53 | HR: 0.717 [0.625–0.824], p < 0.001 | Hypertension, CNS bleeding, non-CNS bleeding, arterial thromboembolic events, venous thromboembolic events, neutropenia, febrile neutropenia, wound complications, GI disorders, pain, and proteinuria |
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Kim, Y.J.; Lee, H.M.; Lee, G.E.; Yoo, J.H.; Lee, H.J.; Rhie, S.J. Optimizing Outcomes: Bevacizumab with Carboplatin and Paclitaxel in 5110 Ovarian Cancer Patients—A Systematic Review and Meta-Analysis. Pharmaceuticals 2024, 17, 1095. https://doi.org/10.3390/ph17081095
Kim YJ, Lee HM, Lee GE, Yoo JH, Lee HJ, Rhie SJ. Optimizing Outcomes: Bevacizumab with Carboplatin and Paclitaxel in 5110 Ovarian Cancer Patients—A Systematic Review and Meta-Analysis. Pharmaceuticals. 2024; 17(8):1095. https://doi.org/10.3390/ph17081095
Chicago/Turabian StyleKim, Yu Jin, Hee Min Lee, Ga Eun Lee, Jin Hui Yoo, Hwa Jeong Lee, and Sandy Jeong Rhie. 2024. "Optimizing Outcomes: Bevacizumab with Carboplatin and Paclitaxel in 5110 Ovarian Cancer Patients—A Systematic Review and Meta-Analysis" Pharmaceuticals 17, no. 8: 1095. https://doi.org/10.3390/ph17081095
APA StyleKim, Y. J., Lee, H. M., Lee, G. E., Yoo, J. H., Lee, H. J., & Rhie, S. J. (2024). Optimizing Outcomes: Bevacizumab with Carboplatin and Paclitaxel in 5110 Ovarian Cancer Patients—A Systematic Review and Meta-Analysis. Pharmaceuticals, 17(8), 1095. https://doi.org/10.3390/ph17081095