Roberto Sorio1, Célia Roemer-Becuwe2, Felix Hilpert3, Emma Gibbs4, Yolanda García5, Janne Kaern6, Manon Huizing7, Petronella Witteveen8, Flora Zagouri9, David Coeffic10, Hans-Joachim Lück11, Antonio González-Martín12, Gunnar Kristensen13, Charles-Briac Levaché14, Chee Khoon Lee4, Val Gebski4, Eric Pujade-Lauraine15. 1. MITO and Centro di Riferimento Oncologico, CRO-IRCCS, Via F. Gallini, 2 - 33081 Aviano, PN, Italy. Electronic address: rsorio@cro.it. 2. GINECO and Centre d'Oncologie de Gentilly, 2 rue Marie Marvingt, 54000 Nancy, France. 3. AGO and Onkologisches Therapiezentrum am Krankenhaus Jerusalem Hamburg, Moorkamp 2-6, 20357 Hamburg, Germany. 4. National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Locked Bag 77, Camperdown, Sydney, NSW 1450, Australia. 5. GEICO and Hospital Universitari Parc Taulí, Parc Taulí 1, 08208 Sabadell, Barcelona, Spain. 6. NSGO and Oslo University Hospital HF, Radiumhospitalet, Postboks 4950, Nydalen, N-0424 Oslo, Norway. 7. BGOG and Universitair Ziekenhuis Antwerpen, Wilrijkstraat 10, 2650 Edegem, Belgium. 8. DGOG and University Medical Center Utrecht, F02.126, PO Box 85500, 3508 GA Utrecht, The Netherlands. 9. HECOG and Department of Clinical Therapeutics, Medical School, University of Athens, 133, Vas Sofias Av, 11528 Athens, Greece. 10. GINECO and Polyclinique Courlancy, 38 rue de Courlancy, 51100 Reims, France. 11. AGO and Gynäkologisch-Onkologische Praxis am Pelikanplatz, Pelikanplatz 23, D30177 Hannover, Germany. 12. GEICO and MD Anderson Cancer Center Spain, C/Arturo Soria 270, 28033 Madrid, Spain. 13. NSGO and Department of Gynecological Cancer and Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital and Institute for Clinical Medicine, Oslo University, Postboks 4950, Nydalen, N-0424 Oslo, Norway. 14. GINECO and Clinique Francheville, 38 Boulevard de Vésone, BP 4063, 24000 Périgueux, France. 15. GINECO and Université Paris Descartes, AP-HP, Hôpitaux Universitaires Paris Centre, Site Hôtel-Dieu - Oncologie, 1 Place du Parvis Notre-Dame - Place Jean-Paul II, 75004 Paris, France.
Abstract
BACKGROUND: The AURELIA trial demonstrated significantly improved progression-free survival (PFS) with bevacizumab added to chemotherapy for platinum-resistant ovarian cancer (PROC). METHODS:Patients with PROC were randomised to receive investigator-selected single-agent chemotherapy alone or with bevacizumab. Post-hoc exploratory analyses assessed efficacy, safety and patient-reported outcomes according to age <65 versus ≥65years. RESULTS: In the 133 patients (37%) aged ≥65years, baseline hypertension was more frequent and ascites was less common than in patients <65years. The magnitude of PFS benefit from bevacizumab was similar in patients ≥65 versus <65years (hazard ratio 0.44 [95% CI, 0.31-0.64] versus 0.49 [95% CI, 0.37-0.64], respectively, treatment-age interaction p=0.58), with similar improvements in response rates. Grade≥3 hypertension was more common with bevacizumab than chemotherapy alone in both subgroups, and more common in older than younger patients irrespective of treatment. However, there was no excess of other adverse events of specific interest for bevacizumab, including venous thromboembolic events, in older patients. More patients receiving bevacizumab in the younger but not the older subgroup showed improved gastrointestinal/abdominal symptoms. CONCLUSION: In exploratory analyses, PFS and response rate improvement with bevacizumab were consistent in older and younger patients. Grade≥3 hypertension was more common in elderly bevacizumab-treated patients; careful monitoring is recommended. Overall, bevacizumab-containing therapy was well tolerated in a selected population aged ≥65years, suggesting a favourable benefit:risk profile. However, geriatric assessments are needed to improve selection of elderly patients potentially gaining symptom and quality of life improvements from bevacizumab-containing therapy. CLINICAL TRIALS REGISTRATION: ClinicalTrials.govNCT00976911.
RCT Entities:
BACKGROUND: The AURELIA trial demonstrated significantly improved progression-free survival (PFS) with bevacizumab added to chemotherapy for platinum-resistant ovarian cancer (PROC). METHODS:Patients with PROC were randomised to receive investigator-selected single-agent chemotherapy alone or with bevacizumab. Post-hoc exploratory analyses assessed efficacy, safety and patient-reported outcomes according to age <65 versus ≥65years. RESULTS: In the 133 patients (37%) aged ≥65years, baseline hypertension was more frequent and ascites was less common than in patients <65years. The magnitude of PFS benefit from bevacizumab was similar in patients ≥65 versus <65years (hazard ratio 0.44 [95% CI, 0.31-0.64] versus 0.49 [95% CI, 0.37-0.64], respectively, treatment-age interaction p=0.58), with similar improvements in response rates. Grade≥3 hypertension was more common with bevacizumab than chemotherapy alone in both subgroups, and more common in older than younger patients irrespective of treatment. However, there was no excess of other adverse events of specific interest for bevacizumab, including venous thromboembolic events, in older patients. More patients receiving bevacizumab in the younger but not the older subgroup showed improved gastrointestinal/abdominal symptoms. CONCLUSION: In exploratory analyses, PFS and response rate improvement with bevacizumab were consistent in older and younger patients. Grade≥3 hypertension was more common in elderly bevacizumab-treated patients; careful monitoring is recommended. Overall, bevacizumab-containing therapy was well tolerated in a selected population aged ≥65years, suggesting a favourable benefit:risk profile. However, geriatric assessments are needed to improve selection of elderly patients potentially gaining symptom and quality of life improvements from bevacizumab-containing therapy. CLINICAL TRIALS REGISTRATION: ClinicalTrials.govNCT00976911.