Search

Background: Older patients with ovarian cancer represent a heterogeneous population. The French National Group of Investigators for the Study of Ovarian and Breast Cancer developed the geriatric vulnerability score (GVS) to identify geriatric parameters predictive of poor outcomes. A prospective validation of the GVS was needed., Methods: The EWOC-1 study (NCT02001272) was an international, open-label, phase 2, three-arm trial designed according to a two-step process. Patients aged 70 years or older with newly diagnosed stage III or IV ovarian cancer were identified and the GVS determined. Those with a GVS of 3 or greater were randomly assigned to the EWOC-1 trial, stratified by country and surgical outcome, to receive three different carboplatin with or without paclitaxel regimens; those not included in the EWOC-1 trial were followed up in the EWOC-1 registry. External validation of the GVS was a secondary endpoint of the trial. Three validation cohorts were identified: the total population (validation cohort 1 [V1], n=447), the registry-only population (validation cohort 2 [V2], n=327), and the carboplatin-paclitaxel-treated population (validation cohort 3 [V3], n=320)., Findings: From Dec 11, 2013, to Nov 16, 2018, 447 patients were included in 48 academic centres in six countries; 120 in the EWOC-1 trial and 327 in the EWOC-1 registry. Median follow-up was 19·7 (95% CI 8·5-29·7) months for the total cohort; missing values were low (<2%). According to the maximum likelihood analysis, the hazard ratio (HR) of death in V1 was 1·8 (95% CI 1·1-3·1, p=0·029) for those with a GVS of 1; 2·4 (1·4-4·0, p=0·0009) with a GVS of 2; 4·1 (2·5-7·0, p<0·0001) for a GVS of 3; 5·5 (3·3-9·3, p<0·0001) for a GVS of 4; and 9·1 (4·7-17·5, p<0·0001) for a GVS of 5 compared with a score of 0. Whatever the validation cohort, GVS of 3 or more significantly segregated two groups with different overall survival: V1 (median 13·2 [95% CI: 10·8-18·7] vs 40·8 [32·0-45·6] months; HR 2·8 [95% CI 2·2-3·7]; p<0·0001); V2 (11·9 [95% CI 8·8-18·1] vs 40·8 [32·0-45·6] months, HR 3·5 [2·5-4·9]; p<0·0001); and V3 (18·1 [95% CI 15·8-31·8] vs 43·0 [40·6-49·7] months, HR 2·6 [1·9 to 3·7]; p<0·0001)., Interpretation: The GVS has high prognostic performance for overall survival in patients with advanced ovarian cancer, independently of geographic and historic effect (V1), as well as treatment patterns (V3), validated in an international population. Even though the GVS is time consuming it will allow the stratification of populations for clinical research and might permit the orientation of the geriatric intervention to specific domains., Funding: French National Cancer Institute., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests CF reports a grant from the French National Cancer Institute during the conduct of the study; personal fees from Leo Pharma, Pfizer, MSD Oncology, Teva, AstraZeneca, Baxter, Eisai, Janssen Oncology, Novartis, Chugai Pharma, and Astellas Pharma, outside the submitted work; grants from Chugai Pharma, Pfizer, Pierre Fabre, and Astellas Pharma, outside the submitted work; and non-financial support from Janssen Oncology, Pierre Fabre, AstraZeneca, and Leo Pharma, outside the submitted work. FT reports grants from French National Institute (via Hospices Civils de Lyon), during the conduct of the study. DL reports grants from PharmaMar, Merck Serono, Novartis, AstraZeneca, Clovis Oncology, Tesaro, GSK, Roche, Genmab, and Immunogen, during the conduct of the study. AF reports personal fees from MSD, AstraZeneca, GSK, and Clovis Oncology, outside the submitted work. FR reports participation in a specialist advisory board for Bristol Myers Squibb. OT reports grants and personal fees from Roche and MSD, grants from BMS, and personal fees from Novartis-Sandoz, Pfizer, Lilly, AstraZeneca, Daiichi Sankyo, Eisai, Pierre Fabre, and Seagen, outside the submitted work. EP-L reports personal fees and non-financial support from AstraZeneca, Tesaro, and Roche; personal fees from Clovis, Incyte, and Pfizer; and other from Association de Recherche sur les CAncers dont GYnécologiques (ARCAGY) Research, outside the submitted work. All other authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)