Severe hypovitaminosis D in metastatic gastric cancer patients from the Northern and Southern hemispheres: Data from the EXPAND phase III trial

Abstract

BACKGROUND Our primary goal was to evaluate the association between vitamin D (25-OHD) plasma levels and overall survival (OS) in metastatic gastric cancer patients receiving first-line chemotherapy in the international phase III EXPAND study (EudraCT 2007-004219-75). Here we report on 25-OHD plasma levels and OS according to geographic hemisphere of residence. METHODS 25-OHD pre-therapeutic plasma levels were measured in 630 patients using chemiluminescent immunoassay (Abbott Laboratories, Illinois). All patients were treated with chemotherapy based on capecitabine and cisplatin ± cetuximab. The Cox proportional hazard regression model was used to analyse the association between 25-OHD and survival in both treatment arms. RESULTS 549 and 73 patients were recruited in the Northern and Southern hemispheres, respectively. The majority had severe hypovitaminosis D at baseline prior to start of treatment. Only 9.2% of patients had a normal 25-OHD plasma levels (applying accepted criteria of 25-OHD insufficiency with plasma levels < 75 nmol/l; deficiency defined as < 50 nmol/l). Median 25-OHD plasma level was 38.2 nmol/l (IQR 25.8; 58.9) and mean was 43.5 nmol/l. Patients from the Southern versus Northern hemisphere had slightly higher 25-OHD levels (median 45.6 vs. 37.4 nmol/l; p = 0.0172; mean 48.92 vs. 42.74; p = 0.03 ). This difference persists when adjusting for season in a linear regression model. As expected, we observed the highest levels of 25-OHD in samples drawn during the summer season and the lowest values in winter. No proof for a negative impact of hypovitaminosis D on survival or treatment response was detected and no difference in OS was seen between patients from the Southern vs. Northern hemisphere (median 8.3 months [95%CI 7.4-10.6] vs. 10.5 [95%CI 9.4-11.3]; Hazard Ratio = 1.195; p = 0.2001). CONCLUSIONS No prognostic value of vitamin D deficiency was found in the EXPAND cohort. However, the majority of patients with metastatic gastric cancer have a severe vitamin D deficiency with only minor differences comparing Southern versus Northern hemisphere of residency. LEGAL ENTITY RESPONSIBLE FOR THE STUDY Masaryk Memorial Cancer Institute. FUNDING Masaryk Memorial Cancer Institute, University Leipzig. DISCLOSURE R. Obermannova: Advisory / Consultancy, Speaker Bureau / Expert testimony: Servier; Advisory / Consultancy, Research grant / Funding (self): Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly. F. Lordick: Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen, AstraZeneca, Astellas, Biontech, BMS, Eli Lilly, Elsevier, Excerpta Medica, Imedex, Infomedica, Iomedico AG, Medscape, MedUpdate GmbH, Merck Sharp Dohme, Merck Serono, Oncovis Gmbh, Promedicis, Springer Nature Group, StreamedUp!, Zymeworks; Research grant / Funding (institution): BMS. All other authors have declared no conflicts of interest.