Abstract PD6-02: A randomized, controlled trial of high dose vs. standard dose vitamin D for aromatase inhibitor-induced arthralgia in breast cancer survivors
Authors: Niravath P , Wang T , Hilsenbeck SG , Lipscomb K , Pavlick A , Jiralerspong S , Nangia J , Ellis M , Ademuyiwa F , Cherian M , Frith A , Ma C , Park H , Rigden C , Suresh R , Osborne CK , Rimawi MF 
Published: May 2019

Abstract
Background: Approximately half of women on aromatase inihbitor (AI) therapy develop AI-induced arthralgia (AIA), and many discontinue the medication because of this common side effect. While Vitamin D has been studied as a treatment for AIA, trial results have been conflicting thus far.
Patients and Methods: All subjects were post menopausal women who were beginning adjuvant AI therapy for stage I-III hormone receptor positive breast cancer. Patients were randomized 1:1 to receive standard dose vitamin D3 (800 IU daily for 52 weeks) or high dose vitamin D3 (50,000 IU weekly for 12 weeks, followed by 2000 IU daily for 40 weeks). All patients also took oral calcium 600 mg daily. The primary endpoint was development of AIA, as defined by pre-specified changes in the Health Assessment Questionnaire II (HAQ-II). Secondary endpoints include compliance with AI therapy, and correlation between grip strength and development of AIA. Exploratory endpoint was measurement of inflammatory cytokine reduction in each arm. The trial was designed to enroll 184 patients, but this futility analysis was performed after 93 patients were enrolled. The futility boundary for stopping the trial early was calculated as p = 0.47.
Results: All 93 patients (46 in the high dose arm, and 47 in the standard dose arm) enrolled in the study at the time of the interim analysis were evaluable. The HAQ-II was completed at 12 weeks in 76% on the high dose arm, and 68% in the standard dose arm. Subjects who did not complete the questionnaire were deemed as study failures (i.e. development of AIA was assumed). In the high dose arm, 25 patients (54%) developed AIA, compared to 27 patients (57%) in the standard dose arm. The one-tailed p value is 0.3818, and the Z-score is 0.3, yielding only a 38% conditional power that that study would find a significant difference between the two arms. Thus, the study was terminated early for futility. There was no significant difference between the two arms in adherence to AI therapy. The grip strength and inflammatory cytokine data are pending at this time. They will be ready by the time of the conference.
Conclusions: There was no significant signal for benefit of high dose vitamin D supplementation, as compared to standard dose vitamin D, for AIA prevention in post menopausal women taking adjuvant AI therapy. These results further characterize the role of Vitamin D in AIA, and they inform future clinical trials in this arena. Further research is necessary, as this remains an important cause of non-adherence to this highly effective therapy.
Citation Format: Niravath P, Wang T, Hilsenbeck SG, Lipscomb K, Pavlick A, Jiralerspong S, Nangia J, Ellis M, Ademuyiwa F, Cherian M, Frith A, Ma C, Park H, Rigden C, Suresh R, Osborne CK, Rimawi MF. A randomized, controlled trial of high dose vs. standard dose vitamin D for aromatase inhibitor-induced arthralgia in breast cancer survivors [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD6-02.