No benefit of high-dose vitamin D3 supplementation in mCRC

A high dose (4,000 IU/day) of vitamin D₃ did not improve survival in patients with metastatic colorectal cancer (mCRC) who were treated with standard chemotherapy, according to the results of the phase 3 SOLARIS trial.

Vitamin D has demonstrated anti-cancer activity in pre-clinical studies [1]. In addition, epidemiologic cohort studies have shown a significant association between higher plasma 25-hydroxy vitamin D levels and improved survival among patients with colorectal cancer [2]. Previously, the phase 2 SUNSHINE study showed an improvement in progression-free survival (PFS) for patients with mCRC on high-dose vitamin D₃ compared with a standard dose (HR 0.64) [3]. This was further evaluated in the double-blind, phase 3 SOLARIS trial (NCT04094688) [4]. Dr Kimmie Ng (Dana-Farber Cancer Institute, MA, USA) presented the results.

SOLARIS randomised 455 previously untreated participants with mCRC 1:1 to receive FOLFOX or FOLFIRI plus bevacizumab with high-dose vitamin D₃ (8,000 IU/day for 2 weeks, followed by 4,000 IU/day) or with standard-dose vitamin D₃ (400 IU/day). The primary endpoint was PFS.

After a median follow-up of 20 months, no benefit of high-dose vitamin D₃ was observed. The median PFS was 11.8 months in the high-dose arm versus 10.3 months in the standard-dose arm (HR 0.92; 95% CI 0.73–1.16; P=0.25). A lack of benefit was observed in all prespecified subgroups, except for participants with a left-sided tumour (HR 0.74; 95% CI 0.55–1.00) versus those with a right-sided tumour (HR 1.35; 95% CI 0.93–1.97; P_interaction=0.015). “In the SUNSHINE trial, we observed this finding as well,” Dr Ng remarked. “This is hypothesis-generating and requires further study and confirmation.” High-dose vitamin D₃ did not influence any adverse events of chemotherapy.

1. Pereira F, et al. FEBS J. 2024;291:2485-2518.
2. Wang QL, et al. Clin Cancer Res. 2023;29:2621-2630.
3. Ng K, et al. JAMA. 2019;321:1370-1379.
4. Ng K, et al. SOLARIS (Alliance A021703): A multicenter double-blind phase III randomized clinical trial (RCT) of vitamin D (VitD) combined with standard chemotherapy plus bevacizumab (bev) in patients (pts) with previously untreated metastatic colorectal cancer (mCRC). Abstract LBA26, ESMO Congress 2024, 13–17 September, Barcelona, Spain.

 

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Posted on 4 November 20244 November 2024