High-dose vitamin D3 (cholecalciferol) add-on fails to move the needle on PFS in 1L mCRC (SOLARIS)

Vitamin D3 (cholecalciferol) supplementation was tested as a non-oncologic add-on to standard first-line mCRC therapy—mFOLFOX6 or FOLFIRI plus bevacizumab—in the US-based, double-blind SOLARIS Phase 3 trial (NCT04094688; n=455; enrolled Oct 2019–Dec 2022; database freeze July 15, 2024). Median PFS was 11.8 months with high-dose vitamin D3 (8000 IU daily ×14-day loading, then 4000 IU daily) vs 10.3 months with standard-dose vitamin D3 (400 IU daily) (1-sided P=.25), with no significant differences in ORR (51% vs 44%; P=.12) or OS (25.6 vs 27.0 months; 1-sided P=.66); this PFS/OS range is broadly in-line with historical doublet chemo + bevacizumab benchmarks (e.g., bevacizumab + oxaliplatin-based chemo PFS ~9–10 months in older Phase 3 data), while triplet FOLFOXIRI+bevacizumab typically yields PFS ~12 months in selected fit patients. Grade ≥3 AEs were similar between arms (e.g., neutropenia 32% vs 30%; hypertension 20% vs 23%), and vitamin D–associated toxicities were not meaningfully increased.