Addition of High-Dose Vitamin D3 to Standard Treatment in Patients with Metastatic Colorectal Cancer: The SOLARIS Randomized Clinical Trial (Alliance A021703)
TL;DR
High-dose vitamin D3 added to standard treatment improved progression-free survival (PFS) compared to standard-dose vitamin D3 in patients with metastatic colorectal cancer (mCRC) in a phase 2 randomized clinical trial.
Abstract
Importance: In a phase 2 randomized clinical trial, high-dose vitamin D3 added to standard treatment improved progression-free survival (PFS) compared to standard-dose vitamin D3 in patients with metastatic colorectal cancer (mCRC). Objective: To determine if high-dose vitamin D3 added to standard chemotherapy improves outcomes in patients with previously untreated mCRC. Design, Setting, and Participants: Double-blind phase 3 randomized clinical trial of 455 patients with previously untreated mCRC conducted in the U.S. through the National Clinical Trials Network from October 2019 to December 2022 (database freeze: July 15, 2024). Interventions: mFOLFOX6 or FOLFIRI plus bevacizumab every 2 weeks with either high-dose vitamin D3 (8,000 IU daily x 14 days as loading dose followed by 4,000 IU daily) or standard-dose vitamin D3 (400 IU daily) until disease progression, intolerable toxicity, or withdrawal of consent. Main Outcome and Measures: The primary end point was PFS assessed by the unstratified log-rank test. Secondary end points included objective response rate (ORR), overall survival (OS), and toxicity. Prespecified subgroup analyses of PFS were performed according to known prognostic factors. Results: Among 455 randomized patients (median age, 59 years; 181 [40%] female) with median follow-up 20 months, the median PFS for high-dose vitamin D3 (n=228) was 11.8 months (95% CI, 10.3-13.3) vs 10.3 months (95% CI, 9.4-12.2) for standard-dose vitamin D3 (n=227), one-sided log-rank P = .25. There were no significant differences in ORR between high-dose and standard-dose vitamin D3 (51% [95% CI, 44-58%] vs 44% [95% CI, 37-50%], respectively; P = .12), nor in OS (median, 25.6 vs 27.0 months; one-sided log-rank P = .66). There were no clinically meaningful differences in the most common grade ≥3 adverse events between high- and standard-dose arms, including neutropenia (n=67 [32%] vs n=62 [30%]) and hypertension (n=42 [20%] vs n=49 [23%]), nor in incidence of vitamin D-associated toxicities. Conclusions and Relevance: Among patients with previously untreated mCRC, addition of high-dose vitamin D3, vs standard-dose vitamin D3, to standard chemotherapy plus bevacizumab did not improve PFS.