Alliance SOLARIS Trial: Vitamin D3 Fails to Boost Colorectal Cancer Survival
High-dose vitamin D3 does not improve progression-free survival in advanced colorectal cancer

August 13 - For patients with advanced colorectal cancer, adding high-dose vitamin D3 to standard first-line treatment does not improve progression-free survival, according to the results from the Phase III SOLARIS trial (Alliance A021703) published in the Journal of the American Medical Association.

Experimental evidence has suggested that vitamin D may have antineoplastic activity, including effects on tumor cell growth, cell death, inflammation, immune responses. Earlier clinical research, including the randomized Phase II SUNSHINE trial, suggested that high doses of vitamin D3 might improve progression-free survival in patients with advanced or metastatic colorectal cancer. SOLARIS was designed to determine whether those findings could be confirmed in a larger Phase III trial. But this trial provided evidence that the benefit is not enough to be statistically significant.

Dr. Kimmie Ng“While we are disappointed that high-dose vitamin D3 did not improve overall outcomes in patients with metastatic colorectal cancer, these definitive findings provide clear guidance for oncology clinicians and patients navigating treatment decisions,” said lead author Kimmie Ng, MD, MPH, Professor of Medicine at Harvard Medical School, Associate Chief of the Division of Gastrointestinal Oncology at Dana-Farber Cancer Institute (DFCI), and the Founding Director of the Young-Onset Colorectal Cancer Center at DFCI.

Key takeaways

  • Main result: Patients who received high-dose vitamin D3 had a median progression-free survival of 11.8 months, compared with 10.3 months for those who received standard-dose vitamin D3. This difference was not statistically significant.
  • Overall survival and tumor response: Overall survival was also similar between the groups (25.6 months vs. 27.0 months), as were objective response rates (51% vs. 44%). Neither difference was statistically significant.
  • Safety and tolerability: High-dose vitamin D3 was generally well tolerated when given with standard treatment. Vitamin D-related complications, such as high blood calcium and kidney stones), were rare, with no significant difference between the treatment groups.
  • Vitamin D levels: The high-dose vitamin D3 regimen successfully increased participants' vitamin D blood levels into the target range.

About the study

SOLARIS enrolled 455 patients with previously untreated metastatic colorectal cancer at 151 academic and community cancer centers across the United States through the National Clinical Trials Network between October 2019 and December 2022. All participants received standard first-line chemotherapy (mFOLFOX6 or FOLFIRI) plus the targeted monoclonal antibody bevacizumab. They were randomly assigned to receive high-dose or standard-dose vitamin D3.

The primary endpoint was progression-free survival. Secondary endpoints included overall survival, tumor response, and safety.

What We Learned about Tumor Location

Although the overall trial did not demonstrate a benefit from high-dose vitamin D3, researchers observed a potentially important finding in a prespecified subgroup analysis based on the location of the primary tumor.

  • Left-sided tumors: Patients with left-side primary colorectal tumors had a median progression-free survival of 13.8 months with high-dose vitamin D3  compared with  10.2 months with standard-dose vitamin D3 . The subgroup analysis suggested a potential benefit.
  • Right-sided tumors: No similar benefit was observed among patients with right-sided primary tumors.

Dr. Jeffrey Meyerhardt“The signal we observed in left-sided primary tumors is intriguing and aligns with prior translational work suggesting distinct biological subtypes respond differently to pathway interventions,” noted co-author Jeffrey A. Meyerhardt, MD, MPH, Chief Clinical Research Officer at Dana-Farber Cancer Institute. “While these findings are hypothesis generating, they highlight the value of subgroup and biomarker analyses in understanding how the tumor microenvironment interacts with supportive therapies.”

The Alliance expresses its gratitude to the participants, patient advocates, investigators, and clinical teams who participated in SOLARIS. Their contributions helped answer an important question about the role of vitamin D3 in metastatic colorectal cancer and will help inform future research and clinical trials. Additional laboratory studies using patient samples collected during the trial are underway to learn more about the biology of vitamin D and colorectal cancer.

(Photo credit for Dr. Ng: Nicole Loeb)