High-Dose Vitamin D Misses Cancer Trial Goal
In the 455-patient SOLARIS phase 3 trial, adding high-dose vitamin D3 to first-line chemotherapy and bevacizumab did not significantly improve progression-free survival in metastatic colorectal cancer.
The 60-second version
In SOLARIS, high-dose vitamin D3 added to chemotherapy plus bevacizumab did not significantly improve progression-free survival in previously untreated metastatic colorectal cancer.
Key points
- The double-blind phase 3 trial randomized 455 patients and is registered as NCT04094688.
- Median PFS was 11.8 versus 10.3 months, but the prespecified one-sided test was not significant at P=.25.
- Objective response and overall survival were also not significantly different.
- Common severe adverse events were similar, but this does not justify unsupervised high-dose use.
Verdict. Do not add high-dose vitamin D expecting a cancer-control benefit from this regimen; deficiency and supplement decisions remain clinical care.
ResultThe primary endpoint was negative
The phase 3 SOLARIS trial randomized 455 patients with previously untreated metastatic colorectal cancer. Adding high-dose vitamin D3 to first-line chemotherapy plus bevacizumab did not significantly improve progression-free survival compared with standard-dose vitamin D3.
The numerical median was longer in the high-dose group, but that alone does not establish benefit. The prespecified statistical test did not reject the trial's null hypothesis.
DesignWhat the two groups received
| Population | Previously untreated metastatic colorectal cancer; median age 59; 40% women. |
|---|---|
| Cancer treatment | mFOLFOX6 or FOLFIRI plus bevacizumab every two weeks in both groups. |
| High-dose arm | Vitamin D3 8,000 IU daily for 14 days, then 4,000 IU daily. |
| Comparator | Vitamin D3 400 IU daily. |
| Primary outcome | Progression-free survival by an unstratified log-rank test. |
The registered study, NCT04094688, was double-blind, randomized and phase 3. The Alliance for Clinical Trials in Oncology sponsored it with the National Cancer Institute as collaborator.
Secondary outcomesResponse and survival also showed no clear gain
| Objective response | 51% with high dose versus 44% with standard dose; P=.12. |
|---|---|
| Overall survival | Median 25.6 versus 27.0 months; P=.66. |
| Follow-up | Median 20 months at the reported analysis. |
None of these comparisons was statistically significant. The result therefore does not establish better response, delayed progression or longer survival from the high-dose add-on.
SafetyNo major difference in severe toxicity
Common grade 3 or worse events were similar: neutropenia occurred in 32% versus 30%, and hypertension in 20% versus 23%, for high versus standard dose. The authors found no clinically meaningful difference in common severe events or vitamin D-associated toxicities.
BoundaryWhat the trial does not answer
- It compared high dose with standard dose, not vitamin D with no vitamin D.
- It studied a specific first-line metastatic-disease regimen; other stages and treatment combinations were not tested.
- It does not overturn ordinary clinical care for a documented vitamin D deficiency.
- It does not justify replacing chemotherapy, bevacizumab or other proven treatment with supplements.
TakeawayHow to use the evidence
SOLARIS does not support adding high-dose vitamin D3 with the expectation of prolonging progression-free survival in this setting. Supplement use and deficiency treatment should be discussed with the oncology team.
A promising phase 2 signal was tested in phase 3 and did not hold up on the primary endpoint.