2125P - Potential ROle of hypoVItaminosis D in patiENts with cancer treated with immune ChEckpoint inhibitors (PROVIDENCE): A prospective observational study

Background

Hypovitaminosis D can have a negative impact in patients (pts) with cancer. We hypothesized that systematic vitamin D repletion could improve outcomes in pts receiving immune-checkpoint inhibitors (ICIs).

Methods

We planned a prospective observational study (PROVIDENCE) to investigate vitamin D levels in pts with advanced cancer receiving ICIs (cohort 1 at treatment initiation, cohort 2 during treatment) and the impact of systematic repletion in the case of hypovitaminosis on survival and toxicity outcomes. In an exploratory analysis, we compared clinical outcomes of cohort 1 with a control cohort of pts followed at the participating centers who did not receive systematic vitamin D repletion.

Results

Overall, 164 pts were prospectively recruited. In cohort 1, consisting of 101 pts with 94.1% hypovitaminosis (≤30 ng/ml) at baseline, adequate repletion with cholecalciferol was obtained in 70.1% at the three months re-assessment. Cohort 2 consisted of 63 pts assessed for vitamin D at a median time of 3.7 months since immunotherapy initiation, with no pts having adequate levels (>30 ng/ml). Even in cohort 2, systematic supplementation led to adequate levels in 77.8% of pts at the three months re-assessment. Compared to a retrospective control group of 238 pts without systematic vitamin D repletion, PROVIDENCE cohort 1 showed longer OS and time to treatment failure (TTF), p=0.013 and p=0.017. The IPTW-fitted multivariable Cox regression confirmed the significantly decreased risk of death (HR 0.55, 95%CI: 0.34-0.90) and treatment discontinuation (HR 0.61, 95%CI: 0.40-0.91) for pts from PROVIDENCE cohort 1 in comparison to the control cohort. In the context of longer treatment exposure, the cumulative incidence of any grade irAEs was higher in the PROVIDENCE cohort 1 compared to the control cohort. Nevertheless, pts from cohort 1 experienced a significantly decreased risk of all grade thyroid irAEs than the control cohort (OR 0.16, 95%CI: 0.03-0.85).

Conclusions

The PROVIDENCE study suggests the potential positive impact of early systematic vitamin D supplementation on outcome of pts with advanced cancer receiving ICIs and support adequate repletion as a possible prophylaxis for thyroid irAEs.

Clinical trial identification

Not Applicable

Editorial acknowledgement

Not applicable

Legal entity responsible for the study

University Hospital of Parma.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.