LBA26 - SOLARIS (Alliance A021703): A multicenter double-blind phase III randomized clinical trial (RCT) of vitamin D (VitD) combined with standard chemotherapy plus bevacizumab (bev) in patients (pts) with previously untreated metastatic colorectal cancer (mCRC)

Background

Higher 25-hydroxyvitamin D levels are associated with improved CRC survival. The SUNSHINE phase II RCT found that pts with mCRC receiving 1^st-line chemo + bev + high-dose VitD3 had improved progression-free survival (PFS) vs standard-dose VitD3. SOLARIS was designed to further evaluate the efficacy of VitD in mCRC.

Methods

SOLARIS was a double-blind phase III RCT. Eligible pts had mCRC and no prior therapy; ECOG PS 0-1; and were not taking VitD ≥2,000 IU/d. Pts received mFOLFOX6 or FOLFIRI + bev with 1:1 randomization to high-dose VitD3 (8,000 IU/d x 14d then 4,000 IU/d) vs standard-dose (400 IU/d). Stratification factors: chemo backbone, PS, tumor sidedness. Pts were treated until disease progression, unacceptable toxicity, or withdrawal of consent. The primary intent-to-treat analysis compared PFS between arms using the unstratified log-rank test. HR (95% CI) from a Cox model and median PFS (mPFS) using Kaplan-Meier method was calculated. A total of 273 PFS events from 450 pts with 1 interim analysis for futility yields 90% power to detect HR 0.70 (mPFS 10 vs 14.3 mo) using a 1-sided log-rank test with α=0.05. Secondary endpoints: response rate (RR), overall survival (OS), toxicity.

Results

455 pts were randomized 10/2019 - 12/2022. Median age 59 yrs (range 27-92), 60% male, 52% PS 0, 64% left-sided primary. Median follow-up for PFS 20 mo (Q1, Q3: 7, 35 mo) with 286 events. High-dose VitD3 did not improve PFS vs standard-dose VitD3 (mPFS 11.8 vs 10.3 mo; HR 0.92, 95% CI 0.73-1.16; log-rank P=0.25), RR was 51% vs 44% (P=0.12), and mOS was 25.6 vs 27.0 mo (HR 1.05, 95% CI 0.81-1.36; log-rank P=0.34). Pre-planned subgroup analyses show a PFS benefit in pts with left-sided mCRC treated with high- vs standard-dose VitD3 (HR 0.74, 95% CI 0.55-1.00; P interaction=0.02). The most common grade ≥3 toxicities were not different between arms, including neutropenia/leukopenia, hypertension, peripheral neuropathy, and diarrhea.

Conclusions

Addition of high-dose VitD3 to standard treatment did not improve PFS vs standard-dose VitD3 in pts with mCRC, although a potential benefit was seen in pts with left-sided mCRC.

Clinical trial identification

NCT04094688.

Editorial acknowledgement

Legal entity responsible for the study

The Alliance for Clinical Trials in Oncology cooperative group.

Funding

NIH/NCI U10CA180821, U10CA180882, Pharmavite LLC.

Disclosure

All authors have declared no conflicts of interest.