A prospective study of serum folate levels in patients with solid tumors treated with olaparib.

2025-09-27
The oncologist 30(10)
- Jamile Shammo
- Laura Owczarzak
- Nicole K Yun
- Lois Winkelman
- Sanjib Basu
- Ruta Rao
- Amina Ahmed
- Summer Dewdney
- Melody Cobleigh
- Lydia Usha

PubMed: 41014151
DOI: 10.1093/oncolo/oyaf321

Study Design

Type: Randomized Controlled Trial (RCT)
Population: patients with solid tumors treated with olaparib
Methods: open-label prospective trial, patients who developed grade 1 anemia concomitantly with folate deficiency were randomized to receive placebo or folic acid
Blinding: Open-label
Funding: Unclear

Background

Olaparib is a polyadenosine 5'-disphosphoribose polymerase inhibitor approved to treat advanced ovarian cancers with germline mutations. The link between olaparib-induced anemia and folate deficiency was described in a retrospective case series in which 87.5% of patients developed concomitant folate deficiency and anemia. We sought to prospectively evaluate this association.

Patients and methods

This is an open-label prospective trial of patients with solid tumors treated with olaparib to determine the frequency and timing of folate deficiency anemia. Patients who developed grade 1 anemia (Hgb < 12.0 g/dL) concomitantly with folate deficiency (serum folate < 7.0 ng/mL) were randomized to receive placebo or folic acid. Secondary endpoints included the impact of folic acid supplementation on serum folate and hemoglobin, transfusion needs, and need for olaparib treatment interruption, dose reduction, or drug discontinuation.

Results

Nine subjects were enrolled, with ovarian or breast cancer. Two patients were randomized to forgo folate supplementation, two were randomized to receive folate, and the rest were not randomized per protocol. Three withdrew due to disease progression. All patients demonstrated decreased folate levels after initiation of olaparib, eight occurring within 3 months. Seven patients developed a concomitant grade 1 anemia. Folate deficiency did not correlate with clinically significant anemia.

Conclusions

This trial demonstrated folate deficiency in nearly all patients starting olaparib within weeks but, deficiencies did not result in a clinically significant anemia. Folate levels normalized with supplementation and improved with olaparib discontinuation. This data warrant checking serum folate in patients receiving olaparib who develop anemia and replacing folate if deficiency is found.

Research Insights

Vitamin B9→Increased Hemoglobin Levels
Folate deficiency did not correlate with clinically significant anemia
Effect
Neutral
Effect size
Small
Vitamin B9→Normalized Folate Level
Folate levels normalized with supplementation
Effect
Beneficial
Effect size
Small

Adverse Events Reported

Vitamin B9→anemia
Seven patients developed a concomitant grade 1 anemia. Folate deficiency did not correlate with clinically significant anemia.
Finding
Reported
Grade
mild
Vitamin B9→folate deficiency
All patients demonstrated decreased folate levels after initiation of olaparib, eight occurring within 3 months.
Finding
Reported