Real-world efficacy and safety of burosumab in tumor-induced osteomalacia: case series from an early access program

Abstract

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome due to a phosphaturic tumor, which overproduces FGF23, causing hyperphosphaturia, hypophosphatemia, low 1,25(OH)2D, and osteomalacia. Complete surgical resection is the standard of care, but some tumors cannot be found, and others cannot be removed. In such difficult situations, burosumab, a fully human monoclonal antibody that targets and inhibits excess circulating FGF23, is a treatment option. Early access program (EAP) to burosumab has been established for patients with TIO in France in July 2022. Before that, access to burosumab at no cost on compassionate grounds was provided for a few patients. Between July 21, 2022 and December 3, 2023, an EAP was initiated for burosumab across 10 University Hospital Centers. The program included 9 patients (3 pre-exposed and 6 burosumab-naïve patients). The EAP included assessments of phosphatemia, pain levels using the visual analogue scale, and quality of life using the Routine Assessment of Patient Index Data 3 questionnaire. Patients' ages ranged from 33 to 62 yr, with various BMI categories. Seven patients had at least 1 follow-up visit (3 pre-exposed and 4 burosumab-naïve patients). In the burosumab-naïve group, phosphatemia levels improved in 2 patients, with 1 achieving levels >0.8 mmol/L. Pain reduction was reported in all 4 naïve patients with follow-up, while pain levels in pre-exposed patients remained stable or fluctuated. Quality of life scores indicated minimal impairment or remission in 6 patients at baseline. No serious adverse events were observed. These preliminary findings following burosumab EAP for patients with TIO in France support benefits in terms of efficacy, safety, and ease of treatment. Burosumab appears to be a promising option for patients who are ineligible or refractory to surgery.

Keywords: Fibroblast Growth Factor 23; Tumor-induced osteomalacia; burosumab; hypophosphatemia; phosphaturic tumor.

Figure 1

Early access program timeline.

Figure 2

Burosumab treatment dosage during patient follow-up in (A) burosumab-naive patients and (B) pre-exposed patients. Patient 2 and patient 6 had an initial dosage value of 0.3, but no follow-up data regarding their dosage were available.

Figure 3

Pain evolution in (A) burosumab-naive and (B) pre-exposed patients. Abbreviation: VAS, visual analog scale. Patient 2 and patient 6 had an initial pain score of 30 and 40, respectively, but no follow-up data regarding their pain score was available.

Figure 4

Serum phosphate levels in (A) burosumab-naive and (B) pre-exposed patients. The dotted lines indicate the phophatemia normal range (between 0.8 and 1.5 mmol/L.

Figure 5

Patient quality of life, using the RAPID-3 questionnaire, in (A) burosumab-naive and (B) pre-exposed patients. The RAPID-3 weighted score ranges from 0 to 10; the lower the score, the better the quality of life. Patient 2 and patient 6 had a RAPID-3 score recorded at initiation but no data available throughout the follow-up period, while patient 7 had no data recorded at any point. Abbreviation: RAPID-3, Routine Assessment of Patient Index Data 3.