Denosumab in advanced/unresectable giant-cell tumour of bone (GCTB): For how long?
Giant-cell tumours of bone (GCTB) are RANK/RANK-ligand (RANKL) positive, aggressive and progressive osteolytic tumours. Denosumab, a RANKL inhibitor, was FDA-approved for adults and skeletally mature adolescents with unresectable GCTB or when surgical resection is likely to result in severe morbidity. Data on long-term toxicity and activity of denosumab monthly 'GCTB-schedule' (120 mg per 12/year, 1440 mg total dose/year) are lacking.



Patients with GCTB receiving denosumab, 120 mg on days 1, 8, 15, 29 and every 4 weeks thereafter, from 2006 to 2015 treated in two centres were included. Long-term toxicity was evaluated.



Ninety-seven patients were identified. 43 patients underwent resection of the tumour with a median time on denosumab treatment of 12 months (range 6-45 months). Fifty-four patients had unresectable GCTB's (male/female 23/31, median age 35 years [range: 13-76 years], 26% presented with lung metastases, 31% had primary tumor located to the spine, 63% were relapsed after previous surgery) with a median time on denosumab of 54 months (9-115 months). In the unresectable GCTB group, tumour control and clinical benefits were observed in all patients undergoing denosumab, whereas 40% of patients discontinuing denosumab had tumour progression after a median of 8 months (range 7-15 months).



Overall, six (6%) patients developed osteonecrosis of jaw (ONJ): 1/43 (2%) in the resectable group, 5/54 (9%) in the unresectable group, with a 5-year ONJ-free survival of 92% (95% CI 84-100). Only patients with prolonged treatment experienced mild peripheral neuropathy (6/54, 11%), skin rash (5/54, 9%), hypophosphataemia (2/54, 4%) and atypical femoral fracture (2/54, 4%).



Prolonged treatment with denosumab has sustained activity in GCTB, with a mild toxicity profile. The dose-dependent toxicity observed recommends a careful and strict monitoring of patients who need prolonged treatment. Decreased dose-intensity schedules should be further explored in unresectable GCTB.
Istituto Ortopedico Rizzoli, Bologna, Italy. Electronic address: emanuela.palmerini@ior.it.
E
E
Palmerini
Sarcoma Oncology Center, Santa Monica, CA, USA.
N S
NS
Chawla
Istituto Ortopedico Rizzoli, Bologna, Italy.
S
S
Ferrari
Sarcoma Oncology Center, Santa Monica, CA, USA.
M
M
Sudan
Istituto Ortopedico Rizzoli, Bologna, Italy.
P
P
Picci
Istituto Ortopedico Rizzoli, Bologna, Italy.
E
E
Marchesi
Istituto Ortopedico Rizzoli, Bologna, Italy.
M Piccinni
MP
Leopardi
Sarcoma Oncology Center, Santa Monica, CA, USA.
I
I
Syed
Sarcoma Oncology Center, Santa Monica, CA, USA.
K K
KK
Sankhala
Sarcoma Oncology Center, Santa Monica, CA, USA.
P
P
Parthasarathy
Sarcoma Oncology Center, Santa Monica, CA, USA.
W E
WE
Mendanha
Istituto Ortopedico Rizzoli, Bologna, Italy.
M
M
Pierini
Istituto Ortopedico Rizzoli, Bologna, Italy.
A
A
Paioli
Sarcoma Oncology Center, Santa Monica, CA, USA.
S P
SP
Chawla
D000293:Adolescent; D000328:Adult; D000368:Aged; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000453:epidemiology / Q000209:etiology; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D000069448:Denosumab / Q000008:administration & dosage*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005266:Femoral Neoplasms / Q000188:drug therapy / Q000473:pathology; D018212:Giant Cell Tumor of Bone / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary; D006801:Humans; D007512:Ischium; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D011884:Radius / Q000000981:diagnostic imaging; D012189:Retrospective Studies; D012447:Sacrum; D012888:Skull Neoplasms / Q000188:drug therapy / Q000473:pathology; D013125:Spinal Neoplasms / Q000188:drug therapy / Q000473:pathology; D013977:Tibia; D013997:Time Factors; D055815:Young Adult
D050071:Bone Density Conservation Agents; D000069448:Denosumab
Denosumab; GCTB; Giant-cell tumour of the bone; ONJ; Receptor activator of nuclear factor κB ligand