Abstract
Purpose: After standard multimodal therapy, the prognosis of relapsed and unresectable high-grade osteosarcoma is dismal and unchanged over the last decades. Recently, mitogen-activated protein kinases were shown to be activated in osteosarcoma specimens, suggesting, therefore, they are suitable targets for the multikinase inhibitor sorafenib. Thus, we explored sorafenib activity in patients with relapsed and unresectable osteosarcoma. Experimental design: Patients >14 years, progressing after standard treatment, were eligible to receive 400 mg of sorafenib twice daily until progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) at 4 months. Secondary objectives were PFS, overall survival (OS), clinical benefit rate (CBR), defined as no progression at 6 months and safety. This nonrandomized phase II study used a Simon two-stage design. PFS and OS at 95% confidence intervals (95% CIs) were calculated by the Kaplan-Meier method. All tests were two sided. Results: Thirty-five patients were enrolled. PFS at 4 months was 46% (95% CI 28% to 63%). Median PFS and OS were 4 (95% CI 2-5) and 7 (95% CI 7-8) months, respectively. The CBR was 29% (95% CI 13% to 44%). We observed 3 (8%) partial responses (PRs), 2 (6%) minor responses (18F]2-fluoro-2-deoxy-D-glucose-positron emission tomography responses were observed among SD patients. Sorafenib was reduced or briefly interrupted in 16 (46%) patients and permanently discontinued in one (3%) case due to toxicity. Conclusions: Sorafenib demonstrated activity as a second- or third-line treatment in terms of PFS at 4 months with some unprecedented long-lasting responses. Sorafenib, the first targeted therapy showing activity in osteosarcoma patients, deserves further investigations.
| Original language | English |
|---|---|
| Pages (from-to) | 508-516 |
| Number of pages | 9 |
| Journal | Annals of Oncology |
| Volume | 23 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 2012 |
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Keywords
- Bone neoplasms
- MAPK
- Osteosarcoma
- Relapse
- Sorafenib
- Target therapy
ASJC Scopus subject areas
- Oncology
- Hematology
Cite this
A phase II trial of sorafenib in relapsed and unresectable high-grade osteosarcoma after failure of standard multimodal therapy : An Italian sarcoma group study. / Grignani, G.; Palmerini, E.; Dileo, P.; Asaftei, S. D.; D'ambrosio, L.; Pignochino, Y.; Mercuri, M.; Picci, P.; Fagioli, F.; Casali, P. G.; Ferrari, S.; Aglietta, M.
In: Annals of Oncology, Vol. 23, No. 2, 02.2012, p. 508-516.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A phase II trial of sorafenib in relapsed and unresectable high-grade osteosarcoma after failure of standard multimodal therapy
T2 - An Italian sarcoma group study
AU - Grignani, G.
AU - Palmerini, E.
AU - Dileo, P.
AU - Asaftei, S. D.
AU - D'ambrosio, L.
AU - Pignochino, Y.
AU - Mercuri, M.
AU - Picci, P.
AU - Fagioli, F.
AU - Casali, P. G.
AU - Ferrari, S.
AU - Aglietta, M.
PY - 2012/2
Y1 - 2012/2
N2 - Purpose: After standard multimodal therapy, the prognosis of relapsed and unresectable high-grade osteosarcoma is dismal and unchanged over the last decades. Recently, mitogen-activated protein kinases were shown to be activated in osteosarcoma specimens, suggesting, therefore, they are suitable targets for the multikinase inhibitor sorafenib. Thus, we explored sorafenib activity in patients with relapsed and unresectable osteosarcoma. Experimental design: Patients >14 years, progressing after standard treatment, were eligible to receive 400 mg of sorafenib twice daily until progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) at 4 months. Secondary objectives were PFS, overall survival (OS), clinical benefit rate (CBR), defined as no progression at 6 months and safety. This nonrandomized phase II study used a Simon two-stage design. PFS and OS at 95% confidence intervals (95% CIs) were calculated by the Kaplan-Meier method. All tests were two sided. Results: Thirty-five patients were enrolled. PFS at 4 months was 46% (95% CI 28% to 63%). Median PFS and OS were 4 (95% CI 2-5) and 7 (95% CI 7-8) months, respectively. The CBR was 29% (95% CI 13% to 44%). We observed 3 (8%) partial responses (PRs), 2 (6%) minor responses (18F]2-fluoro-2-deoxy-D-glucose-positron emission tomography responses were observed among SD patients. Sorafenib was reduced or briefly interrupted in 16 (46%) patients and permanently discontinued in one (3%) case due to toxicity. Conclusions: Sorafenib demonstrated activity as a second- or third-line treatment in terms of PFS at 4 months with some unprecedented long-lasting responses. Sorafenib, the first targeted therapy showing activity in osteosarcoma patients, deserves further investigations.
AB - Purpose: After standard multimodal therapy, the prognosis of relapsed and unresectable high-grade osteosarcoma is dismal and unchanged over the last decades. Recently, mitogen-activated protein kinases were shown to be activated in osteosarcoma specimens, suggesting, therefore, they are suitable targets for the multikinase inhibitor sorafenib. Thus, we explored sorafenib activity in patients with relapsed and unresectable osteosarcoma. Experimental design: Patients >14 years, progressing after standard treatment, were eligible to receive 400 mg of sorafenib twice daily until progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) at 4 months. Secondary objectives were PFS, overall survival (OS), clinical benefit rate (CBR), defined as no progression at 6 months and safety. This nonrandomized phase II study used a Simon two-stage design. PFS and OS at 95% confidence intervals (95% CIs) were calculated by the Kaplan-Meier method. All tests were two sided. Results: Thirty-five patients were enrolled. PFS at 4 months was 46% (95% CI 28% to 63%). Median PFS and OS were 4 (95% CI 2-5) and 7 (95% CI 7-8) months, respectively. The CBR was 29% (95% CI 13% to 44%). We observed 3 (8%) partial responses (PRs), 2 (6%) minor responses (18F]2-fluoro-2-deoxy-D-glucose-positron emission tomography responses were observed among SD patients. Sorafenib was reduced or briefly interrupted in 16 (46%) patients and permanently discontinued in one (3%) case due to toxicity. Conclusions: Sorafenib demonstrated activity as a second- or third-line treatment in terms of PFS at 4 months with some unprecedented long-lasting responses. Sorafenib, the first targeted therapy showing activity in osteosarcoma patients, deserves further investigations.
KW - Bone neoplasms
KW - MAPK
KW - Osteosarcoma
KW - Relapse
KW - Sorafenib
KW - Target therapy
UR - http://www.scopus.com/inward/record.url?scp=84856343533&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856343533&partnerID=8YFLogxK
U2 - 10.1093/annonc/mdr151
DO - 10.1093/annonc/mdr151
M3 - Article
C2 - 21527590
AN - SCOPUS:84856343533
VL - 23
SP - 508
EP - 516
JO - Annals of Oncology
JF - Annals of Oncology
SN - 0923-7534
IS - 2
ER -