Outcome of patients with recurrent osteosarcoma enrolled in seven phase II trials through Children's Cancer Group, pediatric oncology Group, and Children's Oncology Group: Learning from the past to move forward

Joanne P. Lagmay, Mark D. Krailo, Ha Dang, Ae Rang Kim, Douglas S. Hawkins, Orren Beaty, Brigitte C. Widemann, Theodore Zwerdling, Lisa Bomgaars, Anne Marie Langevin, Holcombe E. Grier, Brenda Weigel, Susan M. Blaney, Richard Gorlick, Katherine A. Janeway

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Purpose The use of radiographic response as the primary end point in phase II osteosarcoma trials may limit optimal detection of treatment response because of the calcified tumor matrix. We performed this study to determine if time to progression could be used as an end point for subsequent studies. Patients and Methods We performed a retrospective analysis of outcome for patients with recurrent/refractory osteosarcoma enrolled in one of seven phase II trials conducted by the Children's Oncology Group and predecessor groups from 1997 to 2007. All trials used RECIST or WHO radiographic response criteria and the primary end point of response rate. The following potential prognostic factors-age, trial, number of prior chemotherapy regimens, sex, and race/ethnicity-were evaluated for their impact on event-free survival (EFS). We used data from a phase II study (AOST0221) of patients with osteosarcoma who were given inhaled granulocyte-macrophage colony-stimulating factor with first pulmonary recurrence who had an EFS as well as biologic end point to determine the historical disease control rate for patients with fully resected disease. Results In each included trial, the drugs tested were determined to be inactive on the basis of radiographic response rates. The EFS for 96 patients with osteosarcoma and measurable disease was 12% at 4 months (95% CI, 6% to 19%). There was no significant difference in EFS across trials according to number of prior treatment regimens or patient age, sex, and ethnicity. The 12-month EFS for the 42 evaluable patients enrolled in AOST0221 was 20% (95% CI, 10% to 34%). Conclusion The EFS was uniformly poor for children with recurrent/refractory osteosarcoma in these single-arm phase II trials. We have now constructed baseline EFS outcomes that can be used as a comparison for future phase II trials for recurrent osteosarcoma.

Original languageEnglish (US)
Pages (from-to)3031-3038
Number of pages8
JournalJournal of Clinical Oncology
Volume34
Issue number25
DOIs
StatePublished - Sep 1 2016
Externally publishedYes

Fingerprint

Osteosarcoma
Disease-Free Survival
Learning
Pediatrics
Neoplasms
Granulocyte-Macrophage Colony-Stimulating Factor
Limit of Detection
Recurrence
Drug Therapy
Lung
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Outcome of patients with recurrent osteosarcoma enrolled in seven phase II trials through Children's Cancer Group, pediatric oncology Group, and Children's Oncology Group : Learning from the past to move forward. / Lagmay, Joanne P.; Krailo, Mark D.; Dang, Ha; Kim, Ae Rang; Hawkins, Douglas S.; Beaty, Orren; Widemann, Brigitte C.; Zwerdling, Theodore; Bomgaars, Lisa; Langevin, Anne Marie; Grier, Holcombe E.; Weigel, Brenda; Blaney, Susan M.; Gorlick, Richard; Janeway, Katherine A.

In: Journal of Clinical Oncology, Vol. 34, No. 25, 01.09.2016, p. 3031-3038.

Research output: Contribution to journalArticle

Lagmay, JP, Krailo, MD, Dang, H, Kim, AR, Hawkins, DS, Beaty, O, Widemann, BC, Zwerdling, T, Bomgaars, L, Langevin, AM, Grier, HE, Weigel, B, Blaney, SM, Gorlick, R & Janeway, KA 2016, 'Outcome of patients with recurrent osteosarcoma enrolled in seven phase II trials through Children's Cancer Group, pediatric oncology Group, and Children's Oncology Group: Learning from the past to move forward', Journal of Clinical Oncology, vol. 34, no. 25, pp. 3031-3038. https://doi.org/10.1200/JCO.2015.65.5381
Lagmay, Joanne P. ; Krailo, Mark D. ; Dang, Ha ; Kim, Ae Rang ; Hawkins, Douglas S. ; Beaty, Orren ; Widemann, Brigitte C. ; Zwerdling, Theodore ; Bomgaars, Lisa ; Langevin, Anne Marie ; Grier, Holcombe E. ; Weigel, Brenda ; Blaney, Susan M. ; Gorlick, Richard ; Janeway, Katherine A. / Outcome of patients with recurrent osteosarcoma enrolled in seven phase II trials through Children's Cancer Group, pediatric oncology Group, and Children's Oncology Group : Learning from the past to move forward. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 25. pp. 3031-3038.
@article{b26e64ba86254da5843d2e993ed96beb,
title = "Outcome of patients with recurrent osteosarcoma enrolled in seven phase II trials through Children's Cancer Group, pediatric oncology Group, and Children's Oncology Group: Learning from the past to move forward",
abstract = "Purpose The use of radiographic response as the primary end point in phase II osteosarcoma trials may limit optimal detection of treatment response because of the calcified tumor matrix. We performed this study to determine if time to progression could be used as an end point for subsequent studies. Patients and Methods We performed a retrospective analysis of outcome for patients with recurrent/refractory osteosarcoma enrolled in one of seven phase II trials conducted by the Children's Oncology Group and predecessor groups from 1997 to 2007. All trials used RECIST or WHO radiographic response criteria and the primary end point of response rate. The following potential prognostic factors-age, trial, number of prior chemotherapy regimens, sex, and race/ethnicity-were evaluated for their impact on event-free survival (EFS). We used data from a phase II study (AOST0221) of patients with osteosarcoma who were given inhaled granulocyte-macrophage colony-stimulating factor with first pulmonary recurrence who had an EFS as well as biologic end point to determine the historical disease control rate for patients with fully resected disease. Results In each included trial, the drugs tested were determined to be inactive on the basis of radiographic response rates. The EFS for 96 patients with osteosarcoma and measurable disease was 12{\%} at 4 months (95{\%} CI, 6{\%} to 19{\%}). There was no significant difference in EFS across trials according to number of prior treatment regimens or patient age, sex, and ethnicity. The 12-month EFS for the 42 evaluable patients enrolled in AOST0221 was 20{\%} (95{\%} CI, 10{\%} to 34{\%}). Conclusion The EFS was uniformly poor for children with recurrent/refractory osteosarcoma in these single-arm phase II trials. We have now constructed baseline EFS outcomes that can be used as a comparison for future phase II trials for recurrent osteosarcoma.",
author = "Lagmay, {Joanne P.} and Krailo, {Mark D.} and Ha Dang and Kim, {Ae Rang} and Hawkins, {Douglas S.} and Orren Beaty and Widemann, {Brigitte C.} and Theodore Zwerdling and Lisa Bomgaars and Langevin, {Anne Marie} and Grier, {Holcombe E.} and Brenda Weigel and Blaney, {Susan M.} and Richard Gorlick and Janeway, {Katherine A.}",
year = "2016",
month = "9",
day = "1",
doi = "10.1200/JCO.2015.65.5381",
language = "English (US)",
volume = "34",
pages = "3031--3038",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "25",

}

TY - JOUR

T1 - Outcome of patients with recurrent osteosarcoma enrolled in seven phase II trials through Children's Cancer Group, pediatric oncology Group, and Children's Oncology Group

T2 - Learning from the past to move forward

AU - Lagmay, Joanne P.

AU - Krailo, Mark D.

AU - Dang, Ha

AU - Kim, Ae Rang

AU - Hawkins, Douglas S.

AU - Beaty, Orren

AU - Widemann, Brigitte C.

AU - Zwerdling, Theodore

AU - Bomgaars, Lisa

AU - Langevin, Anne Marie

AU - Grier, Holcombe E.

AU - Weigel, Brenda

AU - Blaney, Susan M.

AU - Gorlick, Richard

AU - Janeway, Katherine A.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Purpose The use of radiographic response as the primary end point in phase II osteosarcoma trials may limit optimal detection of treatment response because of the calcified tumor matrix. We performed this study to determine if time to progression could be used as an end point for subsequent studies. Patients and Methods We performed a retrospective analysis of outcome for patients with recurrent/refractory osteosarcoma enrolled in one of seven phase II trials conducted by the Children's Oncology Group and predecessor groups from 1997 to 2007. All trials used RECIST or WHO radiographic response criteria and the primary end point of response rate. The following potential prognostic factors-age, trial, number of prior chemotherapy regimens, sex, and race/ethnicity-were evaluated for their impact on event-free survival (EFS). We used data from a phase II study (AOST0221) of patients with osteosarcoma who were given inhaled granulocyte-macrophage colony-stimulating factor with first pulmonary recurrence who had an EFS as well as biologic end point to determine the historical disease control rate for patients with fully resected disease. Results In each included trial, the drugs tested were determined to be inactive on the basis of radiographic response rates. The EFS for 96 patients with osteosarcoma and measurable disease was 12% at 4 months (95% CI, 6% to 19%). There was no significant difference in EFS across trials according to number of prior treatment regimens or patient age, sex, and ethnicity. The 12-month EFS for the 42 evaluable patients enrolled in AOST0221 was 20% (95% CI, 10% to 34%). Conclusion The EFS was uniformly poor for children with recurrent/refractory osteosarcoma in these single-arm phase II trials. We have now constructed baseline EFS outcomes that can be used as a comparison for future phase II trials for recurrent osteosarcoma.

AB - Purpose The use of radiographic response as the primary end point in phase II osteosarcoma trials may limit optimal detection of treatment response because of the calcified tumor matrix. We performed this study to determine if time to progression could be used as an end point for subsequent studies. Patients and Methods We performed a retrospective analysis of outcome for patients with recurrent/refractory osteosarcoma enrolled in one of seven phase II trials conducted by the Children's Oncology Group and predecessor groups from 1997 to 2007. All trials used RECIST or WHO radiographic response criteria and the primary end point of response rate. The following potential prognostic factors-age, trial, number of prior chemotherapy regimens, sex, and race/ethnicity-were evaluated for their impact on event-free survival (EFS). We used data from a phase II study (AOST0221) of patients with osteosarcoma who were given inhaled granulocyte-macrophage colony-stimulating factor with first pulmonary recurrence who had an EFS as well as biologic end point to determine the historical disease control rate for patients with fully resected disease. Results In each included trial, the drugs tested were determined to be inactive on the basis of radiographic response rates. The EFS for 96 patients with osteosarcoma and measurable disease was 12% at 4 months (95% CI, 6% to 19%). There was no significant difference in EFS across trials according to number of prior treatment regimens or patient age, sex, and ethnicity. The 12-month EFS for the 42 evaluable patients enrolled in AOST0221 was 20% (95% CI, 10% to 34%). Conclusion The EFS was uniformly poor for children with recurrent/refractory osteosarcoma in these single-arm phase II trials. We have now constructed baseline EFS outcomes that can be used as a comparison for future phase II trials for recurrent osteosarcoma.

UR - http://www.scopus.com/inward/record.url?scp=84983487344&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84983487344&partnerID=8YFLogxK

U2 - 10.1200/JCO.2015.65.5381

DO - 10.1200/JCO.2015.65.5381

M3 - Article

C2 - 27400942

AN - SCOPUS:84983487344

VL - 34

SP - 3031

EP - 3038

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 25

ER -