As reported in the Journal of Clinical Oncology by Dunkel et al, the Children’s Oncology Group (COG) ARET0321 trial has shown high 1-year event-free survival rates with intensive multimodality therapy in patients with stage II, III, and IVa extraocular retinoblastoma.
In the international trial, 57 evaluable patients with a median age at diagnosis of 32 years were enrolled between 20008 and 2004, including 19 with stage II/III disease (orbital disease, optic nerve involvement at the surgical margin, or regional nodal disease), 18 with stage IVa disease (metastatic disease not involving the central nervous system [CNS]), and 20 with stage IVb disease (CNS disease: metastases or trilateral disease). All patients received four cycles of induction therapy with vincristine, cisplatin, cyclophosphamide, and etoposide, with mesna and filgrastim support. Patients with stage II/III disease then received involved field radiotherapy (45 Gy). Patients with stage IVa or IVb disease with at least partial response to induction received one cycle of high-dose carboplatin, thiotepa, and etoposide with autologous hematopoietic stem cell support; those with residual tumor after chemotherapy received radiotherapy.
Intensive multimodality therapy is highly effective for patients with regional extraocular retinoblastoma and stage IVa metastatic retinoblastoma. Although the study met its aim for stage IVb, more effective therapy is still required for patients with CNS involvement.— Dunkel et al
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The primary outcome measure was 1-year event-free survival; the hypothesis was that treatment could improve rates to 70%, 70%, and 20% in the II/III, IVa, and IVb cohorts based on outcomes in historical controls.
In the stage II/III cohort, 1-year event-free survival was 88.1% (90% confidence interval [CI] = 66.6%–96.2%; P = .003 vs historical controls). Overall survival at 1 year was 88.1% (90% CI = 66.6%–96.2%). Event-free and overall survival rates at 3 years were the same as at 1 year.
In the stage IVa cohort, 1-year event-free survival was 82.6% (90% CI = 61.0%–92.9%; P < .001 vs historical controls). Event-free survival at 3 years was 76.7% (90% CI = 54.6%–89.1%). The 1- and 3-year overall survival rates were 88.5% (90% CI = 67.7%–96.3%) and 76.7% (90% CI = 54.6%–89.1%).
In the stage IVb cohort, 1-year event-free survival was 28.3% (90% CI = 12.7%–46.2%; P = .002 vs historical controls). Event-free survival at 3 years was 14.2% (90% CI = 3.7%–31.5%). The 1- and 3-year overall survival rates were 42.1% (90% CI = 23.6%–59.5%) and 12.3% (90% CI = 3.0%–28.4%).
As stated by the investigators, “Toxicity was significant as expected and included two therapy-related deaths.”
The investigators concluded, “Intensive multimodality therapy is highly effective for patients with regional extraocular retinoblastoma and stage IVa metastatic retinoblastoma. Although the study met its aim for stage IVb, more effective therapy is still required for patients with CNS involvement.”
Ira J. Dunkel, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by National Clinical Trial Network grants and others. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.