Three Chemotherapy Cycles Non-Inferior to Six for High-Risk Retinoblastoma

• A randomized clinical trial involving 187 patients with high-risk retinoblastoma showed that three cycles of carboplatin, etoposide, and vincristine (CEV) chemotherapy were non-inferior to six cycles.
• Five-year disease-free survival rates were 90.4% in the 3-cycle group and 89.2% in the 6-cycle group, meeting the non-inferiority margin criterion of 12%.
• The 6-cycle regimen was associated with a higher incidence of adverse events, reduced quality of life scores, and increased costs compared to the 3-cycle regimen.
• The findings suggest that three cycles of CEV chemotherapy is an effective adjuvant treatment option for unilateral, high-risk retinoblastoma, potentially reducing treatment burden.

A recent study published in JAMA demonstrates that three cycles of carboplatin, etoposide, and vincristine (CEV) chemotherapy are non-inferior to the standard six cycles for patients with pathologically high-risk retinoblastoma. The randomized clinical trial, conducted across two centers in China, offers a potential reduction in treatment duration and associated toxicities without compromising efficacy.

The study enrolled 187 patients with unilateral retinoblastoma exhibiting high-risk pathological features, including massive choroidal infiltration, retrolaminar optic nerve invasion, or scleral infiltration, who had undergone enucleation. Participants were randomized to receive either three or six cycles of CEV chemotherapy. The primary endpoint was disease-free survival, with a non-inferiority margin of 12%.

Non-Inferiority Demonstrated

After a median follow-up of 79 months, the five-year disease-free survival rate was 90.4% in the three-cycle group and 89.2% in the six-cycle group. This difference of 1.2% (95% CI, -7.5% to 9.8%) met the pre-defined non-inferiority criterion (P=.003). These results suggest that a shorter chemotherapy regimen is just as effective in preventing disease recurrence.

Reduced Adverse Events and Improved Quality of Life

Importantly, the study also found that the six-cycle group experienced a higher frequency of adverse events, greater reduction in quality of life scores, and increased costs compared with the three-cycle group. This suggests that reducing the number of chemotherapy cycles could significantly improve the patient experience and reduce the economic burden associated with treatment.

Implications for Clinical Practice

"Adjuvant therapy is an important and effective treatment for retinoblastoma," the authors noted. The findings from this trial provide compelling evidence that a three-cycle CEV regimen is an efficacious adjuvant chemotherapy regimen for individuals diagnosed with pathologically high-risk retinoblastoma. This approach could minimize exposure to chemotherapy and improve the overall well-being of young patients.

The study's results could lead to a change in clinical practice, with oncologists potentially opting for the shorter, three-cycle regimen for patients with high-risk retinoblastoma. This shift could reduce the burden of treatment for these young patients and their families, while maintaining high rates of disease-free survival.