De-escalated adjuvant chemotherapy effective for high-risk retinoblastoma
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Key takeaways:
- Fewer adjuvant chemotherapy cycles benefited infants with unilateral pathologic high-risk retinoblastoma.
- Six cycles increased costs and adverse events compared with three cycles.
A shortened adjuvant chemotherapy regimen improved outcomes for infants with unilateral pathologic high-risk retinoblastoma, according to study results.
Researchers reported improved 5-year DFS among those who received three cycles compared with those who received six cycles.
Prior studies established adjuvant therapy as an effective and important component of retinoblastoma treatment. However, evidence from head-to head trials comparing six cycles vs. three cycles of CEV chemotherapy — which consists of carboplatin, etoposide and vincristine — for treatment of enucleated unilateral retinoblastoma with high-risk pathologic features had been limited.
Huijing Ye, MD, PhD, of Sun Yat-sen University in China, and colleagues conducted a randomized noninferiority trial to assess whether three cycles of CEV is noninferior to six cycles for infants with this cancer type.
The study included 187 infants (median age, 25 months; 44.4% girls) treated at one of two eye centers in China. All infants had undergone enucleation for unilateral retinoblastoma with high-risk pathologic features between August 2013 and March 2024.
Researchers randomly assigned infants to three (n = 94) or six cycles (n = 93) of CEV chemotherapy regimen following enucleation.
DFS served as the primary endpoint, with a 12% noninferiority margin. Secondary endpoints included OS, safety, economic burden and quality of life.
After median follow-up of 79 months (interquartile range, 65.5-102.5), researchers reported 5-year DFS rates of 90.4% for those assigned three cycles and 89.2% for those assigned six cycles (difference = 1.2%; 95% CI, 7.5% to 9.8%), meeting the noninferiority criterion.
Five-year OS rates did not differ significantly between the three-cycle and six-cycle groups (91.5% vs. 89.3%; HR = 0.78; 95% CI, 0.31-1.98).
Infants who received the six-cycle regimen experienced higher rates of any-grade adverse events (95.7% vs. 80.6%), as well as grade 1/grade 2 adverse events (95.7% vs. 78.5%; P < .001).
No treatment-related deaths occurred.
Researchers reported lower cumulative burden of hematologic toxicities in the three-cycle group. Among infants assigned the six-cycle regimen, the frequency of adverse events linked to nausea, vomiting, neutropenia and upper respiratory infections increased from cycles 1 through 3 to cycles 4 through 6.
At 6 months after surgery, results showed a trend toward less decline in emotional, physical and social functioning among infants assigned three cycles. However, quality-of-life outcomes appeared consistent between groups at other time points.
Investigators reported significantly lower total costs (42.4% reduction), direct costs (41.2% reduction) and indirect costs (43% reduction) in the three-cycle group (P < .001) for all.
Researchers acknowledged study limitations, including the study’s open-label design, its criteria for adjuvant therapy — specifically choroidal invasion — and its “notably substantial” 12% noninferiority margin.
“The results suggest that a three-cycle regimen could be as effective as the standard six-cycle treatment regimen, possibly due to inherent or acquired resistance in some tumors,” Ye and colleagues wrote. “All disease-specific events in this study occurred within 20 months, and other studies have noted all events within the first year of follow-up, with a recurrence to death time of about 8 months. This implies that a 2-year follow-up may be adequate to detect disease-specific events in patients [with retinoblastoma] with high-risk features.”
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