medwireNews: A three-cycle regimen of adjuvant chemotherapy with carboplatin, etoposide, and vincristine (CEV) has been shown to be noninferior to the standard six-cycle regimen in patients with pathologic high-risk retinoblastoma.
The primary endpoint of 5-year disease-free survival (DFS) was 90.4% in the three-cycle group and 89.2% in the six-cycle group, equating to a between-group difference of 1.2 percentage points, which was within the noninferiority margin of a 12.0 percentage point difference, report the researchers in JAMA.
Moreover, the shorter regimen was associated with “fewer adverse effects and lower costs,” they highlight.
Taken together, the findings suggest that “3-cycle chemotherapy could become the new standard for unilateral retinoblastoma with high-risk features, potentially replacing the current 6-cycle approach,” writes the team.
The authors of an accompanying commentary in JAMA Ophthalmology say that “[a]lthough a 12% noninferiority margin risks failing to detect a true difference between 3 and 6 cycles, we agree with the authors that given the rarity of retinoblastoma and the lack of prospective randomized clinical trials, this was an acceptable compromise.”
Carol Shields (Thomas Jefferson University, Philadelphia, Pennsylvania, USA) and co-authors continue: “The financial burden of retinoblastoma therapy can lead to treatment abandonment and death. Thus, a 3-cycle regimen of CEV has the potential to save lives.”
The open-label trial was conducted at two premier eye centers in China and included 187 patients (median age 25 months) who had undergone enucleation for unilateral retinoblastoma with high-risk pathologic features, namely massive choroidal infiltration, retrolaminar optic nerve invasion, or scleral infiltration.
The participants were randomly assigned to receive either three or six cycles of adjuvant carboplatin 18.6 mg/kg (or 560 mg/m2 for children aged ≥3 years) on day 1, etoposide 5.0 mg/kg per day (or 150 mg/m2) on days 1 and 2, plus vincristine 0.05 mg/kg (or 1.5 mg/m2) on day 1 of each 21-day cycle, starting within 21 days of enucleation.
After a median follow-up of 79 months, the secondary endpoint of overall survival was also comparable between the groups, with 5-year rates in the three- and six-cycle arms of 91.5% and 89.3%, respectively.
Huasheng Yang (Sun Yat-sen University, Guangzhou, China) and associates report that the incidence of adverse events (AEs) of grade 1 or 2 was significantly lower among patients who received three versus six cycles of CEV, at a respective 78.5% and 95.7%.
They also note that “[t]he cumulative burden of hematological toxicities, including neutropenia and anemia, as well as nonhematological toxicities such as nausea and weight loss, was significantly reduced” with three cycles of chemotherapy.
The commentators point out, however, that “grade 3 to 4 toxic effects were seen in 10% of the participants receiving 3 cycles and 13% of the participants receiving 6 cycles, clearly not proving a definitive difference for these more clinically relevant toxic effects with the 6-cycle regimen.”
The economics favored the shorter regimen though – the direct (chemotherapy, surgery, supportive care, examinations), indirect (accommodation, transport, diet, loss of parental income), and total costs were significantly lower with the three- than six-cycle regimen, by 41.2%, 43.0%, and 42.4%, respectively.
This “is particularly important in lower-income countries in which financial stress can be a barrier to treatment adherence,” say Yang and colleagues.
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JAMA 2024; doi:10.1001/jama.2024.19981
JAMA Ophthalmol 2024; doi:10.1001/jamaophthalmol.2024.4859