Vincristine and topotecan versus carboplatin-, etoposide-, and vincristine-based chemotherapy for ocular salvage in group D and group E intraocular retinoblastoma: A randomized, comparative trial.

Abstract

10002 Background: India has the highest burden of retinoblastoma worldwide. The access to Intra-arterial chemotherapy is limited and systemic chemotherapy remains the standard of care in low-middle income countries(LMIC) like India. There is a need to find alternative systemic chemotherapy due to growing concerns of long-term toxicities with standard Carboplatin and Etoposide based therapy. Topotecan is an attractive option as it is devoid of late toxicities and found to be effective in retinoblastoma. However, the data is very limited. Methods: We did a randomised comparative trial in children with group D/E intraocular retinoblastoma (IORB) to compare 2 different chemotherapy regimens. Between October 2021 and March 2023, participants fulfilling the inclusion criteria were randomised to receive either vincristine, topotecan(VT-arm) or high dose carboplatin, etoposide, and vincristine(HDCEV-arm) chemotherapy every 3-weekly for 6 cycles with focal therapy after 2-cycles. The reassessment was done every two cycles.The primary objective was to compare the treatment failure rates at the end of 6-cycles, which was defined as need for non-protocol therapy, enucleation or external beam radiotherapy(EBRT). The secondary objectives were to compare final globe salvage rates (which includes all forms of therapy except EBRT) and toxicities. Results: Forty(42 eyes) newly diagnosed cases with group D/E IORB were enrolled. Out of which 19 children(20 eyes) received VT and 21(22 eyes) received HDCEV- based regimen. Baseline parameters were comparable in both arms. After a median follow up of 12.4 months (range, 5.7-22.6), the treatment failure rate was significantly less in HDCEV-arm compared to VT-arm (45.5% vs 75%,HR-2.64, 95% CI, 1.13-6.13, p = 0.02). The 24 months enucleation free-survival was 54.5% in HDCEV-arm and 35% in VT-arm (p < 0.01). There were no deaths in any arm and both treatments were tolerated well. However, the incidence of febrile neutropenia (73.6% vs 43%, p = 0.05) and episodes of grade 3/4 diarrhoea (13 vs 4,p = 0.02) was more in VT-arm compared to HDCEV-arm.The response after 4-cycles was comparable with 90% and 85% showing partial response in HDCEV and VT-arm respectively(p = 0.92) but this effect could not be sustained in VT-arm. Conclusions: Administration of Topotecan is feasible even in LMIC setting without therapeutic drug with manageable toxicity in children. VT is inferior to HDCEV in globe salvage and has slightly more toxicity. The initial response achieved with VT could not be translated into globe salvage. There is a need to find alternative therapy and the combination of VT with carboplatin can be an attractive option. Clinical trial information: 2021/09/047121 .