Dinutuximab Beta Versus Naxitamab in the Treatment of Relapsed/Refractory Neuroblastoma in Patients with Stable Disease, Minor Response or Partial Response and Disease in Bone or Bone Marrow: Systematic Review and Matching-Adjusted Indirect Comparison

Abstract

Objective: Dinutuximab beta (DB) and naxitamab (NAXI) with GM-CSF are used for maintenance treatment of relapsed/refractory neuroblastoma. The objective of this study was to systematically assess comparative efficacy of the two therapies within their designated indications in accordance with established clinical guidelines. Methods: Relevant evidence was identified in systematic literature review. Individual patient data (IPD) from prospective clinical trials of DB were assessed and data on patients with disease in bone or bone marrow, as assessed in MRI, CT, mIBG or biopsy, with incomplete response to previous therapy were included. Patients with complete response, progressive disease and/or soft tissue disease were excluded. DB population was adjusted for sex, MYCN amplification, disease type (relapsed, refractory), and disease site (bone marrow and/or bone) to balance aggregated characteristics of NAXI population. More characteristics were included in sensitivity analyses, including DB treatment without interleukin-2, as currently recommended. Overall response rate (ORR) was assessed as best response. Results: Aggregated data for NAXI from Study 201 (n = 52) and Study 230 (n = 38) and IPD from DB studies (APN311-202, APN311-304, c = 77) met the inclusion criteria. Compared to NAXI, DB significantly extended progression-free survival (PFS): hazard ratio, DB vs. NAXI of 0.47 (95% CI: 0.26 to 0.87, p = 0.015). ORR was 60.1% (95% CI: 48.5% to 71.6%) for DB vs. 43.3% (33.1% to 53.6%) for NAXI (ORR odds ratio, DB vs. NAXI was 1.97, 95% CI: 1.02 to 3.80, p = 0.044). Sensitivity analyses and unadjusted comparisons supported the results. Conclusion: In the indirect comparison, dinutuximab beta significantly extended PFS and increased ORR compared to naxitamab.

Keywords: dinutuximab beta; matching-adjusted indirect comparison; naxitamab; relapsed/refractory neuroblastoma; systematic review.

Figure 1

Patient flow diagram. CR, complete response; FAS, full analysis set; MAIC, matched-adjusted indirect comparison.

Figure 2

MAIC of PFS (DB with or without IL-2). Kaplan–Meier plots of compared arms: (1) naxitamab arm (Study 201); (2) DB unadjusted (Studies APN311-304, APN311-202, V1+V2 and APN311-202, V3); (3) DB arm weighted with variables: refractory, female, MYCN amplification, bone marrow only, bone and bone marrow (base-case analysis); (4) DB arm weighted with additional variables in MAIC: prior radiotherapy, Black race, % MYCN missing, % INSS stage 3 and % missing INSS (sensitivity analysis #1).

Figure 3

MAIC of PFS (DB without IL-2): (1) naxitamab arm (Study 201); (2) DB without IL-2 unadjusted (sensitivity analysis #2); (3) DB without IL-2 arm weighted with variables: refractory, female, MYCN amplification, bone marrow only, bone and bone marrow (sensitivity analysis #3); (4) DB without IL-2 arm weighted with additional variables in MAIC: prior radiotherapy, Black race, % MYCN missing, % INSS stage 3 and % missing INSS (sensitivity analysis #4).