Results of the phase III Trans-Tasman Radiation Oncology Group 99.03 trial reported in the Journal of Clinical Oncology by MacManus et al indicate that use of systemic therapy following involved-field radiotherapy (IFRT) increased progression-free survival in patients with stage I or II low-grade follicular lymphoma.
In the open-label trial, 150 patients who had undergone staging computed tomography scans and bone marrow biopsies (radiolabeled positron-emission tomography [PET] was not mandatory) from 21 sites in Australia, New Zealand, and Canada were randomized between February 2000 and July 2012 to receive 30 Gy of IFRT with (n = 75) or without (n = 75) systemic therapy. Systemic therapy initially consisted of 6 cycles of cyclophosphamide, vincristine, and prednisolone (CVP; n = 44); from 2006, rituximab (Rituximab) was added to the systemic therapy regimen (R-CVP; n = 31). Randomization was stratified by center, disease stage, age, and from 2006, PET staging. Overall, 75% of patients had stage I disease, median age was 57 years, 52% were male, and 48% were PET staged. The first planned analysis with a minimum potential follow-up of at least 3 years for all patients was performed in July 2016.
After median follow-up of 9.6 years (range = 3.1–15.8 years), progression-free survival was significantly improved in the systemic therapy group vs IFRT alone group (hazard ratio [HR] = 0.57, P = .033); 10-year progression-free survival was 59% vs 41%. The HR for progression-free survival for the 31 patients in the systemic therapy group who received R-CVP vs 31 contemporaneous patients in the IFRT alone group was 0.26 (P = .045); none of 26 patients receiving R-CVP with follow-up > 3.5 years had relapse. In the period before rituximab was given, the HR was 0.70 (P = .24). Factors associated with better progression-free survival among all patients included fewer involved regions (P = .047) and PET staging (P = .056). Histologic transformation occurred in 4 vs 10 patients (P = .1). Overall survival at 10 years was 95% vs 87% (P = .40).
The investigators concluded, “Systemic therapy with R-CVP after IFRT reduced relapse outside radiation fields and significantly improved [progression-free survival]. IFRT followed by immunochemotherapy is more effective than IFRT in early-stage [follicular lymphoma].”
The study was supported by the Cancer Council of Victoria, Australasian Leukaemia and Lymphoma Group, Peter MacCallum Cancer Centre, Amgen, and Roche.
Michael MacManus, MBBCh, of the Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, is the corresponding author for the Journal of Clinical Oncology article.
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