Background
Post-hoc analysis of the ACT-II phase III RCT (940 patients). Evaluated 5-year progression-free survival (PFS) outcomes by allocated treatment group (MMC vs cisplatin; maintenance vs no maintenance). ACT-II used a 2×2 factorial design with 5-FU + RT backbone, comparing MMC vs CDDP concurrent chemotherapy and maintenance 5-FU + CDDP vs no maintenance. This report provides mature 5-year outcomes and investigates whether any patient subgroup benefits from maintenance chemotherapy.
Interventions and follow up
Arm A: 5-FU + MMC + RT ± maintenance 5-FU + cisplati
Arm B: 5-FU + cisplatin + RT ± maintenance 5-FU + cisplati
Primary endpoint: 5-year progression-free survival (post-hoc analysis)
mFollow up: 5 year
Arm B: 5-FU + cisplatin + RT ± maintenance 5-FU + cisplati
Primary endpoint: 5-year progression-free survival (post-hoc analysis)
mFollow up: 5 year
Results
5-year PFS — MMC vs cisplatin: 72.3% vs 72.0% — not significant
5-year PFS — maintenance vs no maintenance: 73.7% vs 71.8% — not significant
5-year OS — maintenance vs none: 84.9% vs 83.7% — not significant
No subgroup benefit from maintenance: Consistent across T-stage, N-stage, HIV status, tumor site
5-year PFS — maintenance vs no maintenance: 73.7% vs 71.8% — not significant
5-year OS — maintenance vs none: 84.9% vs 83.7% — not significant
No subgroup benefit from maintenance: Consistent across T-stage, N-stage, HIV status, tumor site
Adverse events
Main adverse events: Maintenance chemotherapy added hematologic toxicity (grade 3–4 leukopenia in maintenance recipients) without survival benefit. Early treatment response at 11 weeks (not allocated treatment) was the key predictor of long-term outcome.
Conclusions
At 5-year follow-up, MMC and cisplatin have equivalent PFS and OS when used concurrently with 5-FU–based CRT. Maintenance 5-FU + cisplatin provides no benefit in any patient subgroup. Early treatment response (11-week assessment) is a stronger outcome predictor than chemotherapy backbone.
Key Limitations
Key Limitations: Post-hoc analysis design — not powered for the endpoints evaluated at this report. Subgroup analyses (T/N stage, HIV status) should be interpreted cautiously given their exploratory nature. Split-course RT schedule limits generalizability to modern continuous-course IMRT centers. No biomarker analysis for potential predictors of maintenance benefit.
Clinical Context
This post-hoc report definitively ends the question of maintenance chemotherapy for anal cancer. The finding that early response at 11 weeks predicts long-term outcome supports efforts to use response-adaptive treatment strategies. Modern practice has shifted to IMRT (RTOG 0529) and oral capecitabine in place of infusional 5-FU (Goodman IJROBP 2017), with no role for maintenance therapy.