PLATO-ACT4
Standard versus reduced-dose chemoradiotherapy in anal cancer (PLATO-ACT4): short-term results of a phase 2 randomised controlled trial
Phase 2N = 163
- Population
- Patients aged at least 16 years with ECOG performance status 0-1 and early-stage anal cancer: T1-2 (up to 4 cm), N0-Nx, M0
- Design
- Phase 2, prospective, multicentre, open-label, two-arm non-comparative randomised trial of reduced-dose intensity-modulated radiotherapy (rd-IMRT: 41.4 Gy in 23 fractions) in early-stage anal cancer, registered as ISRCTN88455282. 163 patients were recruited from 28 UK tertiary centres between 24 April 2017 and 1 December 2020 and randomised 1:2 (stratified by T stage, N stage, gender, HIV status and site) to standard-dose IMRT (sd-IMRT: 50.4 Gy in 28 fractions) or rd-IMRT, each with concurrent mitomycin and capecitabine. 160 patients (55 and 105) were in the primary analysis. The primary outcome is 3-year locoregional failure, which is awaited; this report is the pre-planned modified intention-to-treat analysis of secondary endpoints 6 months after treatment end.
- Primary endpoint
- Locoregional failure
- Arms
- Standard-dose IMRT with mitomycin and capecitabine (control, n = 55): 50.4 Gy in 28 fractions with concurrent mitomycin and capecitabine
- Reduced-dose IMRT with mitomycin and capecitabine (experimental, n = 105): 41.4 Gy in 23 fractions with concurrent mitomycin and capecitabine
- People
- Gilbert A, PLATO trial study group
Δ Complete response of the primary tumour+5 pointsΔ Grade 3 or worse acute toxicity−11 points
Show the numbers
| Endpoint | Analysis | Reduced-dose IMRT with mitomycin and capecitabine | Standard-dose IMRT with mitomycin and capecitabine | Effect |
|---|---|---|---|---|
| Complete response of the primary tumourPre-planned modified intention-to-treat analysis (160 patients: 55 standard-dose, 105 reduced-dose); 6-month response available for 53 and 97 patientsComplete clinical response 6 months after the end of treatment, a pre-planned secondary endpoint. | interimGilbert 2025 | 92% | 87% | 46 of 53 patients with standard-dose IMRT and 89 of 97 with reduced-dose IMRT. The trial is non-comparative, so no formal comparison of the arms is made; the primary outcome (3-year locoregional failure) is not yet reported. |
| Grade 3 or worse acute toxicityPre-planned modified intention-to-treat analysis (160 patients: 55 standard-dose, 105 reduced-dose) | interimGilbert 2025 | 35% | 46% | 25 of 55 patients with standard-dose IMRT and 37 of 105 with reduced-dose IMRT. Radiotherapy interruptions of 3 days or more: 26% (14 of 55) vs 15% (16 of 105); chemotherapy modifications: 49% (27 of 55) vs 37% (39 of 105); serious adverse events: 15% (8 of 55) vs 10% (10 of 105). Patient-reported outcomes for most issues deteriorated at the end of treatment and resolved to baseline by 6 weeks in both groups; poorer sexual function for men and women was observed at 6 months after standard-dose IMRT. |
| Endpoint | Analysis | Reduced-dose IMRT with mitomycin and capecitabine | Standard-dose IMRT with mitomycin and capecitabine | Effect |
|---|---|---|---|---|
| Complete response of the primary tumourPre-planned modified intention-to-treat analysis (160 patients: 55 standard-dose, 105 reduced-dose); 6-month response available for 53 and 97 patientsComplete clinical response 6 months after the end of treatment, a pre-planned secondary endpoint. | interimGilbert 2025 | 92% | 87% | 46 of 53 patients with standard-dose IMRT and 89 of 97 with reduced-dose IMRT. The trial is non-comparative, so no formal comparison of the arms is made; the primary outcome (3-year locoregional failure) is not yet reported. |
| Grade 3 or worse acute toxicityPre-planned modified intention-to-treat analysis (160 patients: 55 standard-dose, 105 reduced-dose) | interimGilbert 2025 | 35% | 46% | 25 of 55 patients with standard-dose IMRT and 37 of 105 with reduced-dose IMRT. Radiotherapy interruptions of 3 days or more: 26% (14 of 55) vs 15% (16 of 105); chemotherapy modifications: 49% (27 of 55) vs 37% (39 of 105); serious adverse events: 15% (8 of 55) vs 10% (10 of 105). Patient-reported outcomes for most issues deteriorated at the end of treatment and resolved to baseline by 6 weeks in both groups; poorer sexual function for men and women was observed at 6 months after standard-dose IMRT. |