Best time to assess complete clinical response after chemoradiotherapy in squamous cell carcinoma of the anus (ACT II): a post-hoc analysis of randomised controlled phase 3 trial

Summary Background Guidelines for anal cancer recommend assessment of response at 6–12 weeks after starting treatment. Using data from the ACT II trial, we determined the optimum timepoint to assess clinical tumour response after chemoradiotherapy. Methods The previously reported ACT II trial was a phase 3 randomised trial of patients of any age with newly diagnosed, histologically confirmed, squamous cell carcinoma of the anus without metastatic disease from 59 centres in the UK. We randomly assigned patients (by minimisation) to receive either intravenous mitomycin (one dose of 12 mg/m2 on day 1) or intravenous cisplatin (one dose of 60 mg/m2 on days 1 and 29), with intravenous fluorouracil (one dose of 1000 mg/m2 per day on days 1–4 and 29–32) and radiotherapy (50·4 Gy in 28 daily fractions); and also did a second randomisation after initial therapy to maintenance chemotherapy (fluorouracil and cisplatin) or no maintenance chemotherapy. The primary outcome was complete clinical response (the absence of primary and nodal tumour by clinical examination), in addition to overall survival and progression-free survival from time of randomisation. In this post-hoc analysis, we analysed complete clinical response at three timepoints: 11 weeks from the start of chemoradiotherapy (assessment 1), 18 weeks from the start of chemoradiotherapy (assessment 2), and 26 weeks from the start of chemoradiotherapy (assessment 3) as well as the overall and progression-free survival estimates of patients with complete clinical response or without complete clinical response at each assessment. We analysed both the overall trial population and a subgroup of patients who had attended each of the three assessments by modified intention-to-treat. This study is registered at controlled-trials.com , ISRCTN 26715889. Findings We enrolled 940 patients from June 4, 2001, until Dec 16, 2008. Complete clinical response was achieved in 492 (52%) of 940 patients at assessment 1 (11 weeks), 665 (71%) of patients at assessment 2 (18 weeks), and 730 (78%) of patients at assessment 3 (26 weeks). 691 patients attended all three assessments and in this subgroup, complete clinical response was reported in 441 (64%) patients at assessment 1, 556 (80%) at assessment 2, and 590 (85%) at assessments 3. 151 (72%) of the 209 patients who had not had a complete clinical response at assessment 1 had a complete clinical response by assessment 3. In the overall trial population of 940 patients, 5 year over