InterAACT: A multicentre open label randomised phase II advanced anal cancer trial of cisplatin (CDDP) plus 5-fluorouracil (5-FU) vs carboplatin (C...

Date 22 October 2018
Event ESMO 2018 Congress
Session Proffered paper session - Gastrointestinal tumours, colorectal
Topics Anticancer Agents
Anal Cancer
Presenter Sheela Rao
Authors S. Rao1, F. Sclafani2, C. Eng3, M. Grønlie Guren4, R.A. Adams5, A. Benson6, D. Sebag-Montefiore7, E. Segelov8, A. Bryant9, C. Peckitt10, A. Roy11, M.T. Seymour12, J. Welch13, M.P. Saunders14, R. Muirhead15, J. Bridgewater16, S. Falk17, R. Glynne-Jones18, D. Arnold19, D. Cunningham20
  • 1Gi Unit, Royal Marsden Hospital NHS Foundation Trust, SW3 6JJ - London/GB
  • 2Medicine-gi & Lymphoma Unit, The Institute of Cancer Research/Royal Marsden NHS Foundation Trust, SM2 5PT - Sutton/GB
  • 3Department Of Gastrointestinal Medical Oncology,, M. D. Anderson Cancer Center, Houston/US
  • 4Gi Unit, Oslo University Hospital, 424 - Oslo/NO
  • 51division Of Cancer And Genetics, Cardiff University, CF14 4XN - Cardiff/GB
  • 6Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago/US
  • 7Gi Unit, University of Leeds, LS2 9LU - Leeds/GB
  • 8Oncology, Monash Medical Centre, 3168 - Clayton/AU
  • 9Gi Unit, Royal Marsden Hospital NHS Foundation Trust, SM25PT - London/GB
  • 10R&d, Royal Marsden Hospital NHS Foundation Trust, SW3 6JJ - London/GB
  • 11Gi Unit, Flinders Centre for Innovation in Cancer, 5042 - Bedford Park/AU
  • 12Medical Oncology, St. James's University Hospital Leeds, LS9 7TF - Leeds/GB
  • 13Center For Global Health, NCI-CGH, New York/US
  • 14Gi Unit, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 15Oncology, Churchill Hospital, Oxford/GB
  • 16Oncology, University College London Hospitals, London/GB
  • 17Bristol Haematology And Cancer Centre, Bristol University Hospitals NHS Foundation Trust, Bristol/GB
  • 18Radiotherapy, Mount Vernon Cancer Centre, HA6 2RN - Northwood/GB
  • 192. Med. Abteilung, Asklepios Klinik Altona, 22763 - Hamburg/DE
  • 20Medicine, The Institute of Cancer Research/Royal Marsden NHS Foundation Trust, SM2 5PT - Sutton/GB

Abstract

Background

Whilst advanced squamous cell carcinoma of the anal canal (SCCA) is a rare disease incidence has risen by 2%/year for the past decade. There is no consensus on management of these pts who generally have a poor overall survival (OS) and to date no randomised trial has been completed. The combination of fluoropyrimidine /platinum agents is often considered standard 1st line therapy whilst taxanes have shown activity. We conducted a randomised phase II study to establish a standard of care.

Methods

Eligible pts randomised in 1:1 ratio to CDDP (60 mg/m2, D1q21)/5-FU (1000 mg/m2/24h, D1-4q21) or C (AUC 5, D1q28)/P (80 mg/m2, D1,8,15q28). Stratification factors were performance status (PS), extent of disease, HIV status & country. Primary endpoint was response rate (RR). Based on a RR estimate of 40% in the CDDP/5-FU arm, 80 pts were required to detect 10% difference in RR between the 2 arms with 80% power (phase II selection trial pick the winner design). Secondary endpoints include progression-free survival (PFS), OS, toxicity, quality of life & feasibility.

Results

Between 2014-2017, 91 pts were randomised (46 CDDP/5-FU, 45 CP) from 31/60 centres ;Median age 61 yrs ;Female 67%;12% locally advanced, 88% metastatic. RR :57.1% in CDDP/5-FU and 59.0 % in CP. Median PFS: 5.7 mths for CDDP/FU versus 8.1mths for CP, p=0.375. Median OS 12.3 mths for CDDP/FU versus 20 mths for CP, HR 2.0 p =0.014. Grade ≥3 toxicity occurred in 32 pts (76%) in CDDP/5-FU and 30 pts (71%) in CP. Reported Serious Adverse Events : 62% in CDDP/5-FU and 36% in CP, p=0.016.

Conclusions

InterAACT is the first prospective randomised trial in this setting. In this pick the winner design CP demonstrated similar response rate but less toxicity thus is declared the winner. We have successfully demonstrated the feasibility of international collaboration in a rare cancer. These data establish CP as a standard of care for 1st line treatment of advanced SCCA & serve as a future backbone for the addition of novel agents in phase II/III trials.

Clinical trial identification

NCT02051868

Editorial Acknowledgement