The incidence of anal cancer has been increasing over the past decade, but currently still only constitutes 0.5% of all cancer diagnoses in the United States.¹Symer MM & Yeo HL. F1000Res. 2018; 7: F1000 Faculty Rev-1572. When anal cancer metastasises, the prognosis is poor, with relative 5-year survival rates of approximately 30%.²Rao S, et al. J Clin Oncol. 2020 Jun 12;JCO1903266. The current standard of care for metastatic anal cancer is cisplatin-based chemotherapy combined with 5-fluorouracil (5-FU).¹Symer MM & Yeo HL. F1000Res. 2018; 7: F1000 Faculty Rev-1572. However, no randomised clinical trial investigating the optimal chemotherapy regimen for this disease has been conducted.²Rao S, et al. J Clin Oncol. 2020 Jun 12;JCO1903266. The InterAAct trial was launched to investigate cisplatin plus FU against carboplatin plus paclitaxel in advanced anal cancers, and full results were recently published in the Journal of Clinical Oncology.²Rao S, et al. J Clin Oncol. 2020 Jun 12;JCO1903266.

The international, open-label, multicentre randomised phase II InterAAct trial aimed to set a standard of care for anal cancer and establish a cytotoxic backbone for future trials.²Rao S, et al. J Clin Oncol. 2020 Jun 12;JCO1903266. Participating patients were aged ≥18 years with histologic confirmation of locally recurrent inoperable or metastatic epidermoid anal squamous carcinoma.²Rao S, et al. J Clin Oncol. 2020 Jun 12;JCO1903266. HIV-positive patients were included if they were receiving highly active antiretroviral therapy and CD4 count was ≥200μ/L, or CD4 count ≤200μ/L.²Rao S, et al. J Clin Oncol. 2020 Jun 12;JCO1903266. Patients were allocated 1:1 to receive either cisplatin plus FU, or carboplatin plus paclitaxel. Patients were treated for 24 weeks or until disease progression, intolerable toxicity, or withdrawal of consent.²Rao S, et al. J Clin Oncol. 2020 Jun 12;JCO1903266.^ The primary endpoint was overall response rate (ORR), and secondary endpoints included progression-free survival (PFS), overall survival (OS), and assessments of adverse events (AEs).²Rao S, et al. J Clin Oncol. 2020 Jun 12;JCO1903266.

A total of 91 patients were recruited, and 45 assigned to carboplatin plus paclitaxel, and 46 to cisplatin plus FU.²Rao S, et al. J Clin Oncol. 2020 Jun 12;JCO1903266. Majority of patients had metastatic disease and were HIV negative.²Rao S, et al. J Clin Oncol. 2020 Jun 12;JCO1903266. ECOG PS was 0/1 in most patients. After a median follow-up of 28.6 months, ORR was 57% for cisplatin plus FU, vs 59% for carboplatin plus paclitaxel.²Rao S, et al. J Clin Oncol. 2020 Jun 12;JCO1903266. Median PFS was not statistically different, at 5.7 months for cisplatin plus FU, vs 8.1 months with carboplatin plus paclitaxel.²Rao S, et al. J Clin Oncol. 2020 Jun 12;JCO1903266. Median OS was 12.3 months for cisplatin plus FU, compared with 20 months for carboplatin plus paclitaxel, with a trend towards significant difference.²Rao S, et al. J Clin Oncol. 2020 Jun 12;JCO1903266.

Patients in the cisplatin plus FU arm experienced more nausea, vomiting, mucositis, and diarrhoea, while patients receiving carboplatin plus paclitaxel had more neutropenia and anaemia.²Rao S, et al. J Clin Oncol. 2020 Jun 12;JCO1903266. There were more serious AEs with cisplatin plus FU vs carboplatin plus paclitaxel (62% vs 36%; p=0.016).²Rao S, et al. J Clin Oncol. 2020 Jun 12;JCO1903266. However, as the trial aimed to set a standard of care, although no significant difference in ORRs was observed, the significantly fewer serious AEs and improved toxicity profile led to the conclusion that carboplatin plus paclitaxel should be considered the new standard of care in untreated advanced anal cancer.²Rao S, et al. J Clin Oncol. 2020 Jun 12;JCO1903266.

Reference

1. Symer MM & Yeo HL. F1000Res. 2018; 7: F1000 Faculty Rev-1572.
2. Rao S, et al. J Clin Oncol. 2020 Jun 12;JCO1903266.