Up to now, patients with inoperable anal cancer, a rare disease, have not had a standard-of-care treatment; palliative care has been the routine for them.
Now, results from InterAAct, the first international prospective randomized trial in advanced anal cancer, are published by the Journal of Clinical Oncology.
The trial compared two conventional chemotherapy treatments in 91 patients. The objective response rate (ORR), the primary endpoint, was the same between treatments.
The ORR for cisplatin plus 5-fluorouracil (5FU) was 57% versus 59% for carboplatin plus paclitaxel. However, cisplatin-5FU was associated with significantly more adverse events (62%) versus carboplatin-paclitaxel (36%).
Additionally, carboplatin-paclitaxel was associated with improved overall survival (20 months) compared to cisplatin-5FU (12.3 months).
"The InterAAct trial identifies carboplatin-paclitaxel as the optimal chemotherapy regimen in the first-line setting for inoperable anal cancer," said lead United States investigator Cathy Eng, MD (Vanderbilt-Ingram Cancer Center).
Carboplatin-paclitaxel was associated with less toxicity and a trend towards improved survival, which suggests that it should become the standard of care for these patients, and the backbone for future phase three trials."
Cathy Eng, MD, Lead United States Investigator, Vanderbilt-Ingram Cancer Center
Anal cancer is rare and accounts for less than three percent of all gastrointestinal cancers. Advanced, inoperable anal cancer is even rarer, accounting for about 10 percent of those cases.
For these patients, the prognosis is poor, with relative five-year survival rates of approximately 30 percent.
The study enrolled 91 patients between December 2013 and November 2017 in Australia, Germany, Norway, the United Kingdom, and the United States.
Due to the rarity of the disease, it was necessary to establish a global network of investigators to design and conduct trials for metastatic anal cancer patients, provide patients with access to these new strategies, and to enroll patients in a timely manner.
The International Rare Cancers Initiative (IRCI) formed the Anal Cancer Working Group, a global collaborative network, to achieve these goals.
Established in 2011, the founding members of IRCI include the US National Cancer Institute, UK National Institute for Health Research, Cancer Research UK, and European Organisation for Research and Treatment of Cancer.
Subsequently, the French National Cancer Institute, Canadian Cancer Trials Group, Japan Clinical Oncology Group, and Clinical Oncology Society of Australia have all joined.
"The Anal Cancer Working Group has proven to be a successful global collaborative network for research in this rare disease," said Al B. Benson, III, MD (Northwestern University-Robert H. Lurie Comprehensive Cancer Center and co-chair of the IRCI Anal Cancer Working Group).
"With the successful completion of the InterAAct trial in a timely way, the Anal Cancer Working Group has established its feasibility and will pursue future trials."
In the United States, ECOG-ACRIN Cancer Research Group led the trial with funding from the National Cancer Institute (NCI) through its National Clinical Trials Network. The NCI is part of the National Institutes of Health.
Patients who had not received prior systemic chemotherapy for locally recurrent inoperable or metastatic anal cancer were eligible to participate in the InterAAct trial.
The 91 patients enrolled in the trial were randomly assigned in a one-to-one fashion: 46 patients to receive intravenous cisplatin 60mg/m2 (day 1) 5FU 1000mg /m2 (days 1-4) every 21 days, and 45 patients to receive carboplatin (AUC=5, day 1) paclitaxel (80mg/m2 days 1, 8, 15) every 28 days.
Median follow up for all patients was 28.6 months. Patients remained on treatment until disease progression, intolerable toxicity, or withdrawal of consent.
Sheila Rao, MD of Royal Marsden Hospital in London UK, is the global lead investigator for the InterAAct trial.
The ClinicalTrials.gov identifier for the InterAAct anal cancer trial is NCT02051868.
Rao, S., et al. (2020) International Rare Cancers Initiative Multicenter Randomized Phase II Trial of Cisplatin and Fluorouracil Versus Carboplatin and Paclitaxel in Advanced Anal Cancer: InterAAct. Journal of Clinical Oncology. doi.org/10.1200/JCO.19.03266.