In an International Rare Cancers Initiative phase II trial (InterAAct) reported in the Journal of Clinical Oncology, Rao et al found that carboplatin/paclitaxel was associated with less serious toxicity and a trend toward improved overall survival vs cisplatin/fluorouracil in chemotherapy-naive patients with advanced anal cancer.

Study Details

In the open-label trial, 91 patients from sites in the United Kingdom, Australia, Norway, and the United States were randomly assigned between December 2013 and November 2017 to receive cisplatin at 60 mg/m² on day 1 plus fluorouracil at 1,000 mg/m² on days 1 to 4 every 21 days (n = 46) or carboplatin at area under the curve = 5 on day 1 plus paclitaxel at 80 mg/m² on days 1, 8, and 15 every 28 days (n = 45) for 24 weeks or until disease progression or intolerable toxicity. Randomization was stratified by Eastern Cooperative Oncology Group performance status, locally advanced vs metastatic disease status, HIV status, and region.

The primary endpoint was investigator-assessed objective response rate on Response Evaluation Criteria in Solid Tumors version 1.1 criteria in the modified intent-to-treat population.

Treatment Outcomes

Of the randomly assigned patients, 42 in each group received study treatment and constituted the safety population. The modified intent-to-treat population comprised 39 patients in the carboplatin/paclitaxel group and 35 in the cisplatin/fluorouracil group.

Median follow-up was 28.6 months. Objective response rates were 57% (20 of 35 patients) in the cisplatin/fluorouracil group, with complete response in six patients (17.1%), compared with 59% (23 of 39 patients) in the carboplatin/paclitaxel group, including complete response in five patients (12.8%). The difference did not reach the predefined clinically relevant difference of 10% between groups.

Median progression-free survival was 5.7 months (95% confidence interval [CI] = 3.3–9.0 months) in the cisplatin/fluorouracil group vs 8.1 months (95% CI = 6.6–8.8 months) in the carboplatin/paclitaxel group; the unadjusted hazard ratio was 1.27 (P = .375) and the hazard ratio after adjustment for stratification factors was 1.17 (P = .564).

Median overall survival was 12.3 months (95% CI = 9.2–17.7 months) in the cisplatin/fluorouracil group vs 20 months (95% CI = 12.7 months–not reached) in the carboplatin/paclitaxel group; the unadjusted hazard ratio was 2.00 (P = .014) and the adjusted hazard ratio was 1.78 (P = .059).

Adverse Events

Serious adverse events occurred in 62% of patients in the cisplatin/fluorouracil group vs 36% of the carboplatin/paclitaxel group (P = .016). Grade 3 or 4 adverse events occurred in 76% vs 71% of patients; mucositis (26% vs 0%), nausea (17% vs 2%), vomiting (12% vs 5%), and diarrhea (5% vs 2%) were more common with cisplatin/fluorouracil, whereas neutropenia (29% vs 19%) and anemia (10% vs 5%) were more common with carboplatin/paclitaxel.

The investigators concluded, “This is the first international randomized trial to our knowledge conducted in chemotherapy-naive advanced anal cancer. Although there was no difference in objective response rate, the association with clinically relevant reduced toxicity and a trend toward longer survival suggest that carboplatin plus paclitaxel should be considered as a new standard of care.”

Sheela Rao, MD, of the GI Unit, Department of Medicine, Royal Marsden Hospital, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by Cancer Research UK, Australian Gastro-Intestinal Trials Group, and Eastern Cooperative Oncology Group-American College of Radiology Imaging Network. For full disclosures of the study authors, visit ascopubs.org.