Carboplatin Plus Paclitaxel New Standard for Advanced Anal Cancer

By Marilynn Larkin

June 24, 2020

NEW YORK (Reuters Health) - In patients with advanced anal cancer, carboplatin plus paclitaxel was associated with less toxicity and a trend toward longer survival compared with cisplatin and fluorouracil (FU), in a midstage study.

These results "have led to an immediate change in patient care for advanced anal cancer patients," Dr. Sheela Rao of Royal Marsden Hospital in Sutton, UK told Reuters Health by email. Guidelines from both the European Society for Medical Oncology and the US National Comprehensive Cancer Network "chang(ed) as a result of our research," she said.

"While treatment with cisplatin and 5-fluorouracil was generally considered a reasonable option for advanced anal cancer, we now know that carboplatin and paclitaxel is more effective and better tolerated," she said. "In our study, these patients lived seven months longer overall and experienced less treatment side effects."

Dr. Rao and colleagues randomly assigned 91 patients who had not received systemic therapy for advanced anal cancer to intravenous cisplatin 60 mg/m2 (day 1) plus FU 1,000 mg/m2 (days 1-4) every 21 days or carboplatin (area under the curve, 5; day 1) plus paclitaxel 80 mg/m2 (days 1, 8, and 15) every 28 days for 24 weeks, until disease progression, intolerable toxicity, or withdrawal of consent.

Participants' mean age was 60; 71% were women in the carboplatin plus paclitaxel group, and 63% in cisplatin plus FU. Most had metastatic disease, and the median follow-up was 28.6 months.

As reported in the Journal of Clinical Oncology, the objective response rate was 59% for carboplatin plus paclitaxel versus 57% for cisplatin plus FU.

The median progression-free survival was 8.1 months for carboplatin/paclitaxel versus 5.7 months for cisplatin plus FU. Similarly, as Dr. Rao noted, the median overall survival favored carboplatin/paclitaxel: 20 months versus 12.3 months.

Fewer serious adverse events were noted in the carboplatin/paclitaxel arm (36% versus 62%).

Selected grade-3 infections for carboplatin/paclitaxel versus cisplatin plus FU included neutropenia (29% vs. 19%); fatigue (10% vs. 19%); and infection (12% vs. 14%).

Dr. Rao said, "This approach of a global collaborative network was successful in delivering results in a timely manner and will be used to pursue future trials in metastatic anal cancer. It highlights the importance of international collaboration in rare cancers to deliver meaningful results for these patients."

Dr. Marwan Fakih, section head of gastrointestinal medical oncology at City of Hope in Duarte, California, commented in an email to Reuters Health, "Even though this is a small randomized phase 2 clinical trial, the differences in treatment tolerability coupled by a trend towards an improvement in overall survival (OS) clearly positions (carboplatin plus paclitaxel) as a new standard for the first-line treatment of advanced squamous cell cancer of the anus."

That said, he added, "This study has limitations. First, the selection of a 60 mg/m2 dose level for cisplatin may not be adequately justified. This dose is lower than several other cisplatin doses on prior studies (75 to 100 mg/m2)."

"Nonetheless, and even at 60 mg/m2, considerable toxicities were noted, suggesting that higher doses may not have been readily feasible without a 5-FU dose reduction," he said. "Second, the study is not powered enough to answer a superiority question in terms of progression-free survival or overall survival; no superior regimen was confirmed as far as efficacy."

"It is important to note that while (carboplatin plus paclitaxel) appears safer than 5-FU/cisplatin, both regimens were associated with a relatively high rate of infectious complications," he said.

SOURCE: Journal of Clinical Oncology, online June 12, 2020.