Jury out on adding cetuximab to CRT for anal carcinoma
medwireNews: Two phase II trials evaluating the combination of cetuximab and chemoradiotherapy (CRT) in anal carcinoma patients, with or without HIV infection, find that although cetuximab addition is associated with lower locoregional failure (LRF) rates than reported historically, it comes with a toxicity cost.
The researchers explored cetuximab addition in the anal carcinoma setting as the epidermal growth factor receptor inhibitor has been shown to boost survival in radiotherapy-treated patients with locally advanced oropharyngeal cancer, a malignancy that is generally associated with human papillomavirus infection, as is squamous cell carcinoma of the anal canal (SCCAC).
In both trials, published in the Journal of Clinical Oncology, patients with stage I–III SCCAC were given two cycles of cisplatin and fluorouracil alongside radiation and concurrent cetuximab once a week for 8 weeks. One of the key differences between the trials was that one enrolled patients without HIV whereas the other was restricted to those with HIV infection.
The first study, E3205, recruited 61 immunocompetent patients, 23% of whom had LRF at 3 years as assessed by binomial proportion estimation using the prespecified endpoint (LRF, death due to disease or treatment within 3 years, or <3 years of follow-up without LRF). By Kaplan–Meier analysis, the 3-year LRF rate was 21%.
Joseph Sparano (Montefiore Medical Center, New York, USA) and colleagues point out that these rates are lower than those observed in previous reports of CRT alone, at up to 35%.
However, “toxicity was substantial,” they add, with diarrhea (68%) the most frequent adverse event of grade 3 or 4, followed by neutropenia (50%), nausea (32%), dehydration (32%), hypokalemia (24%), infection (18%), anemia (15%), and thrombocytopenia (12%). One of the three deaths that occurred within 30 days of treatment completion was considered possibly related to treatment.
The second study AMC045, also led by Joseph Sparano, comprised 45 patients with HIV infection. The 3-year LRF rate was 42% by binomial proportional estimation with the predefined endpoint (LRF or alive without LRF and followed for <3 years) and 20% by the Kaplan–Meier method. The former was “substantially higher”, says the team, because the definition included patients lost to follow-up as failures (12 of the 19 LRF events).
Toxicity was again substantial, with 26% of patients experiencing a grade 4 adverse event and two treatment-related deaths, both within a month of initiating therapy. The most common grade 3 or 4 toxicities were similar to those reported in E3205, but the incidence tended to be lower.
Highlighting that this is the first study to prospectively evaluate CRT in patients with SCCAC and HIV infection, the study authors propose that “SCCAC in HIV-infected individuals may be treated with curative intent similar to immunocompetent individuals.”
With regard to the addition of cetuximab, both trials arrive at a similar conclusion – that, although the reduction in LRF rates is promising, the substantial toxicity and approximately 20% recurrence rate indicate “the continued need for more effective and less toxic therapies.”
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