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Home » Head & Neck Cancer

Oncology NEWS International. Vol. 16 No. 7
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First-Line Erbitux Ups H&N Survival

July 1, 2007

Treatment with cetuximab(Drug information on cetuximab) continued until progression or unacceptable toxicity. Crossover was not allowed. The primary endpoint was overall survival.

The majority of patients (about 60%) had well-differentiated or moderately differentiated tumors. Most (about 80%) had received prior radiotherapy, and about 40% had prior chemotherapy (allowed for locally advanced SCCHN if completed 6 months prior to study entry). Following randomization, about two-thirds of patients received cisplatin(Drug information on cisplatin) (based on individual institution choice).

Study Results

Survival analysis was conducted after 343 events were reached. Median survival was 10.1 months for patients in the cetuximab plus chemotherapy arm vs 7.4 months in the chemotherapy-alone arm (HR 0.797, P = .036). One-year survival was 39% in the experimental arm vs 31% in the control arm.

A subgroup analysis did not reveal any predictors of poor response to cetuximab, including prior radiotherapy or current treatment with cisplatin vs carboplatin(Drug information on carboplatin), although the evidence for benefit in the patients receiving cisplatin was somewhat greater than for those receiving carboplatin.

Safety Analysis

An interim safety analysis on 429 patients (median number of cycles, four) showed a similar incidence of grade 3-4 adverse events (72% in the experimental arm vs 69% in the control arm), with a slightly higher incidence in the cetuximab arm of grade 3-4 vomiting/diarrhea and, as expected, acne-like rash and infusion reactions, Dr. Vermorken reported.

A total of 9% of cetuximab-treated patients vs 6% of controls discontinued therapy because of adverse events. Deaths were mostly a result of tumor progression, not toxic death, Dr. Vermorken said. Data on clinical response and time to tumor progression will be available at a later date.

"The survival benefit is among the longest ever seen in a large clinical trial among these patients," Dr. Vermorken concluded. "With new targeted agents such as cetuximab, we are on the brink of changing the way we treat patients with head and neck cancers."

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VantagePoint

Crossover Trials in Palliative Setting Needed

MARSHALL R. POSNER, MD— The "impressive 35% increase in median survival" with addition of cetuximab (Erbitux) to standard chemotherapy of recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) is "the first demonstration of a survival improvement in the palliative setting for any therapy in head and neck cancer," said Dr. Posner, associate professor of medicine, Harvard Medical School, and medical director, Head and Neck Oncology Program, Dana-Farber Cancer Institute.

He noted that the trial could not be duplicated today because there was no crossover to single-agent cetuximab. "We have to ask, if this had been allowed, what would the impact have been on survival?... I believe that a crossover trial in recurrent disease will be necessary; cetuximab gives a 10% response rate and stabilization in a fraction of patients with cisplatin/carboplatin-resistant disease," Dr. Posner said.

It would also have been interesting to assess the impact on survival of the continued cetuximab in the experimental arm following six cycles of chemotherapy, Dr. Posner added. Because of tumor cell kinetics, he said, one must be mindful of timing issues in combined modality therapy; drug A may confer a survival advantage over drug B that can disappear when treatment is discontinued.

Other important questions for future trials, which should probably be studied in crossover trials in the palliative setting, he said, concern synergy between cetuximab and 5-FU, or between cetuximab and cisplatin/taxane regimens, and efficacy of combinations including other targeted agents

Because toxicity of platinum/5-FU regimens (eg, neuropathy with cisplatin and bone marrow suppression with both platinum agents) precludes long-term use, "cetuximab may offer better palliation for patients, as it can be given in a prolonged fashion," Dr. Posner said. The survival outcome in the current study, he emphasized, "has major implications in curative therapy as well," adding that consecutive chemotherapy "may be better for palliation but not cure" in patients with locally advanced head and neck cancer.






 
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