September 23, 2009 (Berlin, Germany) — Cetuximab (Erbitux) combined with chemotherapy improves survival in patients with nonsmall-cell lung cancer (NSCLC), according to an analysis of 4 randomized phase 3 trials.

The results of the meta-analysis, which were reported here at the 15th Congress of the European CanCer Organization and the 34th European Society for Medical Oncology Multidisciplinary Congress, demonstrated that patients who received cetuximab plus chemotherapy had a 13% lower chance of dying within 3 years of follow-up, compared with those who received chemotherapy alone. This held true regardless of the specific chemotherapy regimen.

In addition, patients who received cetuximab experienced slower disease progression and an increased likelihood of tumor shrinkage.

"The results of this study support the notion that cetuximab works," in NSCLC, said Robert Pirker, MD, professor of medicine at the Medical University of Vienna in Austria. "It strengthens the evidence thus far."

Dr. Pirker, who was approached by Medscape Oncology for independent comment, pointed out that at this time, cetuximab has not yet been approved in Europe for use in NSCLC. "Right now it is used primarily in clinical trials, although there may be some off-label use," he said.

"We are awaiting its approval, and feel it will be of benefit to these patients," he added.

As previously reported by Medscape Oncology, results of the phase 3 FLEX (First-Line Erbitux in Lung Cancer) trial showed that cetuximab added to a regimen of vinorelbine/cisplatin chemotherapy offered a small survival advantage in NSCLC patients. Three other randomized trials demonstrated similar results when cetuximab was added to different platinum doublets.

To confirm the robustness of the efficacy results of these studies, Jean-Louis Pujol, MD, chair of thoracic oncology at Montpelier Academic Hospital and professor of medicine at Montpelier University in France, and colleagues conducted a meta-analysis of these 4 studies.

There were individual data for 2018 patients who participated in the 4 studies, which Dr. Pujol and his team analyzed for overall survival, progression-free survival, and objective response rate.

"When we put all of the populations together, there was consistency, and all histologies were included in this study," said Dr. Pujol.

There were, however, some slight differences in the trials, he pointed out. For example, 2 of the 4 studies required positive immunostaining against epidermal growth-factor receptor for inclusion criteria.

Efficacy Seen at All End Points

The meta-analysis demonstrated a significant benefit across all efficacy end points for patients who received cetuximab in conjunction with their chemotherapy, compared with those who did not.

For overall survival, the hazard ratio (HR) was 0.87, which corresponded to a 13% reduction in the risk for death. This was statistically significant (P = .010).

Dr. Pujol also pointed out that patients receiving cetuximab had a longer median survival (10.3 months for chemotherapy plus cetuximab vs 9.4 months for chemotherapy alone). "The absolute benefit at 1 year was 5%," he said.

The other end points also showed a benefit for cetuximab. For progression-free survival, the HR was 0.899, corresponding to a 10% reduction in risk (P = .038). Patients who received cetuximab also had a higher chance of being responders, with an odds ratio of 1.463 (P < .001).

"This corresponds to an almost 50% greater chance of being a responder," explained Dr. Pujol. The increase rose "from 24% to 36%, and that was highly significant."

Response in Caucasians Significant

A subanalysis was conducted on the basis of ethnicity. "We know that NSCLC behaves differently according to ethnicity, so we felt it was important to look at a subgroup of Caucasians, as they are the prominent ethnic group in Europe," he said.

The researchers observed that there was a statistically significant benefit favoring cetuximab among Caucasians, and it had a more pronounced effect in this group. The HR of 0.84 corresponded to a risk for death of 16%.

Caucasian patients who received combination chemotherapy plus cetuximab proved to have a better prognosis than those who didn't, with a median survival of 9.9 months, compared with 8.8 months for those who didn't. The absolute benefit at 1 year was 6%, and the absolute benefit at 2 years was 4.5%. Both were significant (P = .012).

"This meta-analysis confirms the efficacy of cetuximab for the 3 end points, and the benefit is statistically significant and is more pronounced in the Caucasian population," Dr. Pujol concluded, "with a striking benefit at 1 and 2 years."

15th Congress of the European CanCer Organization (ECCO 15) and the 34th European Society for Medical Oncology (34th ESMO) Multidisciplinary Congress: Abstract 9005. Presented September 22, 2009.

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