Adding the monoclonal anti-EGFR antibody panitumumab to chemotherapy did not significantly improve overall survival for patients with recurrent and/or metastatic head and neck cancer, according to Phase-III trial results reported at the 35th Congress of the European Society for Medical Oncology (ESMO) in Milan, Italy.

The results come from the SPECTRUM trial, which included 657 patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Participants were randomly assigned to either cisplatin-5-fluorouracil (PF) or PF plus panitumumab (Vectibix?, Amgen).

?The primary endpoint that we had hoped to reach, having a statistically better overall survival by adding panitumumab to the chemotherapy regimen, was not reached,? said lead investigator Professor Jan Vermorken of Antwerp University Hospital in Belgium.

Median overall survival was 11.1 months in the panitumumab arm, compared to 9.0 months in the chemotherapy-alone arm. This difference was not statistically significant (HR=0.87, 95% Cl: 0.73?1.05; p=0.14).

?The outcome of the trial was surprising,? Prof Vermorken said. ?However, the risk of having a negative result in terms of overall survival was never unimaginable considering the differences in supportive care available in different countries, differences in the types of patients treated and the availability of further treatment once they were off the study protocol.? The trial is the largest global study conducted so far in this setting and included patients from Western Europe, Eastern Europe, Asia Pacific, South America and North America.

Although overall survival was not significantly different between the treatment groups, patients receiving panitumumab experienced a longer progression-free survival –with medians of 5.8 months for patients in the panitumumab arm and 4.6 months for patients in the chemotherapy-alone arm (HR = 0.78, 95% Cl: 0.66?0.92; descriptive p=0.004). The overall response rate was 36% in the panitumumab arm, compared to 25% for patients who received only chemotherapy (descriptive p=0.007). Since the primary endpoint was not met, secondary endpoints were not tested for statistical significance per the pre-specified statistical analysis plan.

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The safety profile was as expected for PF in combination with panitumumab. Serious adverse events were seen in 48% of panitumumab patients, compared to 43% of chemotherapy-alone patients.

The researchers are currently undertaking pre-planned analyses of patient subgroups based on whether they had prior radiotherapy or chemoradiation, the site of their primary tumor, tumor grading and patient performance status, Prof Vermorken said. Moreover, we will look whether outcome is any different in different areas in the world.

Other studies investigating the drug?s use in combination with other treatments for head and neck cancer are due to report findings soon, Prof Vermorken added. ?Although this study did not reach its primary endpoint, there was clearly activity observed.?

?Further studies integrating panitumumab into multimodal treatment are in development,? Prof Vermorken said. ?We expect to report on the outcome of studies in primary disease and as second-line treatment for recurrent or metastatic head and neck cancers in the near future.?

Dr Marshall Posner, director of Head and Neck Medical Oncology at The Tisch Cancer Institute, Mount Sinai School of Medicine, New York, commented: ?Although the statistical analysis of the trial did not conclude a statistically significant survival benefit to panitumumab, the data demonstrate that there was a real biological effect. This was seen as an increase in progression-free survival that was significant, and a highly significant difference in response rate.?

?The availability of alternative EGFR antibody therapy for the control population may have influenced the outcome,? Dr Posner said. ?I think the data show this drug is active and effective and the progression-free survival data are compelling.?

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