Addition of Panitumumab to Cisplatin/Fluorouracil Improves Progression-free Survival in Patients with Recurrent or Metastatic Head and Neck Cancer
Previous studies have shown that anti-EGFR monoclonal antibody treatment can improve clinical outcomes in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. In the open-label phase III SPECTRUM trial, Jan B. Vermorken, MD, of Antwerp University Hospital and colleagues evaluated the effects of adding panitumumab (Vectibix) to cisplatin/ fluorouracil (5-FU) in first-line treatment of recurrent or metastatic squamous cell carcinoma of the head and neck. The results of the study, published in Lancet Oncology, demonstrated that the addition of panitumumab prolonged progression-free survival but not overall survival. Overall survival was prolonged by panitumumab in the subgroup of patients who had positive findings on the p16-INK4A immunohistochemical assay.
Study Details
In this international trial, 657 patients with distant metastatic or locoregionally recurrent disease considered incurable by surgery or radiotherapy and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned to receive up to six 3-week cycles of cisplatin (100 mg/m2 on day 1) and 5-FU (1,000 mg/m2 on days 1–4) with (n = 327) or without (n = 330) panitumumab (9 mg/kg on day 1). Patients in the panitumumab group could choose to continue maintenance panitumumab every 3 weeks. The primary endpoint was overall survival. In a prospectively defined retrospective analysis, tumor human papillomavirus status as a potential predictor of outcome was assessed using a p16-INK4A (p16) immunohistochemical assay.
Survival Outcomes
Median overall survival was 11.1 months in the panitumumab group and 9.0 months in the chemotherapy group (hazard ratio [HR] = 0.873, P = .1403). Median progression-free survival was 5.8 months and 4.6 months, respectively (HR = 0.780, P = .0036). Appropriate samples for assessing p16 status were available for 443 (67%) patients; of these, 99 (22%) were p16-positive. Among patients with p16-negative tumors, median overall survival was significantly prolonged in the panitumumab group compared with the chemotherapy group (11.7 vs 8.6 months, HR = 0.73, P = .0115). There was no difference in median overall survival between panitumumab patients and chemotherapy patients with p16-positive tumors (11.0 vs 12.6 months, P = .998). In the chemotherapy group, p16-positive patients had a nonsignificant increase in overall survival compared with p16-negative patients (HR = 0.70, 95% confidence interval = 0.47–1.04).
Adverse Events
Grade 3 or 4 adverse events that were more common in the panitumumab group included skin or eye toxicity (19% vs 2%), hypomagnesemia (12% vs 4%), hypokalemia (10% vs 7%), diarrhea (5% vs 1%), and dehydration (5% vs 2%). Treatment-related deaths occurred in 14 patients (4%) in the panitumumab group and 8 (2%) in the control group, with 5 (2%) of the deaths in the panitumumab group being attributed to panitumumab treatment.
The investigators concluded, “Although the addition of panitumumab to chemotherapy did not improve overall survival in an unselected population of patients with recurrent or metastatic squamous cell carcinoma of the head and neck, it improved progression-free survival and had an acceptable toxicity profile. p16 status could be a prognostic and predictive marker in patients treated with panitumumab and chemotherapy. Prospective assessment will be necessary to validate our biomarker findings.”
The study was funded by Amgen Inc.
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