MILAN – Panitumumab plus chemotherapy with cisplatin and 5-fluorouracil proved clinically active, but failed to boost overall survival significantly in first-line recurrent or metastatic head and neck cancer in the global, phase III SPECTRUM trial.
The primary end point of median overall survival showed a statistically insignificant increase from 9.0 months with chemotherapy alone to 11.1 months with the addition of panitumumab (Vectibix) (hazard ratio, 0.87; log-rank P = .14).
Dr. Jan Vermorken
Subgroup analysis revealed, however, that the effect of panitumumab, an anti–epidermal growth factor receptor (EGFR) monoclonal antibody, was not the same for all patients in the international study, lead author Dr. Jan Vermorken said at the annual congress of the European Society for Medical Oncology.
Regional differences were observed, suggesting a greater benefit in patients from North/South America (HR, 0.69) and Western Europe (HR, 0.73) than in those in Eastern Europe (HR, 1.11). Asian Pacific patients fell somewhere in the middle (HR, 0.99).
About 45% of patients in each arm used some form of subsequent antitumor activity once off the study protocol, but differences cropped up here as well. The use of cytotoxic chemotherapy was imbalanced at 30% in the panitumumab arm vs. 25% in the chemotherapy arm, while twice as many patients in the chemotherapy arm (12% vs. 6%) received subsequent targeted systemic therapy driven largely by the use of anti-EGFR monoclonal antibodies, observed Dr. Vermorken of the Antwerp University Hospital in Edegem, Belgium.
“It’s clear this is the first analysis shown to you, and it’s also very clear that further analyses need to be done to identify subgroups that may have greater benefit than others with the combination of panitumumab with platinum-based chemotherapy,” he said.
SPECTRUM was conducted at 120 sites in 26 countries, and randomized 657 patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck to six 21-day cycles of cisplatin 100 mg/m2 on day 1 plus 5-FU 1,000 mg/m2 on days 1-4 with or without panitumumab 9 mg/kg on day 1.
Carboplatin was substituted for cisplatin because of severe neurotoxicity or a decrease in creatinine clearance in 21% of the 327 panitumumab patients and 26% of the 330 chemotherapy patients. Also, 33% of patients in the experimental arm opted to remain on panitumumab 9 mg/kg every 3 weeks, for a median of 11 weeks.
The median time to disease progression was significantly longer in patients receiving panitumumab at 5.8 months vs. 4.6 months with chemotherapy alone (log-rank P = .004, descriptive only; HR, 0.78), Dr. Vermorken said.
The objective response rate was 36% in the experimental arm vs. 25% in the control arm (P = .007, descriptive only). A complete response was achieved by 2% of patients in the experimental and control arms; partial responses in 35% and 24%, respectively; and stable disease in 46% and 47%.
The disease control rate also favored panitumumab at 82%, vs. 72% for chemotherapy alone (P = .004, descriptive only).
The safety profile of the experimental arm was in line with other trials of panitumumab and comparable with the use of other monoclonal antibodies in combination with chemotherapy, Dr. Vermorken said. Grade 3 and 4 events occurred in 31% and 15% of the panitumumab group, and in 18% and 8% of the chemotherapy group. Infusion reactions of any grade occurred in 3% of the panitumumab group and 2% of the chemotherapy group.
“The utility of this [triplet] appears significant,” said Dr. Marshall Posner, who was invited to discuss the late-breaking abstract. “The toxicity appears to be manageable, there are no infusion reactions, and the every three-week dosing makes this a somewhat easier agent to give than cetuximab.”
He suggested that the lack of survival advantage with panitumumab may be due to limited accessibility in some populations, notably the Eastern Europeans, to anti-EGFR antibodies, particularly cetuximab (Erbitux). In addition, cultural and regional differences in their cancer and the management of their care may have confounded survival.
What is not known is whether the oropharyngeal site, which has proved to do better in several other trials, did better in SPECTRUM and how well the triplet will work in second-line monotherapy, said Dr. Posner, medical director of the head and neck medical oncology program and cancer clinical trials office at Mount Sinai Medical Center in New York.
Amgen Inc. supported the trial. Dr. Vermorken reported participating in advisory boards for and receiving honoraria from Amgen, Merck-Serono, Lilly, Boehringer-Ingelheim, and Sanofi-Aventis. Two coinvestigators reported employee/stockholder relationships with Amgen. Dr. Posner disclosed consulting for several pharmaceutical companies.