CHICAGO—Panitumumab plus accelerated fractionation radiotherapy (AFX) was not superior to standard fractionation radiotherapy (SFX) with concurrent cisplatin (CIS) in locoregionally advanced squamous cell carcinoma of the head and neck, results of a phase 3 study concluded at the 2015 American Society of Clinical Oncology (ASCO) annual meeting.
Median follow-up was 46.4 months, and non-inferiority was not proven; “therefore, the primary end point was not met,” said Lillian L. Siu, MD, of Princess Margaret Cancer Centre in Toronto, ON, Canada.
Concurrent cisplatin with radiation therapy (RT) is standard of care in this patient population, and concurrent administration of an anti-EGFR monoclonal antibody with RT has been found to increase survival compared with RT alone.
Previously, a subgroup analysis had demonstrated the benefit of combining the anti-EGFR antibody cetuximab with AFX compared to SFX; however, limited prospective data are available comparing bioradiotherapy (e.g., panitumumab plus RT) to standard cisplatin with RT.
From December 2008 to November 2011, the NCIC Clinical Trials Group HN.6 study investigators randomly assigned 320 patients with TanyN+M0 or T3-4N0M0 LA-SCCHN to SFX (70 Gy/35 over 7 weeks) plus cisplatin 100 mg/m2 intravenously for 3 doses on weeks 1, 4, and 7 (Arm A, 156 patients) versus AFX (70 Gy/35 over 6 weeks) plus panitumumab 9 mg/kg intravenously for 3 doses on weeks -1, 3, and 6 (Arm B, 159 patients). Five patients did not receive study treatment.
Median follow-up was 46.4 months (range: 0.1-64.3 months). “Due to an observed declining event rate, the protocol was amended to analyze data with a clinical cut-off date of October 31, 2014,” Dr. Sui reported.
Median age was 56 years (range: 35-80 years); 84% were male and 71% had an ECOG PS of 0. The primary sites of head and neck cancer were oropharynx (81%), larynx (11%), hypopharynx (6%), and oral cavity (2%). More than half, 58%, of patients had a smoking history of greater than 10 pack-years. Among the 259 patients with oropharyngeal cancer, p16 status was known in 217 (84%); 176 (81%) were positive and 41 (19%) were negative.
A total of 93 progression-free survival events occurred. The 2-year progression-free survival was 73% (95% CI: 65%, 79%) in Arm A and 76% (95% CI: 68%, 82%) in Arm B; the hazard ratio (HR) was 0.95 (95% CI: 0.6, 1.5; P=0.83).
“The upper bound of HRs 95% CI exceeded the prespecified non-inferiority margin, therefore noninferiority of panitumumab plus AFX over cisplatin plus SFX was not proven,” Dr. Siu said.
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The 2-year overall survival rate was 85% (95% CI: 78%, 90%) in Arm A and 88% (95% CI: 82%, 92%) in Arm B (HR 0.89; 95% CI: 0.54, 1.48; P=0.66). By multivariable analysis, anatomic location, ECOG PS, p16 status, and T category all were significant predictors of progression-free survival (P<0.05), Dr. Sui reported.
The incidence of any grade 3 or higher non-hematologic adverse event (AE) was 88% in Arm A and 91% in Arm B (P=0.25).
“When comparing the 2 arms, the cisplatin plus SFX arm had slightly more hearing and GI toxicity, whereas, panitumumab plus AFX had more skin and mucositis toxicity, as expected,” Dr. Siu concluded.
- Siu LL, Waldron JN, Chen BE, et al. Phase III randomized trial of standard fractionation radiotherapy (SFX) with concurrent cisplatin (CIS) versus accelerated fractionation radiotherapy (AFX) with panitumumab (PMab) in patients (pts) with locoregionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN): NCIC Clinical Trials Group HN.6 trial. J Clin Oncol. 2015;33:(suppl; abstr 6000).