CHICAGO—Patients with human papilloma virus (HPV)-associated resectable squamous cell carcinoma of the oropharynx (OPSCC) responded to induction chemotherapy with paclitaxel, cisplatin, and cetuximab followed by low-dose radiation therapy (RT) with cetuximab with minimal toxicities, results of an Eastern Cooperative Oncology Group (ECOG) study reported at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.

At a median follow-up of 16.2 months, progression-free survival (PFS), the primary endpoint, was premature; if 2-year PFS is 85% or better, additional investigations are warranted, noted Shanthi Marur, MD, of the Johns Hopkins University in Baltimore, MD, and colleagues.

An earlier Eastern Cooperative Oncology Group study (E2399) found that induction chemotherapy followed by paclitaxel/three-dimensional radiotherapy (RT) at 70 Gy for 35 fractions over 7 weeks improved 2-year PFS for patients with HPV-positive OPSCC compared with HPV-negative disease (86% vs. 53%; P=0.02). HPV is associated with 60% to 80% of OPSCC cases.

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In this phase II trial (E1308), which compared low dose versus standard dose intensity-modulated radiation therapy (IMRT), the investigators reduced the dose of radiation by 20%, to 54 Gy, in 90 patients with stage III/IVA,B resectable HPV-positive OPSCC. All patients had a clinical complete response to induction chemotherapy, administered as paclitaxel 90 mg/m2 on days 1, 8, and 15; cisplatin 75 mg/m2 on day 1, and cetuximab 250 mg/m2 on days 1, 8, and 15 every 3 weeks for three cycles.

“Primary tumor and involved nodal response to induction chemotherapy were determined independently,” Dr. Marur reported. Secondary endpoints were toxicity, 2-year overall survival, response rates, early and late toxicities, quality of life to assess late toxicities, and correlative tissue and serum biomarkers.

Median age was 57 years (range, 35–73 years); 95% were men and 93%, Caucasian; 91% had a performance status of 0; 46% were never-smokers and 84% were not current smokers. A total of 54% had nodal stage n2A-N2B and 31% were stage N2C.

Ninety-six percent of patients received all three cycles of induction chemotherapy. Those with a clinical complete response received IMRT 54 Gy in 27 fractions with weekly cetuximab; if less than a clinical complete response was achieved, they received 69.3Gy in 33 fractions with weekly cetuximab.

Among the 80 evaluable patients, biopsy at the primary site after baseline measurements excluded an additional seven patients, six of whom had investigator-reported clinical complete response to induction chemotherapy. The primary site clinical complete response rate to induction chemotherapy was 71.3% (57 of 80 evaluable patients). Of these 62 (78%) were treated in the low-dose RT arm.

One-year PFS in the low-dose RT arm (n=62) was 91%; among those who had a clinical complete response (n=52), it was 90%. Among patients who smoked 10 pack-years or less (n=40), 1-year PFS was 97% compared with 84% in those who had a more than 10 pack-year history (n=21). Among the eight patients who experienced treatment failure on low-dose RT, five had a smoking history of at least 10 pack years, two of whom had a more than 40 pack-year history. Site of failure was local in six patients, nodal in three patients, and distant in one patient.

Grade 3/4 toxicities included rash (25%) and neutropenia (11%) and, during concurrent chemoradiotherapy, oral mucositis (31%; grade 3), dysphagia (17%; grade 3), and radiation dermatitis (8%; grade 3); lymphopenia was observed in 1%.

“Overall, induction chemotherapy with paclitaxel, cisplatin, and cetuximab followed by low-dose RT with cetuximab was well-tolerated, with all patients responding and very low-grade toxicities,” Dr. Marur concluded. “A 2-year PFS will be considered worthy of further study.”