CHICAGO — Survival results from the first randomized phase 3 trial to compare cisplatin-radiotherapy with cetuximab-radiotherapy after induction chemotherapy in patients with locally advanced unresectable head and neck cancer remain inconclusive, with both arms showing good locoregional control, greater than 50% at 3 years, attendees at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting were told.1

For all patients, the rate of overall survival was 51.8% (95% CI, 47.27-56.13); median overall survival was 42.2% (95% CI, 33.7-52.4).

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“Due to the excellent survival rates, a much longer follow-up would be needed to perform the formal analysis,” said Ricardo Hitt, MD, PhD, Hospital Universitario Severo Ochoa, Madrid, Spain, on behalf of the Spanish Head and Neck Cancer Group.

The two regimens also showed similar response rates, toxicity, and loco-regional control, all secondary end points.

To date, these results suggest that in patients with unresectable locally advanced head and neck cancer, induction chemotherapy “could select those who are fit and most sensitive” to subsequent chemotherapy, biotherapy, and radiotherapy, he said.

A total of 530 patients age 18 to 72 years, ECOG performance status 0 or 1, with measurable disease and adequate renal and liver function were enrolled in the study and treated with an induction regimen of docetaxel, cisplatin, and 5-fluorouracil (DCF) plus G-CSF.

After at least 2 cycles (range, 2-3), 407 patients with objective response or stable disease were randomly assigned to cisplatin (100 mg/m2 on days 1, 22, and 43) plus radiotherapy (dose 68-72 Gy, in 35 fractions) (n = 205) or cetuximab (400 mg day 1; 250 mg/m2 weekly concurrent with radiotherapy) plus the same radiotherapy scheme (n = 202). Patients were stratified 1:1 by tumor location.

Median age was 56 years; 89% were male, and 70% had an ECOG performance status of 1. A total of 64% had oropharyngeal and hypopharyngeal tumors; 81% were T3/T4 and 76% were N2/N3.

The median number of DCF cycles was 3 (range, 0-3), and response rate was 71%. Grade 3/4 toxicity was observed in 40% of patients, 24% of whom discontinued due to disease progression or toxicity.

After randomization, patients received a median 3 cycles of cisplatin (range, 1-3), 8 cycles of cetuximab (range 1-15), and 70 Gy radiotherapy dose (range, 62-72 Gy).

After treatment with induction therapy, the best response rate was 72.7%; following cisplatin and radiotherapy, this rate was 93.2%; and for cetuximab and radiotherapy, 97.5%.

Grade 3/4 mucositis was 36.2% in the induction arm, 31.7% in the cisplatin arm, and 44.6% in the cetuximab arm. Rates of hematologic toxicity were higher in the cisplatin arm: anemia was 13.7% compared with 0.0% in the cetuximab arm; neutropenia was 4.9% vs 1.0%, respectively; febrile neutropenia was 3.9% vs 1.0%; and thrombocytopenia was 1.5% versus 0.0%.

At a median follow-up of 36 months, locoregional control was 55.6% (95% CI, 48.2-62.4) in the cisplatin arm and 50.1% (42.5-57.2) in the cetuximab arm.

Overall current status of the 519 patients who underwent induction therapy are 269 deaths; of the 250 who remain alive (data missing for 17), 158 have had a complete response; 39, a partial response; 8, stable disease; 24, disease progression; and 4 were not evaluable.

“The possible influence of prognostic factors is still unknown,” Dr. Hitt said, adding that analyses are ongoing.



1. Hitt R, Mesia R, Grau JJ, et al. Randomized phase III trial of induction chemotherapy (ICT) with docetaxel-cisplatin-5fluorouracil (DCF) followed by cisplatin-radiotherapy (CRT) or cetuximab-radiotherapy (CetRT) in patients (pts) with locally advanced unresectable head and neck cancer (LAUHNC). Oral presentation at: 2016 ASCO Annual Meeting; June 3-7, 2016; Chicago, IL.