ONCAlert | 2018 SGO Annual Meeting on Women’s Cancer

Afatinib Improves PFS in Advanced Head and Neck Cancer

Published Online: 12:28 PM, Mon September 29, 2014
Jean-Pascal Machiels, MD, a medical oncologist at St. Luc University Clinics in Brussels.

Jean-Pascal Machiels, MD

Afatinib delayed disease progression for approximately one month longer than chemotherapy and helped prevent painful symptoms from worsening for patients with relapsed or metastatic head and neck squamous cell carcinoma (HNSCC), according to clinical trial findings presented at the 2014 ESMO Congress.

Patients treated with the tyrosine kinase inhibitor had a median progression-free survival (PFS) of 2.6 months compared with 1.7 months for participants who received methotrexate in the randomized phase III Lux-Head & Neck 1 trial. Additionally, more patients in the afatinib arm remained alive without progression at 3 months, investigators reported at the conference in Madrid.

“Afatinib is the first oral tyrosine kinase inhibitor to demonstrate efficacy and improved patient-reported outcomes in a phase III trial in this setting,” said Jean-Pascal Machiels, MD, a medical oncologist at St. Luc University Clinics in Brussels. “Investigations with adjuvant afatinib in locally advanced head and neck squamous cell carcinoma following chemoradiation are ongoing.”

Overall survival, a secondary endpoint, did not differ between treatment groups.

Recurrent and metastatic HNSCC has a poor prognosis, and few effective treatment options exist. Not uncommonly, the disease recurs or relapses in the head and neck, a key contributing factor to disease-related symptoms. Additionally, patients often have multiple chronic comorbidities resulting from excessive alcohol and tobacco use, the leading cause of HNSCC in older patients.

Many types of cancer, including HNSCC, exhibit overexpression of epidermal growth factor receptor (EGFR). Afatinib inhibits the entire ErbB family of receptors, including EGFR, human epidermal growth factor receptor 2 (HER2), HER3, and HER4. In 2013, the FDA approved afatinib as a treatment for patients with non–small cell lung cancer with the trade name of Gilotrif.

Key Findings in Trial

To examine the safety and efficacy of afatinib in HNSCC, an international group of investigators enrolled patients with relapsed or metastatic HNSCC that had progressed on first-line platinum-based chemotherapy. Patients were randomized 2:1 to oral afatinib 40 mg daily or intravenous methotrexate 40 mg/m2 weekly.

Data analysis included 483 patients: 322 randomized to afatinib and 161 to methotrexate. The trial’s primary endpoint was PFS, and the principal secondary endpoint was overall survival. Other secondary endpoints were objective response rate, patient-reported outcomes, and safety.

The results showed that afatinib reduced the hazard for progression by 20% compared with methotrexate (P = 0.030). Additionally, patients treated with afatinib had a 3-month PFS of 42.8% versus 30.5% for the methotrexate group.

Median overall survival did not differ significantly between treatment groups: 6.8 months with afatinib and 6.2 months with methotrexate. The disease control rate (response plus stable disease) was significantly higher in the afatinib arm (49.1% vs 38.5%; P = .04).

Other secondary endpoints did not differ significantly between treatment groups. Overall response rate was 10.2% with afatinib and 5.6% with methotrexate. The proportion of patients who had tumor shrinkage with treatment was 34.8% in afatinib-treated patients and 22.4% in the methotrexate group.

Afatinib and methotrexate were associated with different adverse event profiles. The most common grade 3/4 adverse events with afatinib were rash/acne (9.7%) and diarrhea (9.4%), whereas leukopenia (15.6%) and stomatitis (8.1%) occurred most often among the patients randomized to methotrexate.

As compared with the methotrexate group, patients treated afatinib had a significant delay in the time to deterioration of global health status, pain, and swallowing (P £.03 for all comparisons). Additionally, patients in the afatinib group reported significant improvement in pain severity (P = .03 versus methotrexate).

Machiels acknowledged that the results do not apply to patients who have HNSCC associated with human papillomavirus (HPV) infection, which accounts for most new cases of the disease worldwide.

“Most of these patients were older and had head and neck cancer related to excessive use of alcohol and tobacco,” he said.

The modest improvement in PFS and lack of survival advantage with afatinib should not obscure the quality-of-life benefits obtained by patients who received the tyrosine kinase inhibitor, said Giuseppe Curilgiano, MD, PhD, who moderated the press briefing that included Machiels’ presentation.

“In particular, the delay in deterioration of swallowing is important, as most patients with advanced head and neck cancer have swallowing difficulties,” said Curilgiano, who leads a drug development division at the European Institute of Oncology in Milan. “For many patients, delaying the onset of symptoms makes a big difference in their quality of life.”

Curilgiano agreed that the results could not be extrapolated to HPV-positive HNSCC. Clinical trials involving patients with HPV-related cancer would be required to draw conclusions about the efficacy of afatinib in HPV-positive patients.


Machiels J-P, Haddad RI, Fayette J, et al. Afatinib versus methotrexate (MTX) as second-line treatment for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who progressed after platinum-based therapy: primary efficacy results of LUX-Head & Neck 1. Paper presented at: ESMO 2014 Congress; September 26-30, 2014; Madrid, Spain. Abstract LBA29.

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