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Multidisciplinary Head and Neck Cancer Symposium

Tanguy Y. Seiwert, MD, assistant professor of Medicine, University of Chicago Medicine, discusses the impact of immunotherapy agents as treatment of patients with head and neck cancer.

Immunotherapy agents are proving to be quite active in the field of head and neck cancer, with 20% to 25% response rates in patients with both HPV-positive and HPV-negative disease, Seiwert explains. However, the key benefit with PD-1 agents is survival, he says. In heavily pretreated patients, median survival is approximately 10 months with immunotherapy.

Given the exciting phase III data with nivolumab in head and neck cancer, Seiwert predicts that the FDA will approve both nivolumab and pembrolizumab in 2016.

View more from the 2016 Multidisciplinary Head and Neck Cancer Symposium

Tanguy Y. Seiwert, MD, assistant professor of Medicine, University of Chicago Medicine, discusses the impact of immunotherapy agents as treatment of patients with head and neck cancer. 

Dr. Seiwert on Immunotherapy in Head and Neck Cancer

Concurrent chemoradiation significantly improved overall survival (OS) compared with radiation therapy alone for elderly patients with locally advanced head and neck cancers, according to a large analysis of the National Cancer Data Base (NCDB) presented at the 2016 Multidisciplinary Head and Neck Cancer Symposium.

In the study, the 5-year OS rate was 30.3% with chemoradiation versus 15.2% with radiation alone for patients >70 years (HR, 0.59; 95% CI, 0.55-0.63, 

 <.001). In a propensity score matching analysis, the 5-year OS rate was 26.4% for chemoradiation versus 18.1% with radiation alone (HR, 0.73; 95% CI, 0.66-0.80; 

“The addition of chemotherapy can improve survival dramatically, even for those who are elderly,” senior study author Sana Karam, MD, PhD, an assistant professor of radiation oncology at the University of Colorado School of Medicine in Aurora, Colorado, said during a presentation of the data. “Our results clearly show that there is a significant overall survival benefit with the addition of concurrent chemoradiation.”

In the study, data were examined from 5265 patients treated with definitive radiation therapy alone (n = 3604) or in combination with chemotherapy (n = 1661). Radiation was delivered in 1.2 to 2.0 Gy fractions, for a total of 66 to 81.6 Gy. Patients were eligible for the chemoradiation arm if they had started chemotherapy within 14 days of receiving radiation. The NCDB did not provide the type of chemotherapy administered.

All patients examined in the study had stage III and IV tumors of the oropharynx, larynx, and hypopharynx. All tumors were either node positive T1-2 or T3-4, N0-3. The median age in the chemoradiation arm was 75 years (range, 71-90). In the radiation alone arm, the median age was 77 years (range, 71-90).

OS was assessed using univariate and multivariate cox regression analysis. Additionally, propensity score matching and recursive partitioning analyses were conducted on the data to rule out any confounding factors, such as age, Charlson comorbidity score, T-stage, and N-stage.

In the recursive partitioning analyses, improvement in OS was associated with patient age of ≤81 years, a low comorbidity (CD) score, and either T1-2/N2-3 or T3-4/N0-3 disease. “The patients who benefit the most are those younger than age 80 with early T stage but advanced nodal or advanced T stage and any nodal and they have to be healthy,” said Karam.

According to the abstract from the meeting, in a multivariate subgroup analysis, those aged <79 years experienced a 20% reduction in the risk of death with chemoradiation versus radiation alone (HR, 0.80; 

 = .001). Those below age 79 with a CD score of 0-1 had a 16% reduction in risk (HR, 0.84; 

 = .002), and those with stage III/IV disease had a 23% reduction in the risk of death with chemoradiation (HR, 0.77; 

OS was not improved with the addition of chemotherapy for those over the age of 81. Additionally, OS was not improved in patients aged 71 to 80 with T1-2/N1 tumors and a CD score of 0-1 and those aged 71 to 80 with T3-4/N1+ tumors with a CD score of more than CD1. Patients aged ≥79 years with a CD score of ≥2 experienced a trend toward worse OS when treated with chemoradiation versus radiation alone (HR, 2.36; 

The HR was 0.93 for those aged ≥79 years treated with chemoradiation versus radiation alone (

 = .369). For those with a comorbidity score of ≥2, the HR was 1.00 between the two treatments (

 = .992). A benefit was also not experienced by patients with stage I/II tumors (HR, 1.09; 

Outside of patient characteristics, those treated with intensity modulated radiation therapy experienced an improvement in OS (HR, 0.76; 

 = .002). However, three-dimensional radiation was not associated with an OS benefit (HR, 1.02; 

The addition of chemotherapy to radiation is associated with increased toxicity; however, as radiation, chemotherapy, and supportive care techniques have improved, these adverse events have become more manageable. Unfortunately, this aspect could not be analyzed, as the NCDB does not provide clear-cut data for toxicity, Karam said.

“We found that patients who did get concurrent chemoradiation had a longer time to completion of radiation therapy, suggesting more treatment breaks. We couldn't look at aspiration pneumonia,” she said. “Despite treatment breaks, even after controlling for that, we found an overall survival advantage across subsites.”

Prior to the database analysis, studies had suggested that patients >70 years of age had worse survival outcomes with chemoradiation. In general, however, this elderly population represented just 4% of patients analyzed, which underpowered the data. Findings from the database study could be instrumental in changing the standard of care for elderly patients, specifically outside of the United States.

“The main takeaway is that you should not just look at the age of the patient,” said Karam. “In this day and age, when patients are healthier and living longer, give them the benefit of curative intent with the chemo.”

	Amini A, Jones B, McDermott J, et al. Does Age Matter? Survival Outcomes with the Addition of Concurrent Chemotherapy for Elderly Head and Neck Cancer Patients Undergoing Definitive Radiation Using the National Cancer Data Base. Presented at: 2016 Multidisciplinary Head and Neck Cancer Symposium; February 18-20, 2016; Scottsdale, AZ. Abstract 100.

View more from the Multidisciplinary Head and Neck Cancer Symposium

Concurrent chemoradiation significantly improved overall survival compared with radiation therapy alone for elderly patients with locally advanced head and neck cancers.

Chemoradiation Improves OS for Elderly Patients With Head and Neck Cancers

Ezra Cohen, MD, associate director, Moores Cancer Center,professor of Medicine, University of California, San Diego Health System, discusses tumor biomarker association with clinical outcomes in patients with recurrent and/or metastatic head and neck squamous cell carcinoma treated with afatinib versus methotrexate.

In a biomarker analysis of the LUX-Head and Neck 1 study, researchers sought to determine which patients, whether HPV-positive or HPV-negative, are more likely to benefit from treatment with afatinib versus methotrexate, which is the standard of care, Cohen explains.

In patients who were p16-negative, the response rate with afatinib was approximately 14%; there were almost no responses with methotrexate in this subgroup, Cohen says. Secondly, patients with 

 amplification had a higher benefit with afatinib. High levels of P10 and low levels of HER3 also served as biomarkers for patients who respond postiviely to afatinib, he adds.

Ezra Cohen, MD, associate director, Moores Cancer Center,
professor of Medicine, University of California, San Diego Health System, discusses tumor biomarker association with clinical outcomes in patients with recurrent and/or metastatic head and neck squamous cell carcinoma treated with afatinib versus methotrexate.

Dr. Cohen on Biomarkers Associated With Response in Patients With HNSCC Treated With Afatinib

Tobacco-associated mutations accumulate over time in smokers with HPV-positive oropharyngeal squamous cell cancer (OPSCC), resulting in less dependence on E6/E7 and other HPV-associated mutations, according to data presented at the 2016 Multidisciplinary Head and Neck Cancer Symposium.

The number of HPV viral reads was inversely associated with smoking and survival status.

“Patients who smoke and patients who were deceased from their cancer had a lower number of HPV viral reads,” said Jose P. Zevallos, MD, assistant professor and director of Oncologic Research in the division of Head and Neck Surgical Oncology at the University of North Carolina (UNC), Chapel Hill.

“This means that, potentially, the tumors began as HPV-driven, but over time developed subclones that were driven by tobacco-associated gene mutations as a result of exposure to smoking.”

The study used targeted next-generation sequencing analysis of over 800 genes in 66 cases of HPV-positive OPSCC. Patients were stratified by smoking status, either as >10 pack-years (40 patients) or <10 pack-years (26 patients). The patient data came from a North Carolina population-based epidemiological study that was conducted from 2001 to 2006. The mutations were measured against the Catalogue of Somatic Mutations (COSMIC), which is an online database of somatic mutation data that is maintained by the Sanger Institute as part of its Cancer Genome Project.

Zevallos explained that HPV-positive OPSCC, compared with HPV-negative OPSCC, has an excellent prognosis. However, among patients with HPV-positive OPSCC, smokers have a worse 5-year survival rate than never smokers.

This study sought to understand outcomes in patients with exposure to both HPV and tobacco. Previous work had shown that patients with exposure to both have an intermediate outcome relative to tumors that are HPV-negative and tobacco-driven versus never-smokers.

The mutational analysis found that heavy or ever smokers had tobacco-associated mutations that occurred almost exclusively in this group. The heavy smoking group had more 

mutations, which are related to inflammation. Mutations associated with tobacco exposure and poor survival had an almost exclusive occurrence in the heavy smoker group. These mutations included 

(6% in >10 pack-year smokers vs 0% in <10 pack-year smokers; 

The differences in gene mutations related to immunity and tobacco use may explain why smokers have more aggressive HPV-positive cancer, according to Zevallos.

Among the 66 patients, 95% had HPV 16 DNA, 3% had HPV 35, and 1% had HPV 58. The mean number of HPV reads per sample was 838,520. The number of reads varied by both survival and smoking status, with lower HPV reads associated with both worse survival and heavier smoking status.

The study concluded that the lower number of HPV reads associated with smoking and poor survival may suggest accumulation of tobacco-associated mutations. These mutations may lead to less dependency on E6/E7 and HPV-mediated oncogenesis. The authors hypothesized that the HPV-positive signature, perhaps from a PI3K pathway mutation as an initiating event, may be maintained as HPV-positive smokers acquire mutations in tobacco-related genes.

“This study will have important implications for personalizing treatment and decision making for HPV-positive oropharyngeal cancer, particularly in the era of less aggressive treatment for HPV-positive tumors with their excellent prognosis,” said Zevallos. “As opposed to deciding that 10 pack-years is a number that we use to define more aggressive disease, we are trying to define a molecular basis for more aggressive disease in order to decide who would benefit from less aggressive versus more aggressive treatment.”

Zevallos stated that tobacco-associated mutations are more detrimental than HPV-associated mutations. He added that adding tobacco to HPV worsens OPSCC outcomes.

A larger study of HPV-positive oropharyngeal cancer using DNA and RNA sequencing technologies is currently being conducted at UNC. Its goal is to define high-risk HPV-positive OPSCC.

Zevallos JP, Yim E, Brennan P, et al. Molecular profile of HPV-positive oropharyngeal squamous cell carcinoma stratified by smoking status. Presented at: 2016 Multidisciplinary Head and Neck Cancer Symposium; February 18-20, 2016; Scottsdale, AZ. Abstract 1.

Tobacco-associated mutations accumulate over time in smokers with HPV-positive oropharyngeal squamous cell cancer, resulting in less dependence on E6/E7 and other HPV-associated mutations.

Multidisciplinary Head and Neck Cancer Symposium | Conference

Dr. Seiwert on Immunotherapy in Head and Neck Cancer

Chemoradiation Improves OS for Elderly Patients With Head and Neck Cancers

Dr. Cohen on Biomarkers Associated With Response in Patients With HNSCC Treated With Afatinib

Smokers With HPV-Positive Oropharyngeal Cancer Accumulate Tobacco-Associated Mutations