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2018 ASTRO: Combined Radiation and Cisplatin in HPV-Related Head and Neck Cancer

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Key Points

  • Cetuximab with radiation was associated with inferior overall survival and progression-free survival compared to the cisplatin/radiation treatment combination, with 5-year estimates of 78.4% for cisplatin and 67.3% for cetuximab.
  • Estimated 5-year locoregional failure/distant metastasis rates were also considerably lower with radiation plus cisplatin (9.9% and 8.6%, respectively) than with radiation plus cetuximab (17.3% and 11.7%, respectively).
  • The estimated 5-year survival rate was higher (84.6%) in the cisplatin group compared to the cetuximab group (77.9%).

A phase III trial has determined that cisplatin chemotherapy combined with radiation therapy showed high amounts of activity in human papillomavirus (HPV)-related head and neck cancer. Findings from NRG-RTOG 1016 were presented by Trotti et al the 60th Annual Meeting of the American Society for Radiation Oncology (ASTRO) (Abstract LBA4).

“We’ve now established that high-dose cisplatin chemotherapy in combination with radiation is the standard of care for HPV-related oral cancers,” said first author and trial co-lead investigator Andy Trotti, MD, a radiation oncologist at the Moffitt Cancer Center, in a statement. “Prior to this study, there were no definitive, ‘state of the art’ trials in this specific cancer population.”

A similar study was presented at the recent European Society for Medical Oncology (ESMO) 2018 Congress by Mehanna et al.

Dr. Trotti and his colleagues aimed to explore whether the combination of cetuximab (Erbitux) and radiation therapy would be less toxic to patients than treatment combining radiation with cisplatin—without lowering survival rates. “We had hypothesized that survival with cetuximab might be very close (within 5%) to that of cisplatin,” said Dr. Trotti, “but that was not the case.”

Study Methods and Findings

In this phase III trial, 805 patients with locoregionally advanced HPV-related oropharynx cancer were randomly assigned (1:1) to two cycles of cisplatin chemotherapy (100 mg/m2) every 3 weeks plus radiation therapy, or the same radiation therapy with weekly cetuximab treatments. Overall, 90% of the patients were men, with a median age of 58.

The results were released early when an interim data analysis found cetuximab with radiation was associated with inferior overall survival (hazard ratio [HR] = 1.45, 95% confidence interval [CI] = 1.03–2.05) and progression-free survival (HR = 1.72, 95% CI = 1.29–2.29), compared to the cisplatin/radiation treatment combination, with 5-year estimates of 78.4% (95% CI = 73.8%–83.0%) for cisplatin and 67.3% (95% CI = 62.4%–72.2%) for cetuximab.

Estimated 5-year locoregional failure/distant metastasis rates were also considerably lower with radiation plus cisplatin (9.9% and 8.6%, respectively) than with radiation plus cetuximab (17.3% and 11.7%, respectively). The estimated 5-year survival rate was higher (84.6%) in the cisplatin group compared to the cetuximab group (77.9%).

Adverse Events

Using traditional toxicity reporting methods, researchers found that patients receiving cisplatin experienced slightly more serious (grade 3–5) side effects (82%) than those treated with cetuximab (77%). However, said Dr. Trotti, traditional reporting of overall adverse event rates tends to obscure important differences in the magnitude of the toxicity profiles. “That is where our new metric, ‘T score,’ does a better job of capturing the frequency of high-grade events, or toxicity burden,” he said.

Using the T-score system, all high-grade events experienced by the entire group are divided by the total number of patients. A T score of 2.35 means the average patient had more than 2 high-grade events, whereas traditional reporting would only reflect 1 event per patient. T-score analysis showed a 40% higher rate of high-grade events for cisplatin, compared to a nominal 5-point difference (82% vs 77%) with the traditional reporting method.

The specific profile of adverse effects varied by agent, with anemia, hearing loss, nausea, vomiting, neutropenia, and kidney injury more common with cisplatin, whereas rashes were more common among those treated with cetuximab. The rate of long-term, severe dysphagia was 4% for patients treated with cisplatin compared to 6% for patients treated with cetuximab. Quality-of-life measures were collected but have not yet been reported.

Other Uses of Cetuximab

Cetuximab may still be considered a viable treatment option for patients who cannot tolerate cisplatin, such as those with significant hearing loss or severe diabetes-related neuropathy, said Dr. Trotti. Those conditions may be exacerbated by treatment with cisplatin.

“You want to avoid worsening patients’ hearing conditions or nerve damage,” he said. “These patients need alternative medications, such as cetuximab, which do not have overlapping toxicity with neuropathy or hearing loss.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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