PracticeUpdate Oncology Best of 2018

ASTRO 2018 35

Radiation + Cisplatin Established as Standard of Care for HPV- Related Head and Neck Cancer Patients treated with radiation + cisplatin survived longer and experienced a lower rate of metastasis than those who received radiation + cetuximab. C isplatin + radiation therapy has been found to produce better results than cetuximab + radiation therapy and

should be considered the standard of care for human papillomavirus (HPV)-related head and neck cancer. This finding of the randomized, phase III NRG Oncology/Radiation Therapy Oncol- ogy Group 1016 trial was reported at ASTRO 2018. Andy Trotti, MD, of theMoffitt Cancer Center in Tampa, Florida, explained that the combi- nation of high-dose cisplatin chemotherapy and radiation has now been established as the standard of care for HPV-related oral cancer. Previously, there were no definitive trials in this cancer population. Survival rates are high. Mortality risk is 50% lower among patients with HPV-associated oropharyngeal squamous cell cancer than among those with HPV-negative disease, partly because patients tend to be younger and healthier at diagnosis. Serious adverse side effects from treatment are frequent, however. Dr. Trotti and colleagues set out to determine whether cetuximab + radi- ation would be less toxic than cisplatin + radiation, without lowering survival rates. According to Dr. Trotti, survival with cetux- imab was hypothesized to be within 5% of that with cisplatin; however, this was not demonstrated. A total of 805 patients with locoregionally advanced HPV-related oropharyngeal can- cer were randomized 1:1 to two cycles of cisplatin chemotherapy (100 mg per m 2 of body surface area) every 3 weeks + radia- tion therapy, or the same radiation therapy with weekly cetuximab treatments. Overall, 90% of patients were men whose median age was 58 years. Results were released early when an interim data analysis found that cetuximab + radiation was associated with inferior over- all survival (HR 1.45; 95% CI 1.03–2.05) and progression-free survival (HR 1.72; 95% CI 1.29–2.29) versus cisplatin + radiation, with 5-year estimates of 78.4% (95% CI 73.8% to 83.0%) for cisplatin and 67.3% (95% CI 62.4% to 72.2%) for cetuximab. Estimated 5-year locoregional failure/ distant metastases rates were also con- siderably lower with radiation plus cisplatin (9.9%/8.6%) than with radiation + cetuximab

©ASTRO 2018

(17.3%/11.7%). The estimated 5-year survival rate was substantially better (84.6%) in the cisplatin than in the cetuximab group (77.9%). Using traditional methods of reporting toxicity, patients receiving cisplatin expe- rienced slightly more serious (grade 3–5) side effects (82%) overall than those treated with cetuximab (77%). Traditional report- ing of overall adverse event rates tends to obscure important differences in the magnitude of toxicity profiles. According to Dr. Trotti, the new T score effectively cap- tures the frequency of high-grade events. 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 two high-grade events. Tra- ditional reporting would reflect only one event per patient. T score analysis showed a 40% higher rate of high-grade events for cisplatin versus a nominal five-point dif- ference (82% vs 77%) with the traditional reporting method. The specific profile of adverse effects var- ied by agent, with anemia, hearing loss, nausea, vomiting, neutropenia, and kidney injury more common with cisplatin. Rashes were more common among those treated with cetuximab. The rate of long-term, severe dysphagia (difficulty swallow- ing) was 4% for cisplatin versus 6% for

cetuximab. Quality of life measures were collected but have not been reported yet. Based on promising preliminary trial results that compared cetuximab versus radia- tion alone, some physicians had adopted cetuximab as a standard of care substitute for cisplatin, as a first-line option in other- wise healthy patients. 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. Cisplatin may exacerbate those conditions. Dr. Trotti explained that worsening nerve damage or hearing conditions should be avoided in patients. In these cases, cetux- imab or other alternative medications that do not have overlapping neuropathy or auditory toxicity should be used. www.practiceupdate.com/c/75216 " 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. "

VOL. 2 • NO. 4 • 2018