Allison Wright

DOS 741
Protocol Project - Paper Summary

My project will be focusing on the clinical trial NRG-HN005. This protocol is a head and
neck study with an emphasis on HPV positive, early-staged patients with non-smoking squamous
cell carcinoma of the oropharynx. HN005 has a main requirement that the patient is to have a
smoking history of 10 or less years and a p16 positive immunohistochemistry. This means that
the nuclear and cytoplasmic staining is strong and diffuse. Some factors that will consider a
patient ineligible include staging T0 or T4 with zero or bilateral nodal involvement, metastatic
disease below the clavicles, previous treatment in the same area less than three years prior,
severe hypersensitivity to monoclonal antibodies or cisplatin, pregnant, and hoping to bear or
father children.
This study came to fruition after the results from two other studies were published. These
studies were NRG-HN002 and RTOG 1016. The standard of care for oropharyngeal cancer with
concurrent platinum-based chemotherapy with curative intent has been established as 70 Gy. It
has been found that high dose radiation therapy, such as treatments going to 70 Gy, induce
dysphagia which decreases patient quality of life. RTOG 0129 did a study with HPV-positive
patients with a smoking history of 10 or less years and found results to be 3-year rates of overall
survival at 93% in low risk patients. HN002 conducted a study with 60 Gy to the gross disease,
48-54 Gy to the elective neck, and 30 mg/m2 per week. RTOG 1016 compared concurrent
cisplatin and concurrent cetuximab with 70 Gy radiation therapy over 6 weeks. In this study,
chemo was administered at 100 mg/m2 for 2 cycles every 3 weeks. These studies resulted in the
HN005 trial where RTOG 1016 is used as the control arm; there are two phases of comparison
with 2 or 3 arms for each phase. The main difference between HN002 and HN005 is that HN005
uses nivolumab instead of cetuximab in arms 2 and/or 3.
The main purpose of the study is to hope that HN005 finds an equivalent or better
treatment protocol to the current standard of care. The reason that these studies are performing
trials with different radiation doses is to find what dose (60 Gy or 70 Gy) in combination with
which chemotherapy drugs is best at killing the tumor, while maintaining quality of life, and
allowing the patient to live without disease for as long as possible.