May 30, 2014.

2014 Annual Meeting of the American Society of Clinical Oncology (ASCO): Abstract LBA6006.

CHICAGO — Oropharyngeal cancer patients who test positive for human papillomavirus (HPV) could be treated with lower than standard doses of radiation, which reduces the risk for adverse effects, suggest results from a phase 2 study.

Patients were first treated with induction chemotherapy, and the results suggest that those who respond can safely forgo standard radiation therapy in favor of a lower dose with fewer adverse effects, according to results from the ECOG 1308 study.

This “chemoselection” can guide radiotherapy treatment strategies aimed at lowering acute and late toxicities,” researcher Anthony Cmelak, MD, professor of radiation oncology at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, told Medscape Medical News.

This story was vetted for accuracy by the Oral Cancer Foundation scientific review staff

“The lower dose allows patients to avoid long-term dysphagia, fibrosis, xerostomia, dental problems, strictures, or long-term percutaneous endoscopic gastrostomy tubes,” Dr. Cmelak commented. “The risks of these types of complications escalate rapidly after 54 Gy intensity-modulated radiation therapy (IMRT), and become the most commonly seen long-term problems in patients when treated to the standard dose of 70 Gy.”

The study, highlighted during a press briefing here at the 2014 Annual Meeting of the American Society of Clinical Oncology® (ASCO), included 90 patients with stage III/IV HPV-positive oropharyngeal squamous carcinoma who received induction chemotherapy with paclitaxel, cisplatin, and cetuximab.

Based on having a complete clinical response to chemotherapy, meaning no signs of cancer on endoscopic exam, 62 patients were selected to receive a reduced (54 Gy) dose of IMRT, while the rest received the standard dose of 70 Gy.

At two years, overall and progression-free survival was better in the low-dose group (93% and 80% respectively) compared to the high-dose group (87% and 65% respectively), especially among minimal smokers (less than 10 pack years) who had early stage disease (96% for both).

Dr. Cmelak said despite the favorable results with chemoselection for reduced radiation dose, it would be premature to translate this into clinical practice. There has been a lot of discussion among head and neck cancer specialists about reducing the aggressiveness of treatment for patients with HPV-positive disease, because they have a better prognosis than HPV-negative patients, but at the same time there is a concern that this does not result in under treatment, he commented.

“I don’t recommend using lower doses of radiation now for these patients off-study.

Ultimately it will take a large randomized trial looking at standard approaches…and comparing those to a deintensified regimen based on response rates up-front, to safely ensure that we’re not going to be jeopardizing patient survival in order to minimize toxicity,” he said.

The study results represent “great progress”, said Gregory Masters, MD, ASCO’s expert on head and neck cancers, and director of medical oncology at the Helen F. Graham Cancer Center. “Most of what we’ve been doing in oncology is escalating doses and treatment and that’s not necessarily always the right answer. As we try to treat with more precision…this is a step in the right direction but I don’t think anyone would say we’re at the point where we know exactly how to modify the doses for HPV-positive cancer.”

“It is laudable to see a trial addressing a means of separating a disease into two populations, one favorable based on response that may be treated with a lower radiotherapy…and the other a potentially more adverse group with less response justifying continuation with more conventional doses of radiotherapy,” Brian O’Sullivan, MD, told Medscape Medical News.

Dr. Sullivan, an expert in head and neck cancer and professor in the Department of Radiation Oncology at the University of Toronto, recently published a paper on the nuances of de-intensifying therapy in HPV-positive oropharyngeal cancer, reported by Medscape Medical News.

He said the ECOG 1308 study “was designed in the era before there was the same appreciation of the stratification of risk in this disease,” and more recent trials take into account risk of distant metastasis, “which has emerged as one of the leading causes of death in this patient population,” to allow an even more precise stratification of risk in HPV-positive disease.

In the future, “trials should probably be designed with this in mind, potentially using the strategy illustrated by ECOG 1308 that employs an induction systemic approach emphasizing agents capable of addressing distant metastases and potentially using a less intense local treatment approach in those who respond,” he said.

The study was funded by the National Institutes of Health. Anthony Cmelak reports financial relationships with Bristol-Myers Squibb. Dr. O’Sullivan and Dr. Masters have disclosed no relevant financial relationships.