Source: Medscape.com
Author: Nick Mulcahy
Date: September 27, 2017

SAN DIEGO, California ― Daniel Ma, MD, of the Mayo Clinic in Rochester, Minnesota, treats a lot of relatively young patients with human papillomavirus (HPV)-related oropharyngeal cancers who are cured by various standard combinations of surgery, radiation therapy and chemotherapy and then have “another 30 to 40 years of life ahead of them.”

But that life expectancy can be marred by the “potentially life-altering side effects” of standard treatment, including dry mouth, loss of taste, and, in about one half of patients, difficulty swallowing, he said.
These patients inspired the genesis of Dr. Ma’s phase 2 study of an “aggressive dose de-escalation” of adjuvant radiation in this setting, he said.

The investigators evaluated experimental radiation doses of 30 to 36 Gy, which is a 50% reduction from the current standard of 60 to 66 Gy.

At a median of 2 years’ follow-up among 80 patients, the treatment de-escalation has resulted in locoregional control rates comparable to historical controls, low toxicity, and, perhaps most notably, no decrement in swallowing function or quality of life, Dr. Ma reported here at the American Society for Radiation Oncology (ASTRO) 2016 Annual Meeting.

The toxicity and swallowing results are “the most exciting data,” Dr. Ma told a standing-room-only crowd at a meeting session today.

“It’s the first clinical trial in head and neck cancer to demonstrate no injury to swallowing function after radiation,” he told Medscape Medical News. In other words, patients’ ability to swallow was no worse post treatment. In fact, patients’ ability to swallow improved slightly at 1 year following radiation therapy compared to pretreatment (P = .03).

“It’s an exciting concept. Everyone’s going to want to hear more about it,” said Thomas Galloway, MD, of Fox Chase Cancer Center in Philadelphia, Pennsylvania, who was asked for comment about the trial.

The answer is not yet known, but the 2-year results from Dr. Ma are encouraging.

Two-year data indicate that after de-escalated treatment, the rate of locoregional tumor control was 95%, which is comparable to results with standard radiation (60 Gy) from the Radiation Therapy Oncology Group (RTOG) 0234 trial.

In the Mayo Clinic trial, three patients experienced local recurrence, and one patient experienced a nodal recurrence.

Fox Chase’s Dr. Galloway also observed that, in the new trial, patients received 30 Gy delivered in 1.5 Gy twice a day over 12 days (along with weekly docetaxel, 15 mg/m2, days 1 and 8). Twelve days is a lot shorter than the standard 6 weeks for 60-Gy therapy, but the twice-daily schedule may not be suitable for all patients, he pointed out.

De-escalation radiation therapy is experimental, but a phase 3 study that seeks to confirm the approach, known as the DART-HPV trial, is now underway.

“This is not incremental change,” he told Medscape Medical News. “It’s a stark change from the current standard of care.”

Dr. Galloway and Dr. Ma both said that HPV-positive head and neck cancers are necessitating change, because patients with these cancers are younger and healthier than patients without the virus, whose cancers are typically caused by smoking and alcohol consumption.

Some HPV-positive patients are now being treated without surgery. “What the perfect recipe for treatment is, no one knows for sure,” Dr. Galloway told Medscape Medical News about treatment combinations.

Paul Harari, MD, of the University of Wisconsin, Madison, said the HPV-positive head and neck cancers, including oropharyngeal cancers, “warrant different treatment approaches.” Standard treatment is toxic ― “make no mistake about it,” Dr Harari commented while acting as moderator at a press conference featuring the dose de-escalation trial.

However, cutting the radiation therapy dosage, he said, prompts a “tense question: can you maintain the cure rate?”

 

More Study Details, Including Toxicity

About half of the study patients, all of whom had oropharynx squamous cell carcinoma, had the above-described 2-week-long treatment schedule. But 43 patients had extracapsular extension, a marker of aggressive disease, and thus received an additional radiation boost to the affected areas, for a total dose of 36 Gy.

Data for both groups of patients were combined in the statistical tallies.

All of the study patients had no evidence of residual disease following surgery and a minimal smoking history (eg, less than one pack per day for 10 years or less). The median patient age was 60.5 years. All patients had stage III or IV disease.

There was also a “very dramatic reduction” in side effects, compared with standard treatment, said Dr. Ma. No patients required percutaneous endoscopic gastrostomy (PEG); by contrast, with traditional radiation therapy, one fifth to one third of patients undergo PEG.

The PEG feeding tube is inserted through the abdomen into the stomach. Typically, one fifth to one third of patients will receive such a feeding tube during standard treatment for oropharyngeal cancers, he said.

The rate of grade ≥2 toxicities 2 years post radiation therapy was 10%. Again, this compared favorably with 55% rate reported in RTOG 0234.

No patients had grade 3+ toxicity at 1 or 2 years following treatment.

All 14 patients (18%) who experienced cumulative grade 3+ toxicity did so within 3 months of treatment, and all cases resolved by 6 months post treatment. One patient experienced acute grade 4 toxicity related to a chemotherapy reaction, which quickly resolved.

Patient quality of life either improved or did not change following treatment, except with regard to xerostomia. Patients reported worse salivary flow following treatment (P < .0001).

Dr. Ma, his coinvestigators, Dr Galloway, and Dr. Harari have disclosed no relevant financial relationships.

American Society for Radiation Oncology (ASTRO) 2017 Annual Meeting. Abstract LBA-14, presented September 26, 2017.