Source: www.medpagetoday.com
Author: Ian Ingram, Deputy Managing Editor, MedPage

In 2019, headlines in head and neck cancer were dominated by a new first-line approval in squamous cell carcinoma (SCC), further attempts at treatment deintensification in the lower-risk human papillomavirus (HPV) population, and a provocative trial looking at patients’ quality of life following either robotic surgery or radiation.

Immunotherapy OK’d in First-line
Based on data from the three-arm KEYNOTE-048 trial, the FDA approved pembrolizumab (Keytruda) for the first-line treatment of metastatic or unresectable recurrent head and neck SCC. The PD-1 immune checkpoint inhibitor was approved in combination with chemotherapy for all patients, or as monotherapy for those with PD-L1 expression.

Final results of the study demonstrated a 23% reduction in the hazard for death for the group treated with pembrolizumab plus platinum chemotherapy (cisplatin or carboplatin) and 5-fluorouracil. This group had a median overall survival of 13.0 months, as compared with 10.7 months for those treated with the EXTREME regimen of platinum chemotherapy plus 5-fluorouracil and cetuximab (Erbitux).

A pembrolizumab monotherapy arm of KEYNOTE-048 showed non-inferiority to EXTREME in all comers and superiority in patients with a PD-L1 combined positive score (CPS) ≥1, as represented by a 22% reduction in the hazard for death over the study period. In this CPS ≥1 population, which made up about 85% of the study population, median overall survival was 12.3 with pembrolizumab alone versus 10.3 months with EXTREME.

ORATOR Trial Upends Assumption of Surgical Superiority
In the first randomized trial to pit transoral robotic surgery (TORS) against radiotherapy for patients with oropharyngeal SCC, the ability to swallow and other outcomes appeared to be better with radiation — contradicting previous retrospective data that favored surgery.

With roughly 2 years of follow-up, the phase II trial of 68 patients met its primary endpoint, showing a statistically significant improvement in swallowing 1 year after treatment in the radiotherapy group.

This group had a nearly 7-point advantage on the 100-point MD Anderson Dysphagia Inventory (MDADI) scale compared with the surgery cohort (86.9 vs 80.1, respectively, P=0.042), suggesting that these patients may have improved swallowing function — the trial had prespecified that a 10-point difference would be considered “clinically meaningful.”

Investigators said the findings indicate that patients should be offered both treatment options.

Less Therapy in HPV-Positive Disease
At the American Society for Radiation Oncology (ASTRO) annual meeting, results from the HN002 trial showed impressive results with two de-escalation strategies in low-risk HPV-positive head and neck cancer. Among the 306 mostly non-smoking patients in the phase II multi-institutional study, those assigned to lower-dose (60 Gy) intensity-modulated radiotherapy (IMRT) plus weekly cisplatin had a 2-year progression-free survival (PFS) of 90.5%, as compared with 87.6% in a group treated with IMRT at 60 Gy alone.

Only the combination arm met the investigators’ prespecified PFS target, while both met their swallowing-related quality-of-life criteria. On the MDADI scale, patients reported scores of 85.3 (5.6-point decline from baseline) in the combined modality arm and 81.8 (6.2-point decline) in the radiation-alone arm. Overall survival (OS) rates at 2 years were greater than 95% for the two arms.

Meanwhile, a prospective study from the University of North Carolina reported 2-year rates of locoregional control and OS of 95% with a dual strategy of deintensified treatment for HPV-positive oropharyngeal cancer.

PFS at 2 years was 86%, and 91% of the 114 patients remained free of distant metastases. No grade ≥3 late adverse events occurred, and global quality of life improved from pretreatment to 2 years.

Experts emphasized, however, that deintensification should only be attempted in clinical trials

“What is the best treatment for patients with low-risk oropharynx cancer?” said ASTRO discussant Beth Beadle, MD, of Stanford University Medical Center in California, in discussing the HN002 trial. “Standard of care is standard of care, we do not have phase III data supporting de-escalation off protocol.”

Standard of care remains 70 Gy with concurrent cisplatin for patients with low-risk disease.

Retrospective Studies Provoke
A single-arm trial in New York reported that a treatment delay greater than 2 months from diagnosis was significantly associated with worse OS in patients with head and neck SCC.

In a group of 956 patients treated at an urban academic center, those with a time to treatment initiation (TTI) longer than 60 days were significantly more likely to die from their disease (odds ratio [OR] 1.69, 95% CI 1.32-2.18) and have disease recurrence (OR 1.77, 95% CI 1.07-2.93) compared to those treated within this timeframe. The 5-year overall survival for patients dropped from 64.5% to 47.0% when the TTI stretched beyond 60 days.

“If I invented a drug that could give a 20% improved survival in head and neck cancer patients, a disease where survival has not changed for many years, I would probably be getting handed a large amount of funding,” study author Vikas Mehta, MD, MPH, of Montefiore Medical Center in New York City, told MedPage Today.

“This study is just as important,” he continued. “Getting patients to treatment in a timely manner can independently improve survival.”

Another retrospective study pointed to the possible benefit of regular use of aspirin or other common nonsteroidal anti-inflammatory drugs (NSAIDs) for head and neck cancers with a particular gene mutation.

In 75 patients with PIK3CA mutations or amplification, users of NSAIDs for at least 6 months after curative treatment had significantly prolonged disease-specific survival (HR 0.23, 95% CI 0.09-0.62) and OS (HR 0.31, 95% CI 0.14-0.69) compared with non-regular NSAID users. The effect was seen regardless of patients’ HPV status. Predicted 5-year OS rates were 78% for the regular NSAID users and 45% for non-regular users.

Is Magic Mouthwash Just an Illusion?
Two medicated mouthwashes led to reductions in oral mucositis pain for head and neck cancer patients treated with radiotherapy, but not at a level deemed clinically important, a randomized phase III study found.

Within 4 hours of radiotherapy, pain from oral mucositis dropped by 11.7 points (as defined by the area under the curve) with a diphenhydramine-lidocaine-antacid rinse — or “magic mouthwash” — and 11.6 points with a doxepin mouthwash, compared with 8.7 points with placebo, researchers reported.

Compared with placebo, diphenhydramine-lidocaine-antacid led to a 3.0-point improvement (95% CI 0.1-5.9) while the doxepin mouthwash led to a 2.9-point improvement, both of which were less than what the investigators said would be clinically important differences going into the trial.

“These data tell us that magic mouthwash (or doxepin) is not the sole answer to managing mucositis — physicians should not prescribe magic mouthwash and expect magic!” Arjun Gupta, MD, of the Sidney Kimmel Comprehensive Cancer Center in Baltimore, who was not involved in the study, told MedPage Today.

“Most providers do not know the contents or concentrations of the ingredients in these mixed-medication formulations,” he said. “They could also contain unnecessary and harmful ingredients such as steroids and antibacterials/antifungals. How many other drugs do physicians prescribe without knowing the contents or concentration?”