Two new exploratory studies of radioenhancers used in combination with radiation therapy in the treatment of head and neck cancers showed that these agents can boost the effectiveness of radiotherapy in these cancers.

The two phase 2 studies, presented at the 2024 American Society for Radiation Oncology (ASTRO) Head and Neck Cancer Symposium on March 1, 2024, found an increase in 1-year local control rate, progression-free survival, and overall survival.

In one study, which explored the use of the hedgehog pathway inhibitor vismodegib alongside radiation therapy, researchers found that all but one patient with locally advanced, unresectable basal cell carcinoma (BCC) demonstrated 1-year local control — a significantly better rate than that expected from radiation alone — and 83% were alive at 5 years.

The second, which explored the use of hafnium oxide nanoparticles (NBTXR3) prior to radiation therapy, also reported promising results. Patients with T3/4 locally advanced head and neck squamous cell carcinoma of the oropharynx or oral cavity who were ineligible for chemoradiation demonstrated a median overall survival of 18.1 months vs 12 months, the life expectancy with radiation alone.

Although small, both studies suggest a role for radioenhancers in head and neck cancer, Jonathan Schoenfeld, MD, a head and neck cancer radiation oncologist at the Dana Farber Cancer Institute, in Boston, Massachusetts, told Medscape Medical News.

Evidence for Vismodegib

Vismodegib, which has been on the US market since 2012, was approved for metastatic BCC or BCC that cannot be treated with radiation or surgery, but it is not approved for use with radiation. Still, case reports have demonstrated that the radioenhancer alongside radiotherapy can improve BCC outcomes.

In the new study, investigators augmented standard-of-care radiation with the vismodegib in 24 patients with locally advanced, unresectable BCC. These patients were treated with 12 weeks of vismodegib at 150 mg daily, followed by an additional 7 weeks of vismodegib concurrently with 50-70 Gy radiotherapy in 25-35 fractions.

Five patients, however, were unable to complete vismodegib induction mostly due to adverse events and withdrew from the study.

Among the remaining 19 patients, the 1-year local control rate was 91% with the addition of vismodegib vs an expected rate of 60% with radiation alone. Five-year progression-free survival was 78%, and 5-year overall survival was 83%. Treatment was also associated with improvements in quality of life.

The most common adverse events in the study were dysgeusia, fatigue, and myalgia. There were no grade 4/5 events and no distant metastases or BCC-related deaths.

Given the results, the combination approach is now routine at Memorial Sloan Kettering Cancer Center (MSKCC), in New York City, and the University of California, San Francisco, where the subjects were treated.

In a meeting news summary from ASTRO, Nancy Lee, MD, an MSKCC radiation oncologist who was not involved in the work, called the results “remarkable” and said they could set “a new standard” of care for locally advanced, unresectable BCC.

The current study fulfills the need for prospective data on the combination, said Barker. It also might be the best evidence the head and neck community will get.

A phase 3 trial is unlikely because locally advanced, unresectable BCC is rare and a trial would take too long, he noted. Plus, vismodegib only has a few years left on its patent.

Nanoparticles as Radioenhancers

The other radioenhancer study explored the use of NBTXR3 in patients with T3/4 locally advanced head and neck squamous cell carcinoma of the oropharynx or oral cavity — an indication the US Food and Drug Administration has granted fast-track status.

NBTXR3 is currently approved in Europe for soft tissue sarcoma radiotherapy and sold under the brand name Hensify.

The current study focused on the primary tumors of 56 patients with locally advanced head and neck squamous cell carcinoma of the oropharynx or oral cavity who were too old or frail for cisplatin chemotherapy.

These patients received an intravenous aqueous suspension of the nanoparticles at a dose equivalent to 22% of the baseline tumor volume, for a median dose of 13.6 mL. Patients then had 70 Gy of intensity-modulated radiation in 35 fractions.

The nanoparticles increase absorption of the radiation, lead investigator Christophe Le Tourneau, MD, PhD, a medical oncologist at the Institut Curie, Paris, France, explained.

Overall, median overall survival was 18.1 months — a 6-month improvement compared with what’s observed in people who receive radiation alone — and median progression-free survival was 11.4 months. Among 36 participants with a partial or complete response, median overall survival was 42.8 months.

Six patients (11%) had grade 3 or worse reactions to the nanoparticles, including stomatitis, tumor pain, decreased lymphocytes, sepsis, and tumor hemorrhage. Radiation also played a role in some of the effects.

The injections took a median of 11 minutes and were associated with grade 3 or higher reactions in three participants (5%), including tumor pain, hypertension, swollen tongue, and oxygen desaturation.

The results support an ongoing phase 3 trial, NANORAY-312, pitting NBTXR3-enhanced radiation against standard radiation plus/minus cetuximab for platinum-ineligible LA-HNSCC, said Le Tourneau.

The approach is promising and should certainly be explored in other settings if the phase 3 NANORAY trial is positive, Schoenfeld, the Dana Farber radiation oncologist, told Medscape Medical News.

He cautioned, however, that 14 oropharyngeal subjects in Le Tourneau’s study had HPV/P16-positive tumors that tend to do well even with conventional treatment.

The NBTXR3 study was funded by the product’s maker, Nanobiotix. Le Tourneau reported travel expenses and advisor fees from the company. Funding for the vismodegib study was not reported. Barker reported ties to Amgen, Merck, Genzyme, and other companies, but no ties to vismodegib maker Genentech/Roche. Schoenfeld reported research funding/payments from Genentech and other companies. Lee didn’t have any disclosures.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected]