A New Treatment Option for Head and Neck Cancer with Immunotherapy and Radiotherapy

The 2020 Multidisciplinary Head and Neck Cancers Symposium featured a new phase II clinical trial in which radiation therapy and pembrolizumab in combination, in patients with locally advanced head and neck squamous cell carcinoma were shown to produce better survival outcomes and acceptable side effects. This radiotherapy plus immunotherapy combination, cisplatin chemotherapy being unsuitable, may offer a new treatment option for such patients.

SUMMARY OF RESULTS

• The progression-free and overall survival rates at 1 year were 76% and 86%, respectively.
• P16-positive oropharyngeal cancer patients had progression-free and overall survival rates at 1 year of 88% and 94%, respectively; the rates for other patients were 58% and 75%.
• The exception, affecting 59% of patients, was grade 3-4 lymphopenia; otherwise, side effects were mild (grade 1-2).

Note: Immunotherapy for head and neck cancers had, until then, received approval only for stage 4 (advanced disease) from the FDA (see What is the best initial treatment for stage 4 or recurrent head and neck cancer). The oncology community had been awaiting results of immunotherapy given concurrently with radiotherapy in earlier-stage head and neck cancers, as in the study discussed in this article.

This single-arm clinical trial was specifically designed for patients who would normally receive platinum chemotherapy together with radiation but cannot tolerate its side effects, often because pre-existing hearing problems put them at risk of permanent hearing loss. Pre-existing kidney damage and nerve damage tend to be aggravated by cisplatin, putting patients at risk of permanent side effects.

Presenting the study, Dr. Jared Weiss explained, "This is a common dilemma because cisplatin, while effective, tends to be particularly toxic for patients and may lead to permanent side effects for some".

Summary of the Study

The single-arm study included 29 patients with locally advanced squamous cell head and neck cancer. Reasons for cisplatin ineligibility included otopathology (hearing problems in 69.0% of patients), nephropathy (kidney problems, 20.7%) and neuropathy (nerve damage, 6.9%).

Patients received three cycles of pembrolizumab with concurrent radiation therapy over 6 weeks, followed by three additional cycles of pembrolizumab.

At an average follow-up of 21 months, the progression-free and overall survival rates at 1 year were 76% and 86%. The estimated progression-free survival rate at 2 years was 71%, and the overall survival rate was 75%. In patients with P16-positive oropharyngeal cancer, progression-free and overall survival rates at 1 year were 88% and 94%, respectively; the rates for other patients were 58% and 75%.

Most side effects were mild (grade 1-2), except for grade 3-4 lymphopenia, which affected 59% of patients.

Dr. Weiss said, "This side effect profile is better than what patients generally experience with cisplatin and radiation". "Apart from the high rate of lymphopenia requiring additional intervention, it was more consistent with what we see from radiation therapy alone."

This study is among the first to show that immunotherapy drugs in the PD-1 inhibitor class are also effective at earlier stages.

Conclusion

There is compelling evidence that radiation sensitizes patients to immunotherapy and may enhance its effects. The reverse also appears to be true: for radiation therapy to work, a functional immune system is required, and our hope is that pembrolizumab may act as a radiosensitizer for these patients.

Concurrent pembrolizumab and radiotherapy demonstrated good progression-free and overall survival in locally advanced squamous cell head and neck cancer, with a favorable side effect profile, regardless of p16 status or anatomical location, and warrants a more extensive clinical trial.