News and Publications

Radiation/immunotherapy combination shows promise for recurrent/metastatic HNSCC

SCOTTSDALE, Az., February 27, 2020

A new phase II trial finds that a combination of radiation therapy and immunotherapy led to encouraging survival outcomes and acceptable toxicity for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). The combination of radiation and pembrolizumab may offer a new treatment option for patients who are ineligible for cisplatin chemotherapy, part of standard treatment for the disease. Findings will be presented at the 2020 Multidisciplinary Head and Neck Cancers Symposium, taking place February 27-29 in Scottsdale, Arizona.

The single-arm trial was designed specifically for patients who normally would receive platinum chemotherapy together with radiation but may not be able to tolerate its side effects, most often due to preexisting hearing problems that place patients at risk of permanent hearing loss. Preexisting kidney damage and nerve damage also tend to be aggravated by cisplatin and place patients at risk for permanent side effects.

"That is a common dilemma in the exam room because cisplatin, while effective, tends to be particularly toxic for patients and can lead to permanent side effects for some," explained lead author Jared Weiss, MD, an associate professor of medicine at the University of North Carolina Lineberger Comprehensive Cancer Center. "I will have patients I want to treat with platinum chemotherapy, but I also want to align treatment with their values. Is the patient willing to accept a risk of deafness or exacerbated ringing in their ears? These are not acceptable consequences for most people."

The single-arm trial included 29 patients with locally advanced HNSCC. All patients would have ideally received cisplatin with their radiation but were ineligible for platinum chemotherapy. Patients were treated with three cycles of pembrolizumab and concurrent radiation therapy over six weeks, followed by three additional cycles of the immunotherapy drug.

With a median follow-up of 21 months, the rates of one-year progression-free and overall survival were 76% [95% CI 56-88] and 86% [67-95], respectively. Estimated two-year PFS was 71% [49-84] and estimated two-year OS was 75% [51-88]. For patients with p16+ oropharynx cancer, the one-year PFS and OS rates were 88% and 94%, respectively; for the other patients, the rates were 58% and 75%, respectively.

Most toxicities were mild (grade 1-2) with the exception of grade 3-4 lymphopenia, which affected 59% of patients. "This toxicity profile is better than what patients generally experience with cisplatin and radiation," explained Dr. Weiss. "It was more consistent with what we see from radiation therapy alone, with the exception of a high rate of lymphopenia that warrants additional study."

While engaging PD-1/PD-L1 blockade following chemoradiotherapy has improved survival in lung cancer, this trial is one of the first to show its potential efficacy for head and neck cancers. "There are convincing arguments that radiation sensitizes patients to immunotherapy and can enhance its effects. And the opposite direction also seems to be true – radiation therapy needs a functional immune system to work, and our hope was that pembrolizumab might be a radiation sensitizer for these patients," said Dr. Weiss.

Additionally, unlike chemoradiation therapy, the combination of radiation and pembrolizumab pairs two active modalities that can be curative by themselves. "If you look back to the historic studies, radiation alone often cures patients with this disease.Some of the first patients treated with pembrolizumab for recurrent/metastatic cancer are still alive many years out, with no evidence of disease," said Dr. Weiss. "And so, our concept was that, in addition to whatever synergy the immunotherapy might provide with radiation, we also conceived of it in a more straightforward way as a 'second shot on goal' toward cure."

Dr. Weiss cautioned that findings need confirmation in a randomized trial before the combination is recommended to patients.

Dr. Weiss will present "Progression-free survival, overall survival and immunophenotyping outcomes for patients with stage III-IV head and neck cancer and cisplatin contraindication treated with definitive radiotherapy plus pembrolizumab" tomorrow during the symposium's Oral Abstract Session. The study was funded by Merck. Email press@astro.org for a copy of the abstract or presentation slides from the meeting.

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Attribution to the 2020 Multidisciplinary Head and Neck Cancers Symposium requested in all coverage. This release includes updated information not available in the abstract.

2020 Head and Neck Cancers Symposium News Planning Team
Robert L. Ferris, MD, PhD; Maie St. John, MD, PhD; Francis P. Worden, MD; Charu Aggarwal, MD, MPH; Sue Yom, MD, PhD; Brian O'Sullivan, MD, FASTRO; disclosures available online.

ABOUT THE SYMPOSIUM
The 2020 Multidisciplinary Head and Neck Cancers Symposium is a two-and-a-half-day meeting that convenes radiation oncologists, medical oncologists, surgeons and all members of the treatment team for a practical and comprehensive examination of treatment advances for patients with head and neck cancers. Scientific, interactive and case-based educational sessions will cover the latest research on multidisciplinary therapies, clinical applications and new treatment strategies, supportive care and toxicity mitigation. The meeting is cosponsored by the American Society for Radiation Oncology (ASTRO), the American Society of Clinical Oncology (ASCO), the American Head and Neck Society (AHNS) and the Society for Immunotherapy of Cancer (SITC).

ABOUT ASTRO
The American Society for Radiation Oncology (ASTRO) is the world's largest radiation oncology society, with more than 10,000 members who are physicians, nurses, biologists, physicists, radiation therapists, dosimetrists and other health care professionals who specialize in treating patients with radiation therapies. The Society is dedicated to improving patient care through professional education and training, support for clinical practice and health policy standards, advancement of science and research, and advocacy. ASTRO publishes three medical journals, International Journal of Radiation Oncology • Biology • Physics, Practical Radiation Oncology and Advances in Radiation Oncology; developed and maintains an extensive patient website, RT Answers; and created the nonprofit foundation Radiation Oncology Institute. To learn more about ASTRO, visit our website and follow us on our blog, Facebook, Twitter and LinkedIn.

ABOUT ASCO
Founded in 1964, the American Society of Clinical Oncology (ASCO) is committed to making a world of difference in cancer care. As the world's leading organization of its kind, ASCO represents more than 40,000 oncology professionals who care for people living with cancer. Through research, education, and promotion of the highest-quality patient care, ASCO works to conquer cancer and create a world where cancer is prevented or cured, and every survivor is healthy. ASCO is supported by its affiliate organization, the Conquer Cancer Foundation. Learn more at www.ASCO.org, explore patient education resources at www.Cancer.Net, and follow us on Facebook, Twitter, LinkedIn, and YouTube.

ABOUT AHNS
The American Head & Neck Society (AHNS) is the single largest organization in North America for the advancement of research and education in head and neck oncology. The mission of the American Head and Neck Society is: to promote and advance the knowledge of prevention, diagnosis, treatment, and rehabilitation of neoplasms and other diseases of the head and neck; to promote and advance research in diseases of the head and neck, and; to promote and advance the highest professional and ethical standards. For more information, visit www.ahns.info.

ABOUT SITC
Established in 1984, the Society for Immunotherapy of Cancer (SITC) is a nonprofit organization of medical professionals dedicated to improving cancer patient outcomes by advancing the development, science and application of cancer immunotherapy and tumor immunology. SITC is comprised of influential basic and translational scientists, practitioners, health care professionals, government leaders and industry professionals around the globe. Through educational initiatives that foster scientific exchange and collaboration among leaders in the field, SITC aims to one day make the word “cure” a reality for cancer patients everywhere. Learn more about SITC, our educational offerings and other resources at sitcancer.org and follow us on Twitter, LinkedIn, Facebook and YouTube.