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 firstname.lastname@example.org for a copy of the abstract or presentation slides from the meeting.
Attribution to the 2020 Multidisciplinary Head and Neck Cancers Symposium requested in all coverage. This release includes updated information not available in the abstract.
More information on radiation therapy and head and neck cancer from RT Answers, ASTRO’s patient education site:
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).
The American Society for Radiation Oncology (ASTRO) is the largest radiation oncology society in the world, with nearly 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. For information on radiation therapy, visit RTAnswers.org. To learn more about ASTRO, visit our website or media center, and follow us on social media.