Neoadjuvant immunochemotherapy for nonsurgical HPV-negative head and neck cancer

Abstract

Giving immunotherapy with chemotherapy before radiation to nonsurgical patients with locoregionally advanced human papillomavirus (HPV)–negative head and neck cancer may improve treatment efficacy according to the phase 2, nonrandomized De-Escalation Therapy for Human Papillomavirus Negative Disease trial published in JAMA Oncology.¹

In this trial of 36 nonsurgical patients with stage IVa/b HPV-negative head and neck squamous cell carcinoma, 53% of the patients had a deep response (i.e., >50% tumor shrinkage per the Response Evaluation Criteria in Solid Tumors) after receiving neoadjuvant nivolumab plus chemotherapy (carboplatin and paclitaxel) before radiation. The deep response rate after neoadjuvant nivolumab plus chemotherapy met the primary endpoint of an improvement over the historical control of induction chemotherapy alone. Of the full cohort, 86% achieved an objective response (≥30% tumor shrinkage).

Investigators also tested the ability to de-escalate the radiation dose and volume among the deep responders after neoadjuvant immunochemotherapy. Compared to the 16 patients who were assigned to standard chemoradiation, the 19 patients who received de-escalated chemoradiation had fewer acute toxic effects during treatment and fewer distant metastases.

“Taken together, this suggests that neoadjuvant immunochemotherapy may improve outcomes in locoregionally advanced HPV-negative head and neck cancer, while also selecting patients who can do well with lower doses and volumes of radiation, which can lead to fewer side effects,” says the lead author of the study, Ari Rosenberg, MD, an oncologist and assistant professor of medicine at the University of Chicago Medicine who specializes in immunotherapy and other treatments for head and neck and thyroid cancers.

Programmed death ligand 1 (PD-L1) was a predictive biomarker for a response to chemoimmunotherapy and survival. Progression-free survival at 24 months was 88% for patients with PD-L1 expression with a combined positive score (CPS) of 20 or more but 59% for patients with PD-L1 expression with a CPS of less than 20 (p = .16). The overall survival rates were 88% and 69%, respectively.

He says that the study builds on data from the KEYNOTE-689 study, which showed improved event-free survival with neoadjuvant immunotherapy for patients with surgically treated head and neck cancer. The phase 3 study found that the addition of neoadjuvant pembrolizumab to the standard of care (surgery and adjuvant radiotherapy with or without concomitant cisplatin) resulted in improved event-free survival at 36 months in comparison with the standard of care alone (57.6% vs. 46.4%; p = .008). The study also found a significant improvement in event-free survival for patients whose tumors expressed PD-L1 with a CPS of 10 versus those treated with the standard of care alone (59.8% vs. 45.9%; p = .004).²

“Our data supports this [use of neoadjuvant immunochemotherapy] for the non-surgical population,” says Dr Rosenberg.

Dr Rosenberg and his colleagues are planning a follow-up study that will open to accrual soon to build on these phase 2 data. He emphasizes that studies building on the KEYNOTE-689 trial are warranted to test neoadjuvant immunochemotherapy in nonsurgically treated patients with chemoradiation. He also says that further trials are needed on treatment de-escalation for patients with HPV-negative head and neck cancer.