ASCO 2016 Update: Immunotherapy’s Impact in Head & Neck Cancers

New breakthroughs presented at ASCO16 should give patients with head and neck cancers hope that that better treatment options are on the horizon as immunotherapies may soon be more widely available. The need for new treatments is urgent: current standard-of-care chemotherapies have produced limited benefit in patients with advanced head and neck cancers, according to Robert L. Ferris, MD, PhD, FACS, of the University of Pittsburgh Medical Center. Additionally, as noted by Andrew Sikora, MD, PhD―who participated in our expert panel discussion about the latest news from ASCO for patients ―our efforts to treat these patients more effectively are hampered by a lack of robust predictive and prognostic biomarkers.

Results from a phase 3 trial presented by Ferris highlighted the effectiveness of nivolumab immunotherapy, an anti-PD-1 checkpoint antibody, in patients with advanced head and neck cancer. Rates of response and survival in patients who received nivolumab were double those of chemotherapy-treated patients. Also, patients with higher PD-L1 expression, whose activity is blocked by nivolumab, achieved superior outcomes. Furthermore, nivolumab was also safer, as only 13.6% of immunotherapy-treated patients experienced Grade 3 or 4 treatment-related adverse events, compared to 35.1% of chemotherapy-treated patients.

Next, the first phase 2 trial to show the effectiveness of pembrolizumab, an anti-PD-1 checkpoint antibody, in chemotherapy-refractory head and neck cancer patients was presented by Josh Bauml, MD, of the University of Pennsylvania. Compared to a 5-6% response rate after chemotherapy, 17% of patients responded while another 19% saw their disease stabilize after pembrolizumab treatment. These responses also lasted, with 75% of them still ongoing after 6 months.

Data from a phase 1 pembrolizumab trial presented by Ranee Mehra, MD, of the Fox Chase Cancer Center, showed similar response rates (~18%) compared to the aforementioned phase 2 trial. Complete responses were achieved, and many responses appeared durable: 85% lasted for at least 6 months, 71% for at least 1 year, and 65% overall. When analyzing pembrolizumab-treated patients according to their HPV-status, Mehra found that responses were higher in the HPV+ patients (24% vs 16%), but she and others cautioned that it is still too early to definitively determine the role of HPV in pembrolizumab responses.

Laura Chow, MD, of the Seattle Cancer Care Alliance, also performed in-depth analysis of immune biomarkers in that phase 1 trial, to identify the patients most likely to respond to immunotherapy. She found that higher expression of PD-L1 and PD-L2 were both associated with improved responsiveness and survival. Importantly, this trend only applies when looking at both tumor and immune cells. It was particularly pronounced for PD-L2 expression, with 23% of PD-L2+ patients responding compared to only 10% of those without. Higher IFN-g signaling, which controls many aspects of the adaptive immune response, was also significantly associated with improved outcomes.

Sikora, who spoke at two separate sessions relating to immunotherapy in head and neck cancer, ended by emphasizing the necessity of using biomarkers like PD-L1/PD-L2 and IFN-g expression to improve our ability to treat patients with head and neck cancer. They offer the ability to do this not only by suggesting ways that immunotherapy could complement surgical and targeted approaches, but also by using them to determine the optimal immunotherapy combos needed to address the specific immune characteristics of individual tumors.