Barbara Burtness, MD

Barbara Burtness, MD, professor of Medicine, Medical Oncology, Disease Aligned Research Team Leader, Head and Neck Cancers Program, co-director of the Developmental Therapeutics Research Program, Yale Cancer Center, discusses the effectiveness of immunotherapy in patients with platinum-refractory head and neck cancers.

The first step in establishing that immunotherapy is active in head and neck cancers was to show that there are targets for the immune system, says Burtness. Evidence suggests that the targets in head and neck cancer can be infiltrated by neoantigenic tumor-associated immune cells with the mutational load seen in human papillomavirus (HPV)—negative and -positive cancers. Data from early trials suggest that the higher the mutational load, the more likely patients will experience a partial or complete response, according to Burtness.

The phase Ib KEYNOTE-012 trial was the first to examine the use of the PD-1 inhibitor pembrolizumab (Keytruda) in patients with head and neck cancer. Results showed that the agent was active in patients with platinum-refractory disease, regardless of HPV status, says Burtness. The phase II KEYNOTE-055 trial followed; results showed that pembrolizumab was also active in patients with cetuximab-refractory disease, according to Burtness.

The phase III CheckMate-141 trial compared the use of the PD-1 inhibitor nivolumab (Opdivo) versus investigator’s choice of standard-of-care chemotherapy in patients with platinum-refractory disease. Results showed the median overall survival was 7.5 months in the nivolumab arm versus 5.1 months in the chemotherapy arm.

These trials present positive evidence supporting the use of PD-1 agents in head and neck cancer, according to Burtness, with modest response rates ranging from 16% to 20%. These data led to FDA approvals in platinum-refractory head and neck cancer, concludes Burtness.

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Barbara Burtness, MD, discusses the effectiveness of immunotherapy in patients with platinum-refractory head and neck cancers. 

Dr. Burtness on the Effectiveness of Immunotherapy in Head and Neck Cancers

Barbara Burtness, MD, professor of Medicine, Medical Oncology, Disease Aligned Research Team Leader, Head and Neck Cancers Program, co-director, Developmental Therapeutics Research Program, Yale Cancer Center, discusses the future of immunotherapy in head and neck cancer.

The logical next step in bringing immunotherapy to the clinic would be to evaluate validated immunotherapy combinations. However, these approaches have not panned out in patients with head and neck cancer, says Burtness. There is a lot of interest in exploring inducible T-cell costimulatory targets and co-inhibitory targets such as OX40. In human papillomavirus-associated cancer, combinations of vaccines and PD-1 inhibitors have shown strong signals of activity.

There is also a lot of interest in exploring the combination of immunotherapy and targeted therapy. There have not been an abundance of data to emerge in this setting, but there are trials evaluating immunotherapeutic agents with cetuximab (Erbitux). Antiangiogenic agents such as ramucirumab (Cyramza), bevacizumab (Avastin), and lenvatinib (Lenvima) also appear to be promising targeted therapies worth exploring in combination with immunotherapy, says Burtness. Moving forward, Burtness is hopeful that the field will place greater emphasis on personalized and sequential treatment strategies.

Barbara Burtness, MD, professor of Medicine (Medical Oncology); Disease Aligned Research Team Leader, Head and Neck Cancers Program; co-director, Developmental Therapeutics Research Program; of Yale Cancer Center, discusses the future of immunotherapy in head and neck cancer.

Dr. Burtness on the Future of Immunotherapy in Head and Neck Cancer

Barbara Burtness, MD, professor of Medicine (Medical Oncology); Disease Aligned Research Team Leader, Head and Neck Cancers Program; co-director, Developmental Therapeutics Research Program; of Yale Cancer Center, discusses the use of biomarkers in metastatic head and neck squamous cell carcinoma (HNSCC).

A PD-L1 combined positive score (CPS) ≥20 is likely to become a biomarker that will drive treatment decisions for patients with metastatic HNSCC in the near future, says Burtness. With the promise of immunotherapy in this setting, many institutions are now doing PD-L1 testing, says Burtness. PD-L1 expression can either be reported in terms of the proportion of tumor cells stained for PD-L1 or the proportion of stromal cells that stain for PD-L1. Looking at the proportion of positive cells on either tumor cells or immune cells is a novel way for the pathologist to test for the biomarker, says Burtness.

Though, assessing CPS ≥20 is going to require a different reporting algorithm, Burtness notes. If it is going to go forward as a companion biomarker with PD-L1, that will add some complexity to the landscape. Currently, looking at PD-L1 seems to be the standard of care as response rates with pembrolizumab (Keytruda) and nivolumab (Opdivo) are low in the unselected population.

Barbara Burtness, MD, professor of Medicine (Medical Oncology) Disease Aligned Research Team Leader, Head and Neck Cancers Program co-director, Developmental Therapeutics Research Program of Yale Cancer Center, discusses the use of biomarkers in metastatic head and neck squamous cell carcinoma.

Dr. Burtness on the Use of Biomarkers in Metastatic HNSCC

Barbara Burtness, MD, professor of Medicine (Medical Oncology); Disease Aligned Research Team Leader, Head and Neck Cancers Program; co-director, Developmental Therapeutics Research Program; of Yale Cancer Center, discusses the promise of frontline pembrolizumab (Keytruda) in the treatment of patients with metastatic head and neck squamous cell carcinoma (HNSCC).

Although the EXTREME regimen had previously been the best treatment option available in this setting, Burtness says no one actually liked using it due to its toxicity. Patients who receive it are at risk of neutropenia or they can develop rash, and there can be days where they just simply feel ill. The regimen has a response rate of approximately 36% and a median overall survival of about 10.7 months, Burtness says, which are not data that patients are particularly encouraged by. As such, the PD-1 inhibitor can really fill an unmet need.

Moreover, the field is anticipating forthcoming studies combining PD-1 inhibition with chemoradiation in early-stage disease, with the goal of preventing patients from reaching the recurrent metastatic setting. For now, however, it is important to see single-agent pembrolizumab have improved efficacy with no additional toxicity than what is observed with EXTREME. Burtness concludes that the next steps for research will be to generate even more durable responses.

Barbara Burtness, MD, professor of Medicine (Medical Oncology); Disease Aligned Research Team Leader, Head and Neck Cancers Program; co-director, Developmental Therapeutics Research Program; of Yale Cancer Center, discusses the promise of frontline pembrolizumab in the treatment of patients with metastatic head and neck squamous cell carcinoma.

Author | Barbara Burtness, MD

Articles

Dr. Burtness on the Effectiveness of Immunotherapy in Head and Neck Cancers

Dr. Burtness on the Future of Immunotherapy in Head and Neck Cancer

Dr. Burtness on the Use of Biomarkers in Metastatic HNSCC

Dr. Burtness on Promise of Frontline Pembrolizumab in Metastatic HNSCC