Robert Ferris, MD, PhD

In this issue we recognize an important cause of cancer in men and women: the human papillomavirus (HPV). Nearly 20% of the world’s cancer cases are caused by viruses, and 7 viruses have been documented to cause this aggregate number of cancer cases, with HPV being the most well recognized. This notoriety stems from its etiologic activity as a major cause of cervical cancer, anal cancer, and, in a rapidly increasing set of cases with a 3:1 male-to-female ratio, head and neck squamous cell carcinoma (HNSCC).

Since 2018, March 4 has been designated as International HPV Awareness Day. The goal is to promote awareness of HPV as a major cause of these cancers because it is preventable through vaccines that are highly efficacious. The success of the HPV vaccine is reminiscent of the recent advancements leading to efficacious vaccines that prevent or ameliorate coronavirus disease 2019 (COVID-19). The worldwide impact of the HPV vaccine is just as potent.

The special report in this issue, “HPV-Targeted Vaccines Combined with PD1 Inhibition Promise to Transform The Treatment of HPV-positive Head and Neck Cancers” (pages 28-31) describes strategies for therapeutic HPV vaccination in conjunction with standard chemo-radiation approaches or more favorably combined with anti–PD-1 immunotherapies. Therapeutic HPV vaccination must be targeted against the oncogenes expressed during cancer progression (oncogenes E6 and E7), whereas the prevention vaccine can target surface capsid of the virion, much like the COVID-19 vaccine targets the spike protein to prevent cellular entry.

We are pleased to review the exciting advances in therapeutic cancer vaccines as antiviral strategies, recognizing the wonderful accomplishments in HPV cancer prevention. We need to continuously test therapeutic HPV strategies in HSNCC, which has overtaken cervical cancer as the most common HPV-associated cancer, in North America. The future is bright, and translational science is working.

Articles

Nearly 20% of the world’s cancer cases are caused by viruses, and 7 viruses have been documented to cause this aggregate number of cancer cases, with HPV being the most well recognized. 

Translational Medicine Forges Ahead in HPV-Associated Cancers

Looking back on the long and difficult year that was 2020, 1 of the positive events was the Society for Immunotherapy of Cancer (SITC) Annual Meeting held virtually in November. 

The meeting was led by outgoing SITC president Mario Sznol, MD, professor of medical oncology and coleader of the cancer immunology program at Yale University in New Haven, Connecticut. Given the success of cancer immunotherapy, over the years the SITC meeting has become more clinical and translational, as well as biomarker-oriented, involving clinical trials across a variety of cancers. The meeting included public presentation of early phase data manifesting productive collaborations between industry and academic investigators. 

One example comes from an attempt to improve on anti–PD-1 nivolumab (Opdivo) therapy by targeting the tumor microenvironment with eganelisib (IPI-549), which was presented by Ezra Cohen, MD, professor of medicine and associate director of translational service at the University of California, San Diego. Cohen presented updated clinical data from an expansion cohort that included non–small cell lung cancer, melanoma, and squamous cell carcinoma of the head and neck (SCCHN), from the MARIO 1 study (NCT02637531). In the SCCHN expansion cohort, a selective PI3 kinase-γ inhibitor was used to enhance the modest (15% objective response rate) activity of anti–PD-1 nivolumab or pembrolizumab (Keytruda) in SCCHN.

In the expansion cohort (n=21), an overall response rate of 10% was observed, particularly in patients who would not be expected to respond to anti–PD-1 monotherapy, having progressed on their immediate prior therapy with a checkpoint inhibitor. In these patients, a disease control rate of 45% was encouraging, even in a small cohort such as this. More importantly, it proves the concept that targeting macrophages with a PI3 kinase-γ inhibitor may be beneficial. Other therapies targeting PI3 kinase-γ,δ dual inhibitors are ongoing and complement strategies to target the tumor microenvironment and STAT-3 dependent genes.

 Other data presented combined inhibitory strategies with vaccination in pancreatic cancer developed in the laboratory of Elizabeth M. Jaffee, MD, professor of oncology and deputy director of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine in Baltimore, Maryland. In this approach, the GVAX allogeneic tumor cell vaccine strategy was combined with nivolumab and urelumab, which triggers the CD137 pathway. 

In this trial, the previous observation of liver toxicity using CD137 agonism was not observed, suggesting a safe neoadjuvant dosing. Indeed, 30% of patients demonstrated pathologic responses. Further research may combine a way of overcoming immune checkpoint pathways with stimulatory agonists. 

In all, 2020 came to an end with continued progress, and hopes for future meetings in person to enhance direct scientific interchange.

Unique Immunotherapy Combinations Come to the Forefront at SITC Meeting 

Robert Ferris, MD, PhD, vice chair for Clinical Operations, associate director for Translational Research, and coleader of the Cancer Immunology Program at the University of Pittsburgh Cancer Institute, discusses the potential impact the CheckMate-141 study could have regarding nivolumab as potential treatment for patients with head and neck cancer.

Ferris says in the phase III trial, patients with cisplatin-refractory head and neck cancer were randomized to either a nivolumab arm or standard chemotherapy arm. Due to a positive endpoint of overall survival in the nivolumab arm, the study was stopped early and its data added immunotherapy as a fourth modality to the treatment landscape of head and neck cancer, Ferris says.

Videos

Robert Ferris, MD, PhD, discusses the potential impact the CheckMate-141 study could have regarding nivolumab as potential treatment for patients with head and neck cancer.

Robert Ferris, MD, PhD | Authors

Articles

Translational Medicine Forges Ahead in HPV-Associated Cancers

Unique Immunotherapy Combinations Come to the Forefront at SITC Meeting

Dr. Robert Ferris on Additional Data for a Phase III Study Regarding Nivolumab in Head and Neck Cancer