Immunotherapeutic Strategies in Head and Neck Cancer

Both HPV-positive and -negative head and neck cancers are "outstanding candidates for immunotherapeutic strategies," said Andrew G. Sikora, MD, PhD, Baylor College of Medicine, at the 2014 Chemotherapy Foundation Symposium.

Andrew G. Sikora, MD, PhD

Both HPV-positive and -negative head and neck cancers are “outstanding candidates for immunotherapeutic strategies,” said Andrew G. Sikora, MD, PhD, Baylor College of Medicine, at the 2014 Chemotherapy Foundation Symposium. This should mean a positive outlook for the future management of these diseases, Sikora said, because “Immunotherapy is the only self-evolving and self-amplifying therapy we have that can keep up with cancer cells.”

The current standard of care for advanced HPV-positive head and neck cancer (mostly stage III/IV at presentation) is chemoradiotherapy (CRT) or transoral surgical resection with adjuvant CRT. Data have shown overall survival rates higher than 80% in HPV-positive patients. Sikora said that, “Since both short- and long-term morbidities of combination therapy can be considerable, immunotherapy is an attractive strategy for therapeutic de-escalation while maintaining activity against systemic and minimal residual disease.” He noted, that since standard treatment options have highly positive outcomes in this setting, physicians should carefully integrate immunotherapeutic approaches.

Describing the immunotherapeutic outlook in HPV-positive patients, Sikora said, “the presence of well defined foreign viral antigens provides a unique opportunity for antigen-specific immunotherapy, including vaccines and adoptive cell-transfer approaches targeting HPV oncoproteins.”

For patients with advanced HPV-negative disease, standard treatment options include surgery followed by CRT or primary CRT with surgical salvage. Regarding immunotherapy in these patients

Sikora said, “While the broad mutational landscape of carcinogen-induced tumors has proven a barrier to identification of consistently expressed tumor antigens targetable by antigen-specific vaccination and adoptive therapy approaches, this also creates the potential for expression of large numbers of potentially immunogenic mutated neoantigens.”

Sikora also noted that while both HPV-positive and -negative head and neck cancer have unique antigenic profiles, both cancers have highly suppressive immune microenvironments. “The good news is that head and neck cancers are highly immunogenic cancers; however, the bad news is that head and neck cancer is also profoundly immunosuppressive.” Thus, Sikora said, there seems to be a convincing rationale for using PD-1, PD-L1, and CTLA-4 checkpoint inhibitors in both disease subtypes.

A final consideration Sikora mentioned was how the immunotherapeutic landscape in head and neck cancer changes once patients receive standard of care therapy. “The immune landscape of head and neck cancer is complicated and then it gets more complicated when we bring in what treatment does to our patients.”

Phase II ADX11-001 Trial

Regarding ongoing immunotherapy research in head and neck cancer, Sikora discussed his industry-sponsored window of opportunity phase II trial of the listeria-based HPV vaccine ADX11-001 (NCT02002182).

The study is accruing newly diagnosed patients with stage II-IV HPV16-positive oropharynx squamous cell carcinoma (OPSCC) who are scheduled to receive ablative transoral robotic surgery (TORS). The hypothesis for the trial is that ADX11-001 will induce circulating and tumor-infiltrating antigen-specific T cells in these patients.

The primary endpoint of the trial is change in HPV E6/E7-specific CD8-positive cytotoxic lymphocyte responses and the secondary endpoint is toxicity.

The accrual goal for the trial is 30 patients and Sikora said “We’ve accrued a quarter of the patients in this phase II window of opportunity trial focusing on immunologic and biologic correlates that are going to give us a really good idea of how this approach works.”

Sikora added, “This is the type of trial that head a neck cancer is really good for—a window of opportunity study where our ability to access the tumor becomes a real advantage."


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