Daniel Zandberg, MD
PD-1/PD-L1 inhibitors continue to play an important part in the treatment paradigm for patients with head and neck cancer, as ongoing clinical trials are exploring additional agents.
, Dan Zandberg, MD, an assistant professor at the University of Maryland School of Medicine, discussed results from the HAWK study as well as current combination approaches for patients with head and neck cancer.
OncLive: Can you please summarize the results of the HAWK trial?
The HAWK trial is a phase II trial in recurrent metastatic head and neck cancer for patients who had PD-L1–high expression, defined as greater than 25% tumor cell expression. Promising outcomes were observed. The ORR was 16% with durable responses seen, with 55% ongoing at data cutpoint. The median OS was 7 months with a 1-year survival of 33%.
Additionally, patients with HPV-positive versus HPV-negative disease were evaluated in an exploratory fashion with HPV-positive patients having a response rate higher at 30% compared with 10%, and longer survival. Overall, the results are promising in a single-arm phase II trial, with ongoing phase III trials with durvalumab.
What are your thoughts on identifying biomarkers for immunotherapy?
Biomarkers are very important for immunotherapy. Currently in head and neck cancer, there is not a biomarker that is required for treatment with nivolumab (Opdivo) as part of the standard of care; however multiple biomarkers continue to be explored in addition to PD-L1 expression.
Currently, the promise of immunotherapy is not that everybody responds to single agent anti–PD-1/PD-L1 therapy, but rather for those who do respond, a large portion of them achieve a significant duration of response. That speaks to the importance, especially as new combinations are tested, of continuing to identify better biomarkers beyond PD-L1 expression, to better predict what patients will derive the most benefit from these agents.
What combination approaches with other checkpoint inhibitors are being investigated?
Currently anti-PD-1 and anti-PD-L1 monoclonal antibodies are being combined with targeted agents and other immunotherapy agents, including durvalumab, to enhance the number of patients that benefit from immunotherapy.
At the 2017 ASCO Annual Meeting, combination anti-PD-1 mAb with IDO1 inhibitor showed promising results. As presented at ESMO, Durvalumab was combined with a STAT3 inhibitor and has also shown early promise.
What are some other effective strategies?
It is important for us to be able to better understand and manipulate the immunosuppressive tumor microenvironment. For example by trying to block cosignaling molecules beyond PD-1/PD-L1, such as TIM-3 and LAG3.
What also may be important is targeting other pathways that may affect the immune system’s ability to attack the tumor, such as interferon gamma signaling pathways where JAK mutations have been observed to confer resistance.
Can you discuss the potential of these agents in the neoadjuvant setting?
As typically seen in oncology, agents get tested in most refractory settings first and then move to be tested in earlier stages. It's exciting in head and neck cancer with having anti–PD-L1/PD-1 therapy—being combined with radiation in the locally advanced setting—based on the potential pro-immunogenic properties of radiation.
Already ongoing are randomized phase III trials looking at chemoradiation plus immunotherapy versus chemoradiation alone. It's an exciting time; it has potential to change the standard of care in the upfront setting, which is important. The HPV-positive patients do very well in the locally advanced setting. However, we still have a great need for improvement of outcomes in the HPV negative oropharyngeal cancer patients as well as the other sites in the head and neck.
Zandberg D, Algazi A, Good JS, et al. Durvalumab for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): preliminary results from a single-arm, phase 2 study. In: Proceedings from the 2017 ESMO Congress; September 8-12, 2017; Madrid, Spain. Abstract 1042O.
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