Could you give us a brief overview of the SCORES trial?
The SCORES trial was a two-part study; the first part, to find the tolerable doses of two immune modulators with different MOAs in combination with an anti-PD-L1 antibody termed durvalumab. We’ve known that durvalumab and its class of drugs has activity in several cancers and the idea behind this study was to investigate whether combination immunotherapy working under different complimentary mechanisms would improve that activity. One of the drugs was an inhibitor of a gene termed STAT3 and the other was an inhibitor of a cytokine CXCR2. Both of those have properties that would suggest they would augment activity of checkpoint inhibitors, so the first part of the study designed to see if they could be combined feasibly, and then the second part of the study was looking at cohorts of head and neck cancer patients to see if there was activity.
Could you tell us about the potential clinical impact of the SCORES trial?
The impact really focused on the combination of the STAT3 inhibitor and durvalumab, especially in patients who had never had checkpoint inhibitor immunotherapy previously. What we demonstrated was a high response rate in those patients – much higher than one would expect to see with durvalumab alone. The clinical impact would be that we can potentially improve on immunotherapy significantly by combining different immunotherapy agents, in this case specifically, an anti-PD-L1 antibody and a STAT3 inhibitor. The results of course are preliminary but the potential impact could be quite broad: not only helping patients with recurrent or metastatic disease, but even in the curative setting, in locally advanced disease and anywhere in between, when we have a combination that appears to work very well and is well tolerated.
Do you think there is a future for combination therapy in head and neck squamous cell carcinoma? What is the scientific rationale for the combination being tested in the SCORES study?
Definitely; I think we’re now seeing multiple data sets that would suggest that when we combine immunotherapy drugs with different mechanisms of action we see potentiation. Most if not all of these studies have worked on a backbone of an anti-PD-1/anti-PD-L1 antibody, because we know those have single agent activity. But we also know that the majority of patients will not respond, unfortunately, and will not benefit. We have the proof of principal that immunotherapy can work, but it’s limited in how many patients it works in.
By combining immunotherapies, we can begin to broaden this scope of patients and the patients who benefit greatly with these drugs, and that’s exactly what this combination does. Where the anti-PD-L1 antibody works primarily on activating T cells, the STAT 3 inhibitor works on negating the immunosuppressive microenvironment within a tumor and we know that that is very important in head and neck cancer. By combining these, what we end up delivering is a combination that is highly effective. Furthermore, when we look closely at the nature of the responses what we see in many of those patients is not only that they are responding but that they are having very deep responses. About half the responses were complete remissions and what we’ve known so far with immunotherapy is that in those patients that have a complete response or near-complete response, those patients appear to benefit for a very long time – not just months, but even years. Obviously, if we can have more patients with those types of responses, that would be better for the field and for patients.
What talks did you most enjoy at the ESMO Congress this year?
I think there were a few great abstracts, if you don’t mind me giving you more than one. I think the PACIFIC data in lung cancer – the adjuvant trial in Stage III lung cancer – was critically important to the field: a demonstration in an epithelial solid tumor (non-melanoma) that adjuvant therapy is beneficial.
I really liked Bonnie Glisson’s presentation of an HPV vaccine in combination with anti-PD-L1 antibody nivolumab, demonstrating that one could generate T-cell responses to HPV and perhaps increase response rate.
In addition to that, there were a couple of other presentations in the head and neck-specific section. I had an opportunity to present KEYNOTE-040, which was a large randomized trial of pembrolizumab versus standard of care in recurrent or metastatic disease that demonstrated efficacy of pembrolizumab in that setting.
My colleague Robert Haddad presented the data on nivolumab continuation after progression in a randomized trial, demonstrating that even after progression, it seems like patients can continue to benefit from immunotherapy. I think we continue to see more and more promise for immunotherapy, different settings where these agents work and combinations of immunotherapy drugs that seem to potentiate each other; and there continues to be a tremendous amount of excitement around immunotherapy in multiple diseases.
How would you like to see treatment options for head and neck cancer advance over the next 5 years?
What I would really like to see is greater efficacy in a recurrent metastatic setting – I think we will achieve that through combination immunotherapy. Then I’d like to see these drugs move into the curative intent setting, where most of our patients with head and neck cancer are; about 90% will present with locally advanced disease. That is an opportunity not only to cure more patients as they present, but also, as immunotherapy gets further and further integrated, maybe make the existing therapies more tolerable – lower the doses of radiation, perhaps do fewer invasive surgeries – with the idea that immunotherapy now can augment those other modalities and continue to preserve or improve our cure rates while treating patients in a less toxic manner. Of course, there’s research in all those directions, and that’s what we’re aiming for in the next few years.
Any closing comments?
I think the SCORES study really illustrates two very important principals. One, that it appears that we can improve response rates in head and neck cancer by combining immunotherapies. It looks like STAT3 inhibition is an important mechanism of tumor immunosuppression and reversing that produces what looks to be very promising efficacy. Two, the field is quickly moving forward with immunotherapy, not only in head and neck cancer but in multiple cancers, and we’re beginning to see them in earlier and earlier settings in the disease, and I think that trend will clearly continue. These are very exciting times.
Ezra Cohen, MD, is a board-certified oncologist and cancer researcher. He cares for patients with all types of head and neck cancers, including esophageal, thyroid and salivary gland cancers.
Cohen is also an internationally recognized expert on novel cancer therapies and heads the Solid Tumor Therapeutics program at Moores Cancer Center (CA, USA). Much of his work has focused on squamous cell carcinomas and cancers of the thyroid, salivary gland, and HPV-related oropharyngeal cancers. As a physician-scientist, he is especially interested in developing novel therapies and understanding mechanisms of sensitivity or resistance; cancer screening; and using medication and other agents to delay or prevent cancer (chemoprevention). He was recently appointed chair of the National Cancer Institute Head and Neck Cancer Steering Committee, which oversees NCI-funded clinical research in this disease.
Cohen is editor-in-chief of Oral Oncology, the most respected specialty journal in head and neck cancer. A frequent speaker at national and international meetings, he has authored more than 120 peer-reviewed papers and has been the principal investigator of multiple clinical trials of new drugs in all phases of development. Cohen completed a hematology/oncology fellowship at the University of Chicago, where he was named chief fellow. He completed residencies in family medicine at the University of Toronto and in internal medicine at Albert Einstein College of Medicine. Cohen earned his medical degree at University of Toronto. He is board certified in internal medicine and medical oncology.
Financial disclosure/ conflict of interest statement
Consulting/advisory role with Eisai, Pfizer, Merck, BMS and Human Longevity. The study was sponsored by AstraZeneca.