Opdivo in Head and Neck Cancer Represents New Hope and the Culmination of a Career

Robert Ferris has been trying for years to harness the immune system to fight cancer.

“Since I got my MD/PhD 25 years ago in immunology/ immunotherapy, I have dreamed about the potential for reversing the immunosuppression of cancer and stimulating the immune system as a fourth therapeutic modality,” says Ferris, professor and chief, Division of Head and Neck Surgery, vice chair for Clinical Operations, associate director for Translational Research, and coleader of the Cancer Immunology Program at the University of Pittsburgh Cancer Institute.

Recently, Ferris made a significant stride toward achieving that objective.

Along with Maura Gillison, of Ohio State University, Ferris served as the international cochair/coprimary investigator for the phase 3 CheckMate-141 trial. The trial, which examined the anti—PD-1 agent Opdivo (nivolumab) versus investigator’s choice of Erbitux (cetuximab), methotrexate, or docetaxel in patients with platinum-refractory squamous cell carcinoma of the head and neck (SCCHN), was stopped early after it was determined Opdivo had met its primary endpoint of overall survival improvement. Eligible patients will now be able to continue treatment or cross over to receive Opdivo.

"This is what I've devoted my career to, and it is gratifying to see that really come to pass," says Ferris. “To have an anti—PD-1 agent be proven to improve survival in head and neck cancer in a randomized phase 3 trial, and the potential for a new FDA approval in the near future is a game changer. There is now hope for a lot of patients and physicians who have been frustrated by this difficult-to-treat disease. This opens up a whole new class of therapies for this population.”

The phase 3 data have not yet been released. However, early discontinuation of the trial, which was scheduled to run until October 2016, has generated significant excitement in the field, says Ferris, who is a primary author on the abstract submitted for presentation at the annual meeting of the American Society of Clinical Oncology (ASCO).

What prompted the investigation of Opdivo as a treatment for this patient population?

In an interview with CURE, Ferris discusses CheckMate-141, the biggest remaining challenges in head and neck cancer, and the potential for Opdivo as a treatment of patients with the disease.It is clear that this is a population with a devastating disease that has not had an FDA-approved drug in 10 years. It was 2006 when Erbitux was approved and that was a relatively modest advance, although it was the first targeted therapy. We have a population without any other therapeutic options and a very rapid progression.

What is the current standard of care for patients with SCCHN?

Anti—PD-1 agents have had promising data in melanoma and squamous non–small cell lung cancer (NSCLC). Squamous NSCLC genomically resembles HPV-negative head and neck cancer in its behavior regarding carcinogen exposure. Therefore, we felt it might respond well to anti–PD-1 agents, too. We designed the study to hopefully create something new and effective for an essentially hopeless palliative group of patients. Head and neck cancer, particularly HPV-negative disease, which makes up the majority of recurrence head and neck cancers, is very immunosuppressive. It weakens the immune system and allows the cancer to grow. We thought, “If we could try and reverse that effect, using an anti—PD-1 strategy, that would be fantastic.”It is important to recognize that the standard of care differs throughout the world. We designed this trial to reflect that and included an investigator’s choice agent — Erbitux, methotrexate, or docetaxel. Patients were randomized to either the Opdivo arm or the control arm, and investigators were able to select the agent that those in the control arm received.

We still don’t have public data for what all of the standard of care selections were, but we do know that Erbitux tends to be used more in North America. Meanwhile, the other two agents are more likely to be used in Europe and other countries because Erbitux is not approved there.

What do you think the reaction will be once the data from this trial are released?

The benefits are really very modest with those single-agent treatments and they are toxic. There is very much a need for a new treatment. We are very interested in the toxicity profile of Opdivo, as it has proven to be well tolerated in other cancers.We do have single-agent data from the 2015 ASCO Annual Meeting with a very similar agent, Keytruda (pembrolizumab) in head and neck cancer. The data for anti—PD-1 with either Keytruda or Opdivo appear to be very similar, in different cancer types in terms of the efficacy and side effect profile.

Therefore, there was a suspicion that Opdivo would be promising in head and neck cancer, as well. There is a great deal of buzz from medical oncology leaders all over the country regarding this. People have really been waiting with bated breath for something for our patients. This is a real win for the community and for a population of patients with a devastating disease in a very important area of the body.

Do you see the use of Opdivo expanding into other settings in head and neck cancer?

This disease can disrupt speaking, drinking, swallowing, and has catastrophic consequences. I expect enthusiasm and support from the community regarding this.This data reinforces the fact that many ongoing clinical trials are looking at anti—PD-1 agents in head and neck cancer. We are on the way to moving it earlier in the disease. I see it being used not only in first-line recurrent disease, but also in locally advanced disease.

I am running a trial through the Radiation Therapy Oncology Group in previously untreated patients with curable head and neck cancers with Opdivo. There are trials in first-line, combination trials with Opdivo planned in all settings, and one is opening in the near future for curative, locally advanced, high-risk patients with head and neck cancer.

For these patients, survival has not really improved in the last few decades, so we are going to intensify their treatment by adding Opdivo to standard therapy. I think the future will include adding Opdivo to current therapy and, in some cases, replacing chemotherapy. There is a lot of potential for this agent.