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Understanding the SINERGY Trial: A More Personalized Approach to Treating Head & Neck Cancer

Each year, roughly 73,000 people are diagnosed with head and neck cancer, and approximately 90% of head and neck cancers are squamous cell carcinomas (HNSCC) (JAMA). For survivors whose cancer has returned or spread (known as recurrent or metastatic head and neck squamous cell carcinoma), deciding on the right treatment plan can be especially challenging. The current standard of care is based on a large study called KEYNOTE-048, where patients typically receive immunotherapy alone, or immunotherapy combined with chemotherapy as first-line treatment.

What the SINERGY Trial Studied

The SINERGY trial looked at whether doctors could use Signatera™, a personalized tissue-informed blood test that looks for tiny fragments of ctDNA (circulating tumor DNA), to guide treatment decisions in real time. The study included 27 people with recurrent/metastatic head and neck squamous cell carcinoma who may have received chemotherapy and/or radiation previously, but had not received immunotherapy.

By measuring changes in ctDNA levels over time, providers can get an early signal indicating whether treatment is working. Based on certain markers in their tumor (PD-L1), some patients were started on immunotherapy alone, while others were started on immunotherapy with chemotherapy.

If ctDNA levels decreased, this suggested patients could continue on immunotherapy alone or, if originally receiving immunotherapy with chemotherapy, their treatment could be de-escalated and chemotherapy could be stopped. If ctDNA levels increased, this suggested they might benefit from treatment intensification with the addition of chemotherapy.

What the study found

Chemotherapy can be life-saving, but it can come with a host of lifelong side effects and sometimes serious complications. For patients with recurrent or metastatic head and neck cancer, this study offers hope for more precise and potentially less toxic treatment options.

For Signatera-Negative Patients

  • 74% of patients (20 out of 27) were de-escalated from chemo-immunotherapy to immunotherapy alone, resulting in an average of 2 chemotherapy cycles, compared to the standard 6 cycles.
  • Patients also experienced fewer serious side effects compared with what is typically seen with the current standard of treatment.

For Signatera-Positive Patients

  • Positive ctDNA results were used to intensify treatment with chemotherapy, adding it when needed and removing it when possible based on ctDNA returning to undetected.

What Signatera Is and How It Works

Signatera is a personalized blood test designed to detect very small amounts of circulating tumor DNA (ctDNA) in the bloodstream. These small fragments of DNA can sometimes remain in the body after treatment or appear if cancer begins to return.

Signatera is used across many types of cancers to help doctors better understand what may be happening in a patient’s body over time, including whether cancer may still be present or how it may be responding to treatment.

The test is personalized for each patient:

  1. A sample of your tumor tissue is analyzed to identify the unique DNA changes in your cancer.
  2. A custom Signatera test is designed specifically for you.
  3. Your blood is checked regularly to see whether circulating tumor DNA is present and how it changes over time.

This information may help your care team make more informed decisions about your care.

If you or a loved one have head and neck cancer, talk to your care team about whether ctDNA monitoring may be appropriate for your care. To learn more about Signatera testing, please visit: Signatera™ Patients.