Can a simple blood test tell you how your cancer therapy works? 

According to a recent study published in Nature Medicine, blood from patients can be used to screen circulating tumor DNA (ctDNA) and can provide insights about the success of therapy and if any course correction is required.  

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The Cancer Research Institute (CRI) is delighted to share the latest research from CRI-Torrey Coast Foundation GEMINI CLIP Investigators Valsamo Anagnostou, MD, PhD, and Vincent K Lam, MD, from Johns Hopkins University. The article also features two CRI-affiliated co-authors — CRI Lloyd J. Old STAR Kellie N. Smith, PhD, and SU2C-CRI Cancer Immunology Dream Team Investigator and CRI Scientific Advisory Committee member Drew M. Pardoll, MD, PhD. 

The paper reports results from the phase Ib trial that evaluated the safety and efficacy of two immunotherapeutics — nivolumab alone or nivolumab in combination with relatlimab, in a pre-operative setting alongside chemoradiotherapy in patients with resectable stage II or stage III gastroesophageal cancer. The study, involving 32 patients, tested patient response to the therapy using various endpoints including pathological responses and survival rates. 

Both single and combination immunotherapy-treated groups showed significantly higher response rates compared to historical data from chemoradiation-treated patients. Pre-treatment of patients with immunotherapy along with chemo-radiotherapy before surgery improved patient outcomes as measured by different study endpoints — complete pathological response, major pathological response, overall survival, and recurrence-free survival.

Apart from conventional pathological response evaluations, the study also employs a dynamic assessment of ctDNA in the bloodstream of patients at different time points to evaluate the efficacy of therapy. The absence of ctDNA pre-surgery was correlated with higher overall survival and recurrence-free survival in patients. These findings provide valuable insights both into the potential of neoadjuvant immunotherapy in improving outcomes for gastroesophageal cancer patients and the use of liquid biopsies to assess a patient’s response to therapy and potentially predict long-term outcomes.

Dr. Anagnostou has previously employed this novel ctDNA-based approach for metastatic lung cancer patients in a Nature Medicine paper. 

Why is this important?  

There has been minimal progress in the management and treatment of gastroesophageal cancer over the last decade. The results from this newly published trial propose a new therapy regimen using immunotherapy in combination with chemoradiotherapy as a first-line treatment for gastroesophageal cancers.  

The study also highlighted the potential of liquid biopsies. By analyzing patient blood samples for ctDNA, researchers were able to assess the efficacy of therapy with great reliability. In a recent discussion, Dr. Anagnostou emphasized the limitations of relying solely on pathologic response as a measure of clinical outcome. She pointed out that patients who do not respond to therapy can have inherent differences among them, stating, “You can further refine that group based on liquid biopsies.”  

This trial is the first in gastroesophageal cancer patients, to investigate the safety, feasibility, and efficacy of neoadjuvant immune checkpoint inhibitors — especially in combination with chemoradiotherapy — together with testing biomarkers of clinical response. For these patients, expansion and follow-up studies like this one are a crucial next step to helping create a world immune to cancer. 

Want to do something big for cancer immunotherapy research? Donate today to the Cancer Research Institute.