A study recently published in Nature Medicine sheds light on the potential role of liquid biopsies in the management of advanced non-small cell lung cancer patients undergoing immunotherapy.

The Canadian Cancer Trials Group (CCTG), a division of the Cancer Research Institute at Queen’s University, completed the first phase of the BR.36 clinical trial with partners and researchers across Canada and the United States to demonstrate how circulating tumor DNA (ctDNA) analysis can become a pivotal tool for assessing early responses to immunotherapy and guiding treatment plans.

Janet Dancey, CCTG’s Director, is optimistic about the potential of ctDNA monitoring in steering treatment recommendations, enabling early identification of treatment failure at a time where patients remain well enough to consider alternative options. The results underscore the profound impact this research is poised to make in the field of personalized cancer therapy.

Using liquid biopsy and assessing ctDNA is a new and innovative approach designed to overcome current limitations by providing a dynamic assessment of treatment effect and changes in mutations in the cancer. ctDNA is the genetic material shed by tumor cells into the bloodstream, and enables real-time insights into treatment effect on cancer and also the presence of specific mutations.

“Serial assessment of ctDNA may displace imaging in providing early and accurate assessment of treatment benefit or failure for patients with lung cancer,” Dr. Dancey says. “This approach is ongoing and provides information to better align patients with a therapy option that is best suited for them.”

Implications for lung cancer treatment

The landscape of cancer treatment is rapidly evolving, with researchers studying innovative ways to assess how a treatment is working in patients. Traditional methods like imaging that assess treatment effects and biomarkers, such as PD-L1 expression and tumor mutation burden (TMB) used to assess likelihood of benefit from immunotherapy, often fall short in accurately predicting treatment outcomes.

The BR.36 trial has two phases: the first phase of the trial showed that ctDNA response, defined as the disappearance of ctDNA, with an 82 per cent success rate, can reliably indicate how well treatment is working when compared to traditional radiographic methods. Patients who showed a ctDNA response through the clearance of ctDNA experienced a significantly longer period without cancer progression, with a median of 5.03 months, in contrast to those without such a response, who had only a median of 2.6 months of progression-free survival.

This breakthrough not only highlights ctDNA’s ability to assess treatment effectiveness but also across other cancers. It opens new avenues for more effective patient care through quick, minimally invasive molecular analyses to guide treatment decisions.

“ctDNA is detectable not only in patients with advanced lung cancer but also in other cancer types that may be treated with immunotherapy,” Dr. Dancey says. “It may serve as an indicator of a patient’s response to various cancer treatments, not limited to immunotherapy alone. ctDNA is also detectable in some patients with early-stage cancer, potentially providing insights into the risk of relapse, which can aid in tailoring pre and post-surgical management with drug treatments.”

Next steps in personalized cancer therapy

These initial results show the potential of ctDNA response as a crucial tool in tailoring lung cancer treatment and have laid the foundation for clear next steps. As the trial continues, ctDNA will be leveraged to identify patients at high risk of disease progression. These patients will be randomized into either receiving intensified treatment with pembrolizumab and chemotherapy or continuing with pembrolizumab alone.

The Cancer Research Institute (CRI), and the Canadian Cancer Society (CCS) are supporting the trial which could lead to the approval of ctDNA detection assays as a standard means of assessing the effectiveness of cancer immunotherapies.

For more information on this research, read the full article published in the journal Nature Medicine.

About the Canadian Cancer Trials Group 

The Canadian Cancer Trials Group (CCTG) is a national collaborative research group who design and conduct clinical trials in cancer therapy, supportive care, and prevention across Canada. It brings together a national group of researchers, physicians, scientists, statisticians, and patients, and are internationally recognized for their efforts in discovering treatments that improve outcomes for individuals with cancer.

The CCTG operations and statistics centre is located at the Cancer Research Institute at Queen's University, home to in-house faculty researchers, including clinician scientists, community health and epidemiology researchers, and biostatisticians. The CCTG is a national program of the Canadian Cancer Society (CCS), the only non-American partner of the US National Clinical Trials Network, and collaborates with research cooperative groups worldwide. These global partnerships are pivotal to the success of their cancer clinical trials and play a crucial role in advancing the cancer research agenda in Canada.