International Study Shows Liquid Biopsies May Improve Lung Cancer Survival

Joyce Tyson

After a liquid biopsy revealed that her cancer had a mutation in a gene called RET, Joyce Tyson was able to receive a targeted therapy to treat her lung cancer.

  • An international study led by MSK investigators has found that liquid biopsies may improve survival in people with lung cancer.
  • These blood tests are easier for patients than more traditional tissue biopsies.

Moments after getting bad news about her lung cancer, Joyce Tyson got some good news. An experimental blood test called a liquid biopsy suggested a different treatment, which turned around her prognosis (outcome) for stage 4 lung cancer. Now that test can offer hope to more patients like Joyce, according to a new study published by researchers at Memorial Sloan Kettering Cancer Center (MSK).

A liquid biopsy works by detecting small amounts of cancer DNA floating in the blood that can reveal molecular changes in tumors, which in turn signal the drugs that are most likely to be effective.

Overcoming Lung Cancer Drug Resistance With Insights From a Liquid Biopsy

About a year into Joyce’s treatment for lung cancer, MSK medical oncologist Alexander Drilon, MD, delivered the message every patient dreads: The chemotherapy had stopped working. But there was hope. A liquid biopsy had revealed that Joyce’s lung cancer had a specific mutation in the RET gene, indicating it was likely to respond to a targeted drug. More than three years after starting that drug, the 82-year-old’s cancer is still stable.

“Our study showed there’s a real, significant lifesaving benefit from liquid biopsy,” says thoracic oncologist Bob Li, MD, PhD, MPH, who serves as Chief Scientific Officer of MSK Direct and senior author of the paper published online November 10, 2022, in Nature Medicine. “When we were able to match patients with targeted therapies, they survived much longer.”

It’s made all the difference for Joyce, who is also a survivor of Hodgkin lymphoma, diagnosed when she was a teenager in the 1950s. “The drug I’m getting now is so much better than chemotherapy,” she says.

Liquid Biopsies Help Patients by Matching Lung Tumors With Treatments

The Nature Medicine study followed 1,127 people who were being treated for non-small cell lung cancer and who had liquid biopsies. The test detected tumor DNA in the bloodstream of 723 patients. Of those, 255 had genomic alterations detected in their blood that could be matched with targeted therapies, and another 163 were matched with drugs based on their tissue analysis. The patients who got targeted therapies lived longer than those who could not be matched with specific drugs: They had a 37% reduction in mortality.

“The magnitude of benefit that patients get from targeted therapy is really huge,” says MSK medical oncology fellow Justin Jee, MD, PhD, the paper’s first author. “In the past, having high levels of tumor DNA in the blood was a sign of a worse prognosis, but now we can turn that around and use it to offer more effective treatments.”

Benefits of Liquid Biopsies Over Tissue Biopsies

In addition to helping find the right drug for someone’s cancer, liquid biopsies offer these benefits:

  • They require only a few vials of blood and are therefore easier for patients than traditional invasive biopsies, which require a trip to a procedural suite or operating room.
  • They can be performed frequently to determine whether a cancer is changing in response to treatment.
  • Their results are often available more quickly than those for tissue biopsies, allowing patients to start on new treatments sooner.

In fact, liquid biopsies are just as important as scans for detecting when a patient’s disease has started to come back or spread, says Dr. Jee, who holds a PhD in computational biology and conducted much of the trial’s data analysis.

Different Types of Liquid Biopsies

There are important differences among the kinds of liquid biopsies. There’s been a lot of attention on developing a blood test that would detect cancer in someone who has not previously been diagnosed, especially in people who are of high risk. But it’s important to note that while those tests are promising, they need more research before being used as a general cancer screening test.

Our study showed there's a real, significant lifesaving benefit from liquid biopsy.
Bob T. Li thoracic oncologist

For many years, Dr. Li’s research has proven the clinical utility of the kind of liquid biopsy that detects tumor mutations in people who have already been diagnosed with cancer, like Joyce.

Treating Lung Cancer With RET Gene Mutations

Joyce’s test revealed that her lung cancer carried a mutation in a gene called RET. This finding suggested that her tumors were likely to respond to a targeted drug called selpercatinib (Retevmo™). When she was first given selpercatinib in 2019, it was still experimental. Since then, it’s been approved by the U.S. Food and Drug Administration, based on research led by Dr. Drilon.

The magnitude of benefit that patients get from targeted therapy is really huge.
Justin Jee medical oncology fellow

Joyce has experienced no serious side effects from selpercatinib, which she takes as two pills, twice a day.

MSK Researchers Focus on Liquid Biopsies To Treat More Cancers

The Nature Medicine study focused mainly on a liquid biopsy test that was developed specifically for lung cancer. But more than 200 patients in the trial also had a kind of liquid biopsy that can detect molecular changes in other solid tumors in addition to lung cancer. This pan-cancer liquid biopsy test was developed at MSK and is called MSK-ACCESS®. The results from MSK-ACCESS were comparable to the lung cancer–specific test, the researchers found, which suggests that people with other kinds of cancer are likely to benefit from liquid biopsies as well.

Also, the clinical trial showed these tests can be used to guide treatment decisions for patients at other institutions in diverse communities, too. This study was a collaboration between investigators at MSK and GenesisCare, a community oncology practice with physicians affiliated with the University of Sydney in Australia. “Because these survival results were also seen in patients treated in a community oncology setting in Australia, this study demonstrates that liquid biopsies have the potential to benefit diverse patient populations,” Dr. Li says. “MSK’s research with international partnerships can help save lives all over the world.”

A Cancer Survivor Dedicated to Caring for Others

Back in Brooklyn, Joyce is living a full and satisfying life again. After retiring from a career in hospital administration and raising two children, Joyce has had a busy second act as a volunteer for organizations that provide services to children. Joyce has also been active in a support group for long-term survivors of Hodgkin lymphoma, offered through MSK’s Resources for Life After Cancer. She credits MSK’s Rehabilitation Medicine Service — including physiatrist Lisa Marie Ruppert, MD, and specialists in physical therapy and lymphedema — for helping her get back on her feet after treatment.

Joyce has been able to spend time with her son and daughter and four grandsons, who all live near her. She also keeps busy attending cultural events around the city. “I’ve had a lot of illness in my lifetime, but also a lot of success,” she says. “I turn 83 in January, and I’m proud that I’ve made it to where I am.”

The lung cancer–specific liquid biopsy test used in this study is made by Resolution Bioscience and Agilent Technologies, and employees of those companies participated in the research.

This work was supported by a grant from the Antidote Health Foundation for Cure of Cancer; National Institutes of Health grants T32-CA009207, CTSA UL1TR00457, P50 CA247749 01, and P30 CA008748; the Molecular Diagnostics Service in MSK’s Department of Pathology; and the Marie-Josée and Henry R. Kravis Center for Molecular Oncology at MSK.

Dr. Jee has a patent licensed by MDSeq Inc. Dr. Li has served as an uncompensated advisor and consultant to Amgen, AstraZeneca, Boehringer Ingelheim, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, and Lilly. He has received research grants to his institution from Amgen, AstraZeneca, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, Hengrui USA, and Lilly. He has received academic travel support from Amgen, Jiangsu Hengrui Medicine, and MORE Health. He is an inventor on two institutional patents at MSK (US62/685,057 and US62/514,661) and has intellectual property rights as a book author at Karger Publishers and Shanghai Jiao Tong University Press.