Liquid Biopsy Shortens Time to NSCLC Treatment

Neil Osterweil

August 04, 2023

Testing blood samples from patients with advanced non–small cell lung cancer (NSCLC) for tumor mutations prior to their receiving a confirmed diagnosis via tissue biopsy can help shorten the time to treatment, investigators found.

Patients who underwent liquid biopsy with next-generation sequencing (NGS) as well as standard tissue biopsy received treatment within a median of 39 days, vs 62 days for those diagnosed through standard tissue biopsy alone — a 23-day head start. Of the 90 patients diagnosed with advanced NSCLC in the liquid biopsy group, 23% started targeted therapy on the basis of their plasma ctDNA findings alone; the median time to treatment was 27 days.

"These results suggest the clinical utility of adding plasma ctDNA testing before tissue biopsy or confirmed cancer diagnosis to the standard diagnostic workup of patients with suspected advanced lung cancer," the researchers, led by Miguel García-Pardo, MD, from the Princess Margaret Cancer Centre in Toronto, Canada, write. "Although we believe this is a promising strategy to improve the diagnostic journey and treatment decision-making for patients with advanced NSCLC, the effect of this approach on clinically meaningful outcomes, such as quality of life, survival, and cost-effectiveness, still needs to be demonstrated."

The study was published online July 25 in JAMA Network Open.

Molecular testing of tumor tissue remains the standard for diagnosing and genotyping NSCLC, but it can be a time-consuming process. Liquid biopsy has emerged as a complement to tissue biopsy for advanced NSCLC, but the optimal strategy for incorporating liquid biopsy into the diagnostic workup remains unclear. The current study explored whether ctDNA genotyping of patients with suspected advanced lung cancer can shorten time to treatment.

In the nonrandomized trial, Garcia-Pardo and colleagues assessed time to treatment for patients referred for investigation and diagnosis of lung cancer following radiologic evidence suggesting advanced NSCLC.

Patients were eligible to participate if there was radiologic evidence of unresectable stage III or IV lung cancer, if 1 cm or more of disease was detected by CT, or if a diagnostic tissue biopsy was planned or had been performed without the patient having as yet been diagnosed with NSCLC.

All of the 150 patients enrolled in the liquid biopsy cohort underwent blood draws for ctDNA analysis with NGS; 145 also underwent standard diagnostic tissue biopsy. Among these patients, 90 received a tissue-confirmed diagnosis of advanced nonsquamous NSCLC; for 74 of these patients, tissue NGS was completed.

The reference cohort included 89 patients, all of whom underwent tissue molecular testing only.

Overall, Garcia-Pardo and colleagues found that the median time to treatment was 39 days (interquartile range [IQR], 27–52 days), compared with 62 days (IQR, 44–82 days) for the reference cohort (P < .001). Some of this difference can be attributed to the median time to tissue biopsy in both groups — 12 days for the liquid biopsy cohort and 24 for the reference cohort.

In the liquid biopsy group, the median turnaround time from plasma sample collection to genotyping results was 7 days, vs 23 days for tissue NGS (P < .001).

Of the 90 patients diagnosed with advanced nonsquamous NSCLC, 21 (23%) started targeted therapy before tissue NGS results were available; for these patients, the median time to treatment was shorter, at 27 days. Among the patients in the liquid biopsy group for whom therapy did not begin until tissue NGS results were available, the median time to treatment was 41 days.

Overall, 11 patients (12%) had actionable alterations that were identified only via plasma ctDNA testing. Seven patients had actionable alterations that were identified in tissue only.

"Complementing standard tissue testing with plasma testing before diagnosis could increase access to precision medicine and may improve patient outcomes," the authors conclude.

Roy S. Herbst, MD, PhD, deputy director of the Yale Cancer Center in New Haven, Connecticut, who was not involved in the study, agreed, noting that "the last thing you want, in this era where you have nine different targeted therapies for lung cancer, or even more, is to give the wrong drug to the wrong patient or to give them chemotherapy or immunotherapy when they have a targetable abnormality."

Time to treatment can make a difference. For some patients in the trial, appropriate therapy began as early as 27 days after blood collection for ctDNA, an especially important consideration for patients with NSCLC of aggressive histology, Herbst noted.

"With EGFR mutations, within 3 weeks or even days, sometimes you'll see patients starting to present with symptoms, so time does matter," said Herbst, who is also chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital.

Although the sensitivity of liquid biopsy continues to improve, and it's possible to diagnosis some cases using ctDNA, fluorescent in situ hybridization is still required if liquid biopsy results are negative, Herbst noted.

García-Pardo and colleagues highlight several limitations to their study, including its single-group prospective design. The authors also note that although patients were selected by a multidisciplinary team on the basis of radiologic evidence for advanced lung cancer, only 70% of the patients had biopsy-proven advanced NSCLC, while 30% had other diagnoses or no malignant lesions.

"These results reinforce the need for tissue biopsy for lung cancer diagnosis and pathologic subtyping: plasma first does not mean plasma only," the study team said.

The study was supported by the Lung Health Foundation Breathe Better Breathing as One Grant Award Program, the Princess Margaret Cancer Foundation, the Division of Medical Oncology/Hematology Fellowship Award, and the Merck Canada/MaRS Discovery District Lung Cancer Innovation Challenge. Liquid biopsy testing was obtained free of charge through Inivata Inc. Garci-Pardo disclosed no conflict of interest. Multiple co-authors reported relationships with industry. Herbst has consulted for, has received institutional research support from, and owns stock options from several companies not related to those involved in the study.

JAMA Netw Open. Published online July 25, 2023. Full text

Neil Osterweil, an award-winning medical journalist, is a long-standing and frequent contributor to Medscape.

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