|The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Liquid biopsies can match non-small cell lung cancer (NSCLC) patients to life-prolonging targeted therapy and have prognostic importance. Targeted therapy has transformed the treatment landscape of NSCLC and fundamentally made it possible, by next-generation sequencing of tissue, to match patients to therapies that prolong overall survival (OS).
“Now that we have the ability to sequence DNA in plasma, the question is ‘What is the extent these assays can replace or supplement tissue sequencing?’ Early studies have found that patients can be matched to treatment through plasma sequencing, and patients have a radiographic initial response,” stated Justin Jee, MD, of Memorial Sloan Kettering Cancer Center in New York, New York, during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Plasma sequencing can overcome the challenge of tissue sequencing with faster turnaround time, he noted.
To understand the relationships across circulating tumor DNA (ctDNA), matched therapy, and OS, Dr Jee and colleagues conducted a large, prospective cohort study for 4 years that included 1002 patients with NSCLC who were a median age of 68 years (ClinicalTrials.gov identifier: NCT01775072). Adults with metastatic or recurrent NSCLC were eligible if they had no known driver mutation or a known driver with progression following targeted therapy. Patients were enrolled starting on October 21, 2016. Dr Jee presented study data from a November 1, 2020, snapshot.
A total of 348 patients were treated with targeted therapy, 220 of whom were ctDNA-matched and 128 who were tissue-matched. Targetable alterations were detected in ctDNA in half of these patients. Target gene proportions were similar between the 2 groups.
Targeted therapy was associated with better survival with both ctDNA (hazard ratio [HR], 0.63) and tissue-only matches (HR, 0.46). These benefits persisted across multiple subgroups. ctDNA alterations themselves were associated with worse survival (HR, 2.2; 95% CI, 1.8-2.8), in a manner that scaled with allele fraction and burden.
“The presence of ctDNA is a poor prognostic sign,” Dr Jee explained. “If you sequence the ctDNA and match it to targeted therapy, that can be life-prolonging.”
“Our large, prospective cohort shows 22% of patients matched to targeted therapy by ctDNA, and an additional 13% were matched by tissue only,” Dr Jee said in closing. “ctDNA alterations are independently associated with worse survival, even accounting for clinical and radiographic features. ctDNA-only alterations are especially associated with worse survival and likely represent genomic heterogeneity, although some of these are actionable. Studies using ctDNA to match targeted therapy should account for lower baseline survival.”
Future research will include an additional cohort fully enrolled in a community oncology setting in Sydney, Australia, for real-world validation.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Read more of Cancer Therapy Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.
Jee J, Lebow ES, Murciano-Goroff YR, et al. Overall survival with circulating tumor DNA-guided therapy in advanced non-small cell lung cancer. J Clin Oncol. 2021;39:(suppl 15; abstr 9009). doi:10.1200/JCO.2021.39.15_suppl.9009