Further Analysis Needed to Incorporate Liquid Biopsy in the Community Setting

Potential benefits of incorporating liquid biopsy into community-based oncology practices include early signal-based therapeutic matching, referral to appropriate signal-based clinical trials, and improved survival outcomes, according to retrospective study findings published in The Oncologist.

This study was conducted using charts from 178 patients receiving care for advanced solid malignancies at Cancer Center of Kansas, and a liquid-based assay was used to evaluate these malignancies between December 2018 and 2019. Liquid biopsy has a favorable utility profile in that it is less invasive vs tissue-based biopsy and next-generation sequencing of circulating tumor DNA has higher sensitivity, they highlighted.

There was a follow-up at 1 year to evaluate treatment assignment and survival. Study end points included progression-free survival (PFS) in cases of lung, breast, and colorectal cancer and overall survival (OS) in patients with lung, breast, and colorectal cancer.

“Liquid biopsy testing offers a significant potential in selecting signal-matched therapies for advanced solid malignancies,” the authors wrote. “The feasibility of liquid biopsy testing in a community-based oncology practice, and its actual impact on selecting signal-matched therapies, and subsequent survival effects have not previously been reported.”

Among the 178 patients tested, 98% tested had a new diagnosis, advanced cancer, or recurrent disease with not enough tissue for testing; the remaining 2% were tested following first-line treatment failure. Most patients also had stage IIIb disease and above, the mean age at diagnosis was 65 years, and the most common cancers were lung (50.56%), breast (17.42%), and colon (7.87%).

Seventy-nine percent of the study cohort (n = 140) tested positive for mutations, with these individuals subdivided into patients with actionable mutations with an FDA-approved targeted treatment (n = 32), actionable mutations with an FDA approval used off label (n = 73), and unactionable mutations (n = 35).

Overall, 481 genetic alterations were identified, with the mean per liquid biopsy being 3.1 (2.14). The highest average per test were seen among colon cancer (4.36), breast cancer (2.97), prostate cancer (2.73), and lung cancer (2.59), and the 3 cancers with the most detected somatic mutations overall were lung, breast, and colon, respectively.

Of the 481 total alterations, 95% were actionable. Within this group, the most common altered genes were TP53 (32.17%), PIK3CA (8.53%), EGFR (7.66%), and KRAS (7.22%).

Ninety-five percent of those who tested positive for mutations were candidates for targeted treatment (n = 135), with most receiving an unmatched therapy. Further, for those designated candidates for FDA-approved treatments, just half actually received a targeted treatment; close to 7% received a treatment off label; and 10% were referred to signal-based clinical trials. The most common reason for not receiving a signal-matched treatment among participants with 1 or more actionable mutations was treatment availability.

Following a subanalysis of survival rates at 1 year seen among patients with lung, breast, or colon cancer who received a matched therapy following liquid biopsy and those who did not, these results were seen:

• The matched group had more patients with breast cancer vs the unmatched group: 27.3% vs 15.9%
• Fewer patients with lung cancer and colorectal cancer were seen in the matched vs unmatched group: 63.6% vs 72.7% and 9.1% vs 11.4%, respectively
• Median overall survival (mOS) was 13 (range, 11.4-14.6) months
• The matched vs the unmatched cohort had a longer mOS (15 vs 13 months) and a longer PFS (12 vs 5 months)
• Statistically significant differences were not seen in either OS or PFS among the patients who received matched treatment and had higher or lower matching scores (ie, the higher the score, the better the treatment match, according to the authors)

The study authors highlight that their findings are important because their patients were tested up front for alterations, prior to treatment, vs having already undergone several lines of treatment and the results echo previous research. In addition, their data bear out that combining matched therapies for use in patients with several actionable mutations is a potential treatment pathway.

“In fact,” they wrote, “other studies have also suggested that treatment with single-agent matched therapy resulted in significantly lower response rates compared to combination therapy.”

Still, large prospective controlled clinical trials are needed to confirm their findings and to investigate if providing community-based liquid-biopsy testing facilitates betterment of quality of life, early cancer detection, disease monitoring, and cost benefits compared with tissue-based biopsy.

Reference

Choucair K, Mattar BI, Truong QV, et al.Liquid biopsy-based precision therapy in patients with advanced solid tumors: a real-world experience from a community-based oncology practice. The Oncologist. Published online February 19, 2022. doi:10.1093/oncolo/oyac007