Liquid Biopsies Could Guide NSCLC Treatment

A liquid biopsy may be able to predict the efficacy of EGFR-targeted tyrosine kinase inhibitors (TKIs) in patients with non–small cell lung cancer (NSCLC), according to the results of a new study. The presence or absence of EGFR-activating mutations both at baseline and during treatment were correlated with outcomes.

“Although monitoring of EGFR-activating mutations in plasma has been suggested to be informative for prediction of the efficacy of EGFR-TKIs, its usefulness has remained unclear,” wrote study authors led by Eiji Iwama, MD, PhD, of Kyushu University in Fukuoka, Japan. “[A] liquid biopsy approach can be performed in a noninvasive and repeated manner, with analysis of the cell-free DNA also having the potential to provide insight into the extent of intratumoral heterogeneity.”

The authors conducted a study of 100 patients with NSCLC; plasma samples were collected prospectively, and they were analyzed for EGFR-activating mutations with droplet digital polymerase chain reaction, as well as for other somatic alterations using next-generation sequencing. The results of the study were published online ahead of print on September 10 in Cancer.

A total of 87 patients were EGFR-TKI-naive. The median age in the study was 69 years, and the cohort was approximately evenly divided between men and women. A majority of patients were never smokers (57.0%), while 34.0% were former smokers and 9.0% were current smokers. Most patients had stage IV disease (92.0%), and the most common metastatic sites included the brain, bones, lungs, and liver.

The median follow-up time was 16.3 months in the EGFR-TKI-naive patients and 7.7 months in the 13 patients who had received EGFR-TKI therapy. The median progression-free survival (PFS) was significantly shorter in the naive patients with EGFR-activating mutations detected in plasma at baseline than in those without such mutations, at 7.9 months compared with 19.0 months (P < 0.001). PFS was significantly longer in patients who were initially positive for the mutations, but then became negative at 12 or 24 weeks when compared to those who remained positive.

Patients who had an increase in the number of alleles positive for EGFR-activating mutations in plasma during the course of treatment were more likely to have disease progression, with a hazard ratio of 4.72 (95% CI, 2.07-10.79; P< 0.001) for those showing such an increase within 36 weeks. 

“Our results show that the presence or an increase in the number of alleles positive for EGFR‐activating mutations in cfDNA before or during EGFR‐TKI treatment is a negative predictive biomarker for such treatment,” the authors concluded. “We also reveal an increase in the number of somatic alterations after targeted therapy compared with baseline, suggesting the potential of liquid biopsy for elucidation of clonal evolution of tumors during targeted therapy.”

In an accompanying editorial, authors led by Umberto Malapelle, PhD, of Univrsity Federico II of Naples in Italy, wrote that this represents “an important step forward to implement liquid biopsy.” The study’s results indicatie the ability to use real-time monitoring with next-generation sequencing at serial time points during treatment “can lead to a capitalization of precision medicine armamentarium to improve the overall survival of our cancer patients and could represent a new standard of care in NSCLC patients if confirmed in larger prospective studies in the future.”

References:

IWAMA, E., SAKAI, K., HIDAKA, N., INOUE, K., FUJII, A., NAKAGAKI, N., OTA, K., TOYOZAWA, R., AZUMA, K., NAKATOMI, K., HARADA, T., HISASUE, J., SAKATA, S., SHIMOSE, T., KISHIMOTO, J., NAKANISHI, Y., NISHIO, K. AND OKAMOTO, I.
Longitudinal monitoring of somatic genetic alterations in circulating cell‐free DNA during treatment with epidermal growth factor receptor–tyrosine kinase inhibitors
In-text: (Iwama et al., 2019)

Your Bibliography: Iwama, E., Sakai, K., Hidaka, N., Inoue, K., Fujii, A., Nakagaki, N., Ota, K., Toyozawa, R., Azuma, K., Nakatomi, K., Harada, T., Hisasue, J., Sakata, S., Shimose, T., Kishimoto, J., Nakanishi, Y., Nishio, K. and Okamoto, I. (2019). Longitudinal monitoring of somatic genetic alterations in circulating cell‐free DNA during treatment with epidermal growth factor receptor–tyrosine kinase inhibitors. Cancer.