Eiji Iwama1, Kazuko Sakai2, Noriko Hidaka1, Koji Inoue3, Akiko Fujii4, Noriaki Nakagaki5, Keiichi Ota6, Ryo Toyozawa7, Koichi Azuma8, Keita Nakatomi9, Taishi Harada10, Junko Hisasue11, Shinya Sakata12, Takayuki Shimose13, Junji Kishimoto14, Yoichi Nakanishi1, Kazuto Nishio2, Isamu Okamoto1. 1. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 2. Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan. 3. Department of Respiratory Medicine, Kitakyushu Municipal Medical Center, Kita-Kyushu, Japan. 4. Department of Respiratory Medicine, Koga Hospital 21, Kurume, Japan. 5. Department of Respiratory Medicine, Steel Memorial Yawata Hospital, Kita-Kyushu, Japan. 6. Department of Respiratory Medicine, National Hospital Organization Fukuoka-higashi Medical Center, Fukuoka-Koga, Japan. 7. Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan. 8. Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan. 9. Department of Respiratory Medicine, Kyushu Chuo Hospital, Fukuoka, Japan. 10. Department of Respiratory Medicine, Japan Community Healthcare Organization Kyushu Hospital, Kita-Kyushu, Japan. 11. Department of Respiratory Medicine, Hara Sanshin Hospital, Fukuoka, Japan. 12. Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. 13. Clinical Research Support Center Kyushu, Fukuoka, Japan. 14. Department of Research and Development of Next Generation Medicine, Kyushu University, Fukuoka, Japan.
Abstract
BACKGROUND: The aim of this study was to evaluate the potential of liquid biopsy for prediction of the efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment and for assessment of the changes in genetic alterations during such treatment. METHODS: Plasma samples were prospectively collected from non-small cell lung cancer patients with EGFR-activating mutations during EGFR-TKI treatment until disease progression and were analyzed for such mutations with droplet digital polymerase chain reaction and for other somatic alterations with next-generation sequencing. RESULTS: One hundred patients, including 87 who were EGFR-TKI naïve, were enrolled. Median progression-free survival was significantly shorter for EGFR-TKI-naïve patients with EGFR-activating mutations detected in plasma at baseline than for those without them (7.9 vs 19.0 months; P < .001), with the values being significantly longer for initially positive patients who became negative for these mutations at 12 or 24 weeks than for those who remained positive. An increase in the number of alleles positive for EGFR-activating mutations in plasma during treatment was associated with disease progression, with a hazard ratio of 4.72 (95% CI, 2.07-10.79; P < .001) for EGFR-TKI-naïve patients showing an increase within 36 weeks. For 55 patients with available samples, the total number of somatic alterations (other than activating mutations or T790M of EGFR) in plasma was higher at disease progression than at baseline (33 vs 19; P = 0.04). CONCLUSION: Liquid biopsy shows potential for prediction of EGFR-TKI efficacy and elucidation of clonal tumor evolution during targeted therapy.
BACKGROUND: The aim of this study was to evaluate the potential of liquid biopsy for prediction of the efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment and for assessment of the changes in genetic alterations during such treatment. METHODS: Plasma samples were prospectively collected from non-small cell lung cancerpatients with EGFR-activating mutations during EGFR-TKI treatment until disease progression and were analyzed for such mutations with droplet digital polymerase chain reaction and for other somatic alterations with next-generation sequencing. RESULTS: One hundred patients, including 87 who were EGFR-TKI naïve, were enrolled. Median progression-free survival was significantly shorter for EGFR-TKI-naïve patients with EGFR-activating mutations detected in plasma at baseline than for those without them (7.9 vs 19.0 months; P < .001), with the values being significantly longer for initially positive patients who became negative for these mutations at 12 or 24 weeks than for those who remained positive. An increase in the number of alleles positive for EGFR-activating mutations in plasma during treatment was associated with disease progression, with a hazard ratio of 4.72 (95% CI, 2.07-10.79; P < .001) for EGFR-TKI-naïve patients showing an increase within 36 weeks. For 55 patients with available samples, the total number of somatic alterations (other than activating mutations or T790M of EGFR) in plasma was higher at disease progression than at baseline (33 vs 19; P = 0.04). CONCLUSION: Liquid biopsy shows potential for prediction of EGFR-TKI efficacy and elucidation of clonal tumor evolution during targeted therapy.
Authors: Diego Cortinovis; Umberto Malapelle; Fabio Pagni; Alessandro Russo; Giuseppe Luigi Banna; Elisa Sala; Christian Rolfo Journal: Transl Lung Cancer Res Date: 2021-07