Kenichiro Kudo1,2, Kazuya Nishii2,3, Go Makimoto2,3, Nobuhisa Ishikawa4, Yukari Tsubata5, Masahiro Kodani6, Nobukazu Fujimoto7, Masahiro Yamasaki8, Tetsuya Kubota9, Nagio Takigawa10, Kazunori Fujitaka11, Nobuhiro Kanaji12, Takuo Shibayama1, Junko Itano3, Chihiro Ando3, Katsuyuki Hotta13,14, Katsuyuki Kiura3. 1. Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center, Okayama, Japan. 2. Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center, Iwakuni, Japan. 3. Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan. 4. Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan. 5. Division of Medical Oncology and Respiratory Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine, Izumo, Shimane, Japan. 6. Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, Japan. 7. Department of Respiratory Medicine, Okayama Rosai Hospital, Okayama, Japan. 8. Department of Respiratory Medicine, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, Japan. 9. Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University, Kochi, Japan. 10. Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan. 11. Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. 12. Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kida, Kagawa, Japan. 13. Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan. khotta@okayama-u.ac.jp. 14. Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan. khotta@okayama-u.ac.jp.
Abstract
PURPOSE: Osimertinib is still essential for the treatment of epidermal growth factor receptor (EGFR)-T790M-positive non-small-cell lung cancer (NSCLC) even in a relapsed setting, which suggests the importance of rebiopsy. The clinical value of repeat rebiopsy in patients with NSCLC who are T790M-negative on a first rebiopsy remains unclear. In this study, we examined the status of the first rebiopsy and evaluated the frequency of repeat rebiopsy of T790M-negative tumors detected by the first rebiopsy. METHODS: We reviewed 144 patients with NSCLC with major EGFR mutations, but not T790M, who received first- or second-generation EGFR tyrosine kinase inhibitors (TKIs), registered in the prospective, umbrella-type lung cancer patient registry (CS-Lung-003). RESULTS: Overall, 63 patients (44%) underwent the first rebiopsy. In the first rebiopsy, 51 (81%) and 12 (19%) of 63 underwent histological/cytological rebiopsy and liquid biopsy with the blood sampling, respectively. In the repeat rebiopsy, 23 (85%) and 4 (15%) of 27 underwent histological/cytological rebiopsy and liquid biopsy, respectively. The most frequently rebiopsied site was a pulmonary lesion (n = 24, 38.7%). Overall, 29 (46.0%) of 63 patients harbored the T790M mutation. Interestingly, a high detection rate of cancer cells did not necessarily indicate a high detection rate of the T790M mutation (p < 0.01). Among 34 patients with T790M-negative tumors confirmed on the first rebiopsy, 20 (58.8%) underwent repeat rebiopsies following interval therapy, revealing that seven (36.8%) had T790M-positive tumors. Osimertinib yielded median progression-free survival of 11.8 and 16.2 months in patients with the 790M mutation detected by the first rebiopsy and repeat rebiopsy, respectively. CONCLUSION: In our prospective cohort, the T790M mutation was detected in 46% of patients who underwent the first rebiopsy. Repeat rebiopsy may increase the ability to detect the T790M mutation positivity rate.
PURPOSE: Osimertinib is still essential for the treatment of epidermal growth factor receptor (EGFR)-T790M-positive non-small-cell lung cancer (NSCLC) even in a relapsed setting, which suggests the importance of rebiopsy. The clinical value of repeat rebiopsy in patients with NSCLC who are T790M-negative on a first rebiopsy remains unclear. In this study, we examined the status of the first rebiopsy and evaluated the frequency of repeat rebiopsy of T790M-negative tumors detected by the first rebiopsy. METHODS: We reviewed 144 patients with NSCLC with major EGFR mutations, but not T790M, who received first- or second-generation EGFR tyrosine kinase inhibitors (TKIs), registered in the prospective, umbrella-type lung cancer patient registry (CS-Lung-003). RESULTS: Overall, 63 patients (44%) underwent the first rebiopsy. In the first rebiopsy, 51 (81%) and 12 (19%) of 63 underwent histological/cytological rebiopsy and liquid biopsy with the blood sampling, respectively. In the repeat rebiopsy, 23 (85%) and 4 (15%) of 27 underwent histological/cytological rebiopsy and liquid biopsy, respectively. The most frequently rebiopsied site was a pulmonary lesion (n = 24, 38.7%). Overall, 29 (46.0%) of 63 patients harbored the T790M mutation. Interestingly, a high detection rate of cancer cells did not necessarily indicate a high detection rate of the T790M mutation (p < 0.01). Among 34 patients with T790M-negative tumors confirmed on the first rebiopsy, 20 (58.8%) underwent repeat rebiopsies following interval therapy, revealing that seven (36.8%) had T790M-positive tumors. Osimertinib yielded median progression-free survival of 11.8 and 16.2 months in patients with the 790M mutation detected by the first rebiopsy and repeat rebiopsy, respectively. CONCLUSION: In our prospective cohort, the T790M mutation was detected in 46% of patients who underwent the first rebiopsy. Repeat rebiopsy may increase the ability to detect the T790M mutation positivity rate.
Authors: Pasi A Jänne; James Chih-Hsin Yang; Dong-Wan Kim; David Planchard; Yuichiro Ohe; Suresh S Ramalingam; Myung-Ju Ahn; Sang-We Kim; Wu-Chou Su; Leora Horn; Daniel Haggstrom; Enriqueta Felip; Joo-Hang Kim; Paul Frewer; Mireille Cantarini; Kathryn H Brown; Paul A Dickinson; Serban Ghiorghiu; Malcolm Ranson Journal: N Engl J Med Date: 2015-04-30 Impact factor: 91.245
Authors: Jacob J Chabon; Andrew D Simmons; Alexander F Lovejoy; Mohammad S Esfahani; Aaron M Newman; Henry J Haringsma; David M Kurtz; Henning Stehr; Florian Scherer; Chris A Karlovich; Thomas C Harding; Kathleen A Durkin; Gregory A Otterson; W Thomas Purcell; D Ross Camidge; Jonathan W Goldman; Lecia V Sequist; Zofia Piotrowska; Heather A Wakelee; Joel W Neal; Ash A Alizadeh; Maximilian Diehn Journal: Nat Commun Date: 2016-06-10 Impact factor: 14.919