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A phase II, multicenter, two cohort study of 160 mg osimertinib in EGFR T790M-positive non-small-cell lung cancer patients with brain metastases or leptomeningeal disease who progressed on prior EGFR TKI therapy.
Ann Oncol. 2020 Jul 05 [Online ahead of print]AO

Abstract

BACKGROUND

Up to 40% of patients with non-small-cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations treated with EGFR tyrosine kinase inhibitors (TKIs) present with disease progression in the central nervous system (CNS), either as brain metastases (BM) or leptomeningeal metastases (LM). Osimertinib (80 mg), a third-generation, irreversible, oral EGFR TKI, has shown efficacy in active CNS metastases. However, efficacy of osimertinib 160 mg in BM or LM is unclear.

PATIENTS AND METHODS

This prospective, single-arm, two cohort study evaluated the efficacy of osimertinib 160 mg in T790M-positive BM or LM NSCLC patients who progressed on prior EGFR TKI (NCT03257124) treatment. The primary end points were objective response rate (ORR) (H1 = 30%) for the BM cohort and overall survival (OS) (H1 = 5 months) for the LM cohort.

RESULTS

The median follow-up duration was 10.1 months and 9.6 months for the BM and LM cohorts, respectively. In the BM cohort, intracranial ORR and disease control rate were 55.0% and 77.5%, respectively. The median progression-free survival (PFS) was 7.6 months [95% confidence interval (CI) 5.0-16.6]; the median OS was 16.9 months [95% CI 7.9-not reached (NR)]. In the LM cohort, intracranial disease control rate was 92.5% and complete response rate was 12.5%. The median OS was 13.3 months (95% CI 9.1-NR); the median PFS was 8.0 months (95% CI 7.2-NR). Subgroup analyses based on previous exposure to T790M-targeting agents, including osimertinib 80 mg or other third-generation EGFR TKIs, showed no difference in PFS in both the BM (n = 18, P = 0.39) and LM (n = 17, P = 0.85) cohorts. Previous radiotherapy favored PFS in the BM cohort (hazard ratio 0.42, P = 0.04). The most common adverse events were decreased appetite, diarrhea, and skin rash; however, most were grade 1-2.

CONCLUSION

Thus, osimertinib 160 mg demonstrated promising ORR and survival benefit with a tolerable safety profile in EGFR T790M-positive NSCLC patients with CNS metastasis who progressed on prior EGFR TKIs.

Authors+Show Affiliations

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea.Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.The Catholic University of Korea Seoul St. Mary's Hospital, Seoul, Korea.Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.Chungbuk National University College of Medicine, Cheongju, Korea.Gachon University Gil Hospital, Incheon, Korea.Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Electronic address: silkahn@skku.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32634610

Citation

Park, S, et al. "A Phase II, Multicenter, Two Cohort Study of 160 Mg Osimertinib in EGFR T790M-positive Non-small-cell Lung Cancer Patients With Brain Metastases or Leptomeningeal Disease Who Progressed On Prior EGFR TKI Therapy." Annals of Oncology : Official Journal of the European Society for Medical Oncology, 2020.
Park S, Lee MH, Seong M, et al. A phase II, multicenter, two cohort study of 160 mg osimertinib in EGFR T790M-positive non-small-cell lung cancer patients with brain metastases or leptomeningeal disease who progressed on prior EGFR TKI therapy. Ann Oncol. 2020.
Park, S., Lee, M. H., Seong, M., Kim, S. T., Kang, J. H., Cho, B. C., Lee, K. H., Cho, E. K., Sun, J. M., Lee, S. H., Ahn, J. S., Park, K., & Ahn, M. J. (2020). A phase II, multicenter, two cohort study of 160 mg osimertinib in EGFR T790M-positive non-small-cell lung cancer patients with brain metastases or leptomeningeal disease who progressed on prior EGFR TKI therapy. Annals of Oncology : Official Journal of the European Society for Medical Oncology. https://doi.org/10.1016/j.annonc.2020.06.017
Park S, et al. A Phase II, Multicenter, Two Cohort Study of 160 Mg Osimertinib in EGFR T790M-positive Non-small-cell Lung Cancer Patients With Brain Metastases or Leptomeningeal Disease Who Progressed On Prior EGFR TKI Therapy. Ann Oncol. 2020 Jul 5; PubMed PMID: 32634610.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A phase II, multicenter, two cohort study of 160 mg osimertinib in EGFR T790M-positive non-small-cell lung cancer patients with brain metastases or leptomeningeal disease who progressed on prior EGFR TKI therapy. AU - Park,S, AU - Lee,M-H, AU - Seong,M, AU - Kim,S T, AU - Kang,J-H, AU - Cho,B C, AU - Lee,K H, AU - Cho,E K, AU - Sun,J-M, AU - Lee,S-H, AU - Ahn,J S, AU - Park,K, AU - Ahn,M-J, Y1 - 2020/07/05/ PY - 2020/03/26/received PY - 2020/06/19/revised PY - 2020/06/22/accepted PY - 2020/7/8/pubmed PY - 2020/7/8/medline PY - 2020/7/8/entrez KW - EGFR T790M KW - brain metastases KW - leptomeningeal disease KW - non-small-cell lung cancer KW - osimertinib JF - Annals of oncology : official journal of the European Society for Medical Oncology JO - Ann. Oncol. N2 - BACKGROUND: Up to 40% of patients with non-small-cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations treated with EGFR tyrosine kinase inhibitors (TKIs) present with disease progression in the central nervous system (CNS), either as brain metastases (BM) or leptomeningeal metastases (LM). Osimertinib (80 mg), a third-generation, irreversible, oral EGFR TKI, has shown efficacy in active CNS metastases. However, efficacy of osimertinib 160 mg in BM or LM is unclear. PATIENTS AND METHODS: This prospective, single-arm, two cohort study evaluated the efficacy of osimertinib 160 mg in T790M-positive BM or LM NSCLC patients who progressed on prior EGFR TKI (NCT03257124) treatment. The primary end points were objective response rate (ORR) (H1 = 30%) for the BM cohort and overall survival (OS) (H1 = 5 months) for the LM cohort. RESULTS: The median follow-up duration was 10.1 months and 9.6 months for the BM and LM cohorts, respectively. In the BM cohort, intracranial ORR and disease control rate were 55.0% and 77.5%, respectively. The median progression-free survival (PFS) was 7.6 months [95% confidence interval (CI) 5.0-16.6]; the median OS was 16.9 months [95% CI 7.9-not reached (NR)]. In the LM cohort, intracranial disease control rate was 92.5% and complete response rate was 12.5%. The median OS was 13.3 months (95% CI 9.1-NR); the median PFS was 8.0 months (95% CI 7.2-NR). Subgroup analyses based on previous exposure to T790M-targeting agents, including osimertinib 80 mg or other third-generation EGFR TKIs, showed no difference in PFS in both the BM (n = 18, P = 0.39) and LM (n = 17, P = 0.85) cohorts. Previous radiotherapy favored PFS in the BM cohort (hazard ratio 0.42, P = 0.04). The most common adverse events were decreased appetite, diarrhea, and skin rash; however, most were grade 1-2. CONCLUSION: Thus, osimertinib 160 mg demonstrated promising ORR and survival benefit with a tolerable safety profile in EGFR T790M-positive NSCLC patients with CNS metastasis who progressed on prior EGFR TKIs. SN - 1569-8041 UR - https://www.unboundmedicine.com/medline/citation/32634610/A_phase_II_multicenter_two_cohort_study_of_160_mg_osimertinib_in_EGFR_T790M_positive_non_small_cell_lung_cancer_patients_with_brain_metastases_or_leptomeningeal_disease_who_progressed_on_prior_EGFR_TKI_therapy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0923-7534(20)39927-0 DB - PRIME DP - Unbound Medicine ER -
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