Yen-Ting Lin1, Chong-Jen Yu2, James Chih-Hsin Yang3, Jin-Yuan Shih4. 1. Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan. 2. Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan. 3. Department of Oncology, National Taiwan University Hospital and Graduate Institute of Oncology and Cancer Research Centre, College of Medicine, National Taiwan University, Taipei, Taiwan. 4. Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: jyshih@ntu.edu.tw.
Abstract
BACKGROUND: Secondary anaplastic lymphoma kinase (ALK) mutation may occur in patients with advanced ALK-positive non-small cell lung cancer treated with ALK inhibitors, but its nature is not well-known. PATIENTS AND METHODS: We analyzed tumor specimens after the failure of treatment with ALK inhibitor(s) (crizotinib, alectinib, and ceritinib) for secondary ALK kinase domain mutation, EGFR, K-ras, and PIK3CA mutations. The literature regarding acquired ALK-inhibitor(s) resistance was also reviewed. RESULTS: Among 59 patients who received ALK inhibitor(s) during the period of December 2010 to April 2015, 7 had re-biopsied tumor specimens for analyses following ALK inhibitor(s) failure. One had G1202R after crizotinib and alectinib failure, and 6 were wild type. No EGFR, K-ras, or PIK3CA mutations were found. In our review of the literature and taken together with our patients, 25 of the 88 (28%) patients with crizotinib failure had secondary ALK mutation; L1196M mutation was most common (n = 11). Patients with secondary ALK mutation other than L1196M had a longer progression-free survival after crizotinib than patients with L1196M (median, 12.0 vs. 7.0 months; P = .04). Of the 9 patients with alectinib failure, 5 had I1171 mutation and 2 had G1202R. Of the 11 patients with ceritinib failure, 2 had G1202R, 1 had F1174C, and 1 had both G1202R and F1174V. I1171 mutation, G1202R, and F1174 mutations were also found in crizotinib-failed patients. CONCLUSIONS: Some acquired ALK mutations may cause co-resistance to other ALK inhibitors. Re-biopsy for ALK mutation analysis might be suggested prior to choosing a second-line ALK inhibitor treatment.
BACKGROUND: Secondary anaplastic lymphoma kinase (ALK) mutation may occur in patients with advanced ALK-positive non-small cell lung cancer treated with ALK inhibitors, but its nature is not well-known. PATIENTS AND METHODS: We analyzed tumor specimens after the failure of treatment with ALK inhibitor(s) (crizotinib, alectinib, and ceritinib) for secondary ALK kinase domain mutation, EGFR, K-ras, and PIK3CA mutations. The literature regarding acquired ALK-inhibitor(s) resistance was also reviewed. RESULTS: Among 59 patients who received ALK inhibitor(s) during the period of December 2010 to April 2015, 7 had re-biopsied tumor specimens for analyses following ALK inhibitor(s) failure. One had G1202R after crizotinib and alectinib failure, and 6 were wild type. No EGFR, K-ras, or PIK3CA mutations were found. In our review of the literature and taken together with our patients, 25 of the 88 (28%) patients with crizotinib failure had secondary ALK mutation; L1196M mutation was most common (n = 11). Patients with secondary ALK mutation other than L1196M had a longer progression-free survival after crizotinib than patients with L1196M (median, 12.0 vs. 7.0 months; P = .04). Of the 9 patients with alectinib failure, 5 had I1171 mutation and 2 had G1202R. Of the 11 patients with ceritinib failure, 2 had G1202R, 1 had F1174C, and 1 had both G1202R and F1174V. I1171 mutation, G1202R, and F1174 mutations were also found in crizotinib-failed patients. CONCLUSIONS: Some acquired ALK mutations may cause co-resistance to other ALK inhibitors. Re-biopsy for ALK mutation analysis might be suggested prior to choosing a second-line ALK inhibitor treatment.
Authors: Jason N Rosenbaum; Ryan Bloom; Jason T Forys; Jeff Hiken; Jon R Armstrong; Julie Branson; Samantha McNulty; Priya D Velu; Kymberlie Pepin; Haley Abel; Catherine E Cottrell; John D Pfeifer; Shashikant Kulkarni; Ramaswamy Govindan; Eric Q Konnick; Christina M Lockwood; Eric J Duncavage Journal: Mod Pathol Date: 2018-01-12 Impact factor: 7.842
Authors: Alessandro Russo; Andrés F Cardona; Christian Caglevic; Paolo Manca; Alejandro Ruiz-Patiño; Oscar Arrieta; Christian Rolfo Journal: Transl Lung Cancer Res Date: 2020-12