Daria Gaut1, Myung Shin Sim2, Yuguang Yue2, Brian R Wolf3, Phillip A Abarca3, James M Carroll3, Jonathan W Goldman3, Edward B Garon3. 1. Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA. Electronic address: dgaut@mednet.ucla.edu. 2. Division of General Internal Medicine and Health Services Research, Department of Medicine Statistics Core, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA. 3. Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
Abstract
BACKGROUND: The secondary T790M mutation accounts for more than 50% of acquired tyrosine kinase inhibitor (TKI) resistance in patients with EGFR-mutated non-small-cell lung cancer (NSCLC). Recent reports suggest this resistance mutation may be more common among patients with longer progression-free survival (PFS) on first-line TKI therapy, but much is still unknown. MATERIALS AND METHODS: Our group collected medical records from patients who underwent a biopsy for T790M mutation testing while screening for clinical trials involving the drug rociletinib (CO-1686), a T790M mutation-specific TKI. Medical records were retrospectively analyzed for demographic data, PFS, and best response to previous therapies. RESULTS: Our patient cohort included 69 T790M+ patients and 28 T790M- patients. Patients who later developed a T790M mutation had a longer PFS on first-line TKI therapy (12.0 vs. 9.0 months, P = .021), but overall response rate (ORR) was the same (75.0% vs. 81.0%, P = .76). There was no difference in PFS on TKI rechallenge (4.0 vs. 3.0 months, P = .94), although there was a trend toward higher ORR in T790M+ patients (22.2% vs. 0%, P = .12). T790M+ patients had a longer PFS on initial chemotherapy treatment (5.0 vs. 4.0 months, P = .025) and a trend toward higher ORR (40.0% vs. 21.4%, P = .31). CONCLUSION: Our study confirms that tumors expressing T790M have a more indolent progression of disease compared with their T790M- counterparts when treated with both first-line TKI and cytotoxic chemotherapy. Published by Elsevier Inc.
BACKGROUND: The secondary T790M mutation accounts for more than 50% of acquired tyrosine kinase inhibitor (TKI) resistance in patients with EGFR-mutated non-small-cell lung cancer (NSCLC). Recent reports suggest this resistance mutation may be more common among patients with longer progression-free survival (PFS) on first-line TKI therapy, but much is still unknown. MATERIALS AND METHODS: Our group collected medical records from patients who underwent a biopsy for T790M mutation testing while screening for clinical trials involving the drug rociletinib (CO-1686), a T790M mutation-specific TKI. Medical records were retrospectively analyzed for demographic data, PFS, and best response to previous therapies. RESULTS: Our patient cohort included 69 T790M+ patients and 28 T790M- patients. Patients who later developed a T790M mutation had a longer PFS on first-line TKI therapy (12.0 vs. 9.0 months, P = .021), but overall response rate (ORR) was the same (75.0% vs. 81.0%, P = .76). There was no difference in PFS on TKI rechallenge (4.0 vs. 3.0 months, P = .94), although there was a trend toward higher ORR in T790M+ patients (22.2% vs. 0%, P = .12). T790M+ patients had a longer PFS on initial chemotherapy treatment (5.0 vs. 4.0 months, P = .025) and a trend toward higher ORR (40.0% vs. 21.4%, P = .31). CONCLUSION: Our study confirms that tumors expressing T790M have a more indolent progression of disease compared with their T790M- counterparts when treated with both first-line TKI and cytotoxic chemotherapy. Published by Elsevier Inc.
Authors: David M Jackman; Beow Y Yeap; Lecia V Sequist; Neal Lindeman; Alison J Holmes; Victoria A Joshi; Daphne W Bell; Mark S Huberman; Balazs Halmos; Michael S Rabin; Daniel A Haber; Thomas J Lynch; Matthew Meyerson; Bruce E Johnson; Pasi A Jänne Journal: Clin Cancer Res Date: 2006-07-01 Impact factor: 12.531
Authors: J L Kuiper; D A M Heideman; E Thunnissen; M A Paul; A W van Wijk; P E Postmus; E F Smit Journal: Lung Cancer Date: 2014-03-23 Impact factor: 5.705
Authors: Rafael Rosell; Miguel Angel Molina; Carlota Costa; Sara Simonetti; Ana Gimenez-Capitan; Jordi Bertran-Alamillo; Clara Mayo; Teresa Moran; Pedro Mendez; Felipe Cardenal; Dolores Isla; Mariano Provencio; Manuel Cobo; Amelia Insa; Rosario Garcia-Campelo; Noemi Reguart; Margarita Majem; Santiago Viteri; Enric Carcereny; Ruth Porta; Bartomeu Massuti; Cristina Queralt; Itziar de Aguirre; Jose Miguel Sanchez; Maria Sanchez-Ronco; Jose Luis Mate; Aurelio Ariza; Susana Benlloch; Jose Javier Sanchez; Trever G Bivona; Charles L Sawyers; Miquel Taron Journal: Clin Cancer Res Date: 2011-01-13 Impact factor: 12.531
Authors: Jamie E Chaft; Geoffrey R Oxnard; Camelia S Sima; Mark G Kris; Vincent A Miller; Gregory J Riely Journal: Clin Cancer Res Date: 2011-08-19 Impact factor: 12.531
Authors: Pasi A Jänne; Xiaofei Wang; Mark A Socinski; Jeffrey Crawford; Thomas E Stinchcombe; Lin Gu; Marzia Capelletti; Martin J Edelman; Miguel A Villalona-Calero; Robert Kratzke; Everett E Vokes; Vincent A Miller Journal: J Clin Oncol Date: 2012-04-30 Impact factor: 44.544