A Ono1, H Kenmotsu2, M Watanabe3, M Serizawa3, K Mori4, H Imai2, T Taira2, T Naito2, H Murakami2, T Nakajima5, Y Ohde6, M Endo7, N Yamamoto8, Y Koh3, T Takahashi2. 1. Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan a.ono@scchr.jp. 2. Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan. 3. Division of Drug Discovery and Development, Shizuoka Cancer Center Research Institute, Shizuoka, Japan. 4. Clinical Trial Coordination Office, Shizuoka Cancer Center, Shizuoka, Japan. 5. Division of Diagnostic Pathology, Shizuoka Cancer Center, Shizuoka, Japan. 6. Division of Thoracic Surgery, Shizuoka Cancer Center, Shizuoka, Japan. 7. Division of Diagnostic Radiology, Shizuoka Cancer Center, Shizuoka, Japan. 8. Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.
Abstract
BACKGROUND: Whether the mutant allele frequency (MAF) may also have predictive implications for tyrosine kinase inhibitor (TKI) therapy in patients with advanced epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma (AELAd) remains unknown. PATIENTS AND METHODS: Based on a biobanking system in conjunction with our institution, we assessed EGFR mutation status using pyrosequencing (Py) and by outsourcing laboratory tests, such as the Cycleave (Cy) and the Scorpion ARMS (A). RESULTS: Out of 705 patients enrolled in the Shizuoka Lung Cancer Mutation Study between July 2011 and March 2013, 102 AELAd patients were identified as carrying the L858R mutation (L858Rm) using Py to analyze histological specimens. Of these 102 patients, the EGFR mutation status was assessed using both Py and Cy in 48 patients: the median MAF of L858R (MAFLR) was 18.5% (range: 8%-82%), and 45 patients (94%) were identified as having an L858Rm using both Py and Cy. Three patients (6%) with discrepant L858Rm findings were only identified using Py. The plotting of a receiver operating characteristic curve to identify the discordance in L858Rm findings showed that the area under the curve for MAFLR was 0.967 (95% confidence interval: 0.91-1) and that an MAFLR of 9% resulted in high sensitivity (100%) and specificity (99%). Also, 29 patients with AELAd, excluding those with postoperative recurrences, had their L858R status assessed using Cy or A. The median age, 69 years (range: 47-84 years); male/female, 14 (48%)/15 (52%); smokers/never-smokers 13 (45%)/16 (55%); ECOG PS 0-1/2-3, 26 (90%)/3 (10%); stage IIIB/IV, 4 (14%)/25 (86%); median MAFLR, 18% (range: 8%-63%). Patients with an MAFLR of ≤9% had a significantly shorter progression-free survival (PFS) period after TKI therapy than those with an MAFLR of >9% (mPFS: 92 versus 284 days, P = 0.0027). CONCLUSION: The MAF may be a potential predictive factor of TKI treatment efficacy in patients with AELAd carrying the L858Rm.
BACKGROUND: Whether the mutant allele frequency (MAF) may also have predictive implications for tyrosine kinase inhibitor (TKI) therapy in patients with advanced epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma (AELAd) remains unknown. PATIENTS AND METHODS: Based on a biobanking system in conjunction with our institution, we assessed EGFR mutation status using pyrosequencing (Py) and by outsourcing laboratory tests, such as the Cycleave (Cy) and the Scorpion ARMS (A). RESULTS: Out of 705 patients enrolled in the Shizuoka Lung Cancer Mutation Study between July 2011 and March 2013, 102 AELAd patients were identified as carrying the L858R mutation (L858Rm) using Py to analyze histological specimens. Of these 102 patients, the EGFR mutation status was assessed using both Py and Cy in 48 patients: the median MAF of L858R (MAFLR) was 18.5% (range: 8%-82%), and 45 patients (94%) were identified as having an L858Rm using both Py and Cy. Three patients (6%) with discrepant L858Rm findings were only identified using Py. The plotting of a receiver operating characteristic curve to identify the discordance in L858Rm findings showed that the area under the curve for MAFLR was 0.967 (95% confidence interval: 0.91-1) and that an MAFLR of 9% resulted in high sensitivity (100%) and specificity (99%). Also, 29 patients with AELAd, excluding those with postoperative recurrences, had their L858R status assessed using Cy or A. The median age, 69 years (range: 47-84 years); male/female, 14 (48%)/15 (52%); smokers/never-smokers 13 (45%)/16 (55%); ECOG PS 0-1/2-3, 26 (90%)/3 (10%); stage IIIB/IV, 4 (14%)/25 (86%); median MAFLR, 18% (range: 8%-63%). Patients with an MAFLR of ≤9% had a significantly shorter progression-free survival (PFS) period after TKI therapy than those with an MAFLR of >9% (mPFS: 92 versus 284 days, P = 0.0027). CONCLUSION: The MAF may be a potential predictive factor of TKI treatment efficacy in patients with AELAd carrying the L858Rm.
Authors: Hersh A Ham-Karim; Henry Okuchukwu Ebili; Kirsty Manger; Wakkas Fadhil; Narmeen S Ahmad; Susan D Richman; Mohammad Ilyas Journal: Mol Diagn Ther Date: 2019-06 Impact factor: 4.074
Authors: Victor Rodriguez-Freixinos; Fiorella Ruiz-Pace; Lorena Fariñas-Madrid; Ana Christina Garrido-Castro; Guillermo Villacampa; Paolo Nuciforo; Ana Vivancos; Rodrigo Dienstmann; Ana Oaknin Journal: ESMO Open Date: 2019-03-08