BACKGROUND: Molecular profiling of advanced EGFR mutated NSCLC has recently demonstrated the co-existence of multiple genetic alterations. Specifically, co-existing KRAS-mutations in EGFR NSCLCs have been described, despite their prevalence at progression and their role in the response to EGFR tyrosine kinase inhibitors (TKIs) remain marginally explored. Aim of our study was to investigate the prevalence of co-existing KRAS mutations at the time of progressive disease and explore their impact on clinical outcome. MATERIALS AND METHODS: We retrospectively analyzed by digital droplet PCR prevalence of KRAS co-mutations in 106 plasma samples of EGFR mutated NSCLC patients, in progressive disease after EGFR TKI treatment as first-line therapy. RESULTS: KRAS co-mutations (codon 12 and 13) were identified in 3 patients (2.8% of analyzed samples), with low allelic frequency (<0.2%), and had a negative impact on clinical outcome to first-line EGFR TKI. CONCLUSION: Detection of KRAS mutations in cell-free DNA of EGFR mutant NSCLC patients at progression after first or second generation EGFR TKI is a rare event. Due to their low abundance, the negative impact of KRAS mutations on the response to EGFR TKI remains to be confirmed in larger studies.
BACKGROUND: Molecular profiling of advanced EGFR mutated NSCLC has recently demonstrated the co-existence of multiple genetic alterations. Specifically, co-existing KRAS-mutations in EGFR NSCLCs have been described, despite their prevalence at progression and their role in the response to EGFR tyrosine kinase inhibitors (TKIs) remain marginally explored. Aim of our study was to investigate the prevalence of co-existing KRAS mutations at the time of progressive disease and explore their impact on clinical outcome. MATERIALS AND METHODS: We retrospectively analyzed by digital droplet PCR prevalence of KRAS co-mutations in 106 plasma samples of EGFR mutated NSCLC patients, in progressive disease after EGFR TKI treatment as first-line therapy. RESULTS: KRAS co-mutations (codon 12 and 13) were identified in 3 patients (2.8% of analyzed samples), with low allelic frequency (<0.2%), and had a negative impact on clinical outcome to first-line EGFR TKI. CONCLUSION: Detection of KRAS mutations in cell-free DNA of EGFR mutant NSCLC patients at progression after first or second generation EGFR TKI is a rare event. Due to their low abundance, the negative impact of KRAS mutations on the response to EGFR TKI remains to be confirmed in larger studies.
Authors: Eric Santoni-Rugiu; Linea C Melchior; Edyta M Urbanska; Jan N Jakobsen; Karin de Stricker; Morten Grauslund; Jens B Sørensen Journal: Cancers (Basel) Date: 2019-07-01 Impact factor: 6.639
Authors: Mariam Jamal-Hanjani; Gareth A Wilson; Nicholas McGranahan; Nicolai J Birkbak; Thomas B K Watkins; Selvaraju Veeriah; Seema Shafi; Diana H Johnson; Richard Mitter; Rachel Rosenthal; Max Salm; Stuart Horswell; Mickael Escudero; Nik Matthews; Andrew Rowan; Tim Chambers; David A Moore; Samra Turajlic; Hang Xu; Siow-Ming Lee; Martin D Forster; Tanya Ahmad; Crispin T Hiley; Christopher Abbosh; Mary Falzon; Elaine Borg; Teresa Marafioti; David Lawrence; Martin Hayward; Shyam Kolvekar; Nikolaos Panagiotopoulos; Sam M Janes; Ricky Thakrar; Asia Ahmed; Fiona Blackhall; Yvonne Summers; Rajesh Shah; Leena Joseph; Anne M Quinn; Phil A Crosbie; Babu Naidu; Gary Middleton; Gerald Langman; Simon Trotter; Marianne Nicolson; Hardy Remmen; Keith Kerr; Mahendran Chetty; Lesley Gomersall; Dean A Fennell; Apostolos Nakas; Sridhar Rathinam; Girija Anand; Sajid Khan; Peter Russell; Veni Ezhil; Babikir Ismail; Melanie Irvin-Sellers; Vineet Prakash; Jason F Lester; Malgorzata Kornaszewska; Richard Attanoos; Haydn Adams; Helen Davies; Stefan Dentro; Philippe Taniere; Brendan O'Sullivan; Helen L Lowe; John A Hartley; Natasha Iles; Harriet Bell; Yenting Ngai; Jacqui A Shaw; Javier Herrero; Zoltan Szallasi; Roland F Schwarz; Aengus Stewart; Sergio A Quezada; John Le Quesne; Peter Van Loo; Caroline Dive; Allan Hackshaw; Charles Swanton Journal: N Engl J Med Date: 2017-04-26 Impact factor: 91.245
Authors: S Li; L Li; Y Zhu; C Huang; Y Qin; H Liu; L Ren-Heidenreich; B Shi; H Ren; X Chu; J Kang; W Wang; J Xu; K Tang; H Yang; Y Zheng; J He; G Yu; N Liang Journal: Br J Cancer Date: 2014-04-17 Impact factor: 7.640