• Catherine Labbé, Michael Cabanero, Grzegorz J Korpanty, Pascale Tomasini, Mark K Doherty, Céline Mascaux, Kevin Jao, Bethany Pitcher, Rick Wang, Melania Pintilie, Natasha B Leighl, Ronald Feld, Geoffrey Liu, Penelope Ann Bradbury, Suzanne Kamel-Reid, Ming-Sound Tsao, and Frances A Shepherd.
• Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, ON, M5G 2M9, Canada; Division of Respirology and Thoracic Surgery, Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Chemin Ste-Foy, Québec, QC, G1V 4G5, Canada. Electronic address: catherine.labbe@criucpq.ulaval.ca.
• Lung Cancer. 2017 Sep 1; 111: 23-29.

IntroductionTP53 mutations are common in non-small cell lung cancer (NSCLC) and have been reported as prognostic of poor outcome. The impact of TP53 co-mutations in epidermal growth factor receptor (EGFR)-mutated NSCLC is unclear.Materials And MethodsTissue from 105 patients with EGFR-mutated NSCLC at Princess Margaret Cancer Centre was analyzed by next-generation or Sanger sequencing to determine TP53 mutational status. Associations between TP53 status and baseline patient and tumor characteristics, treatments and outcomes (relapse-free survival [RFS] after surgical resection, overall survival [OS], overall response rate [ORR] and progression-free survival [PFS] on EGFR tyrosine kinase inhibitors [TKIs]), were investigated.ResultsDual TP53/EGFR mutations were found in 43/105 patients (41%). Among 76 patients who underwent surgical resection, neither RFS (HR 0.99, CI 0.56-1.75, p=0.96) nor OS (HR 1.39, CI 0.70-2.77; p=0.35) was associated with TP53 status. Sixty patients (24 TP53 MUT; 36 TP53 WT) received first-generation EGFR TKIs for advanced disease. ORR was not significantly different (TP53 MUT 54%, WT 66%, p=0.42). There was a non-significant trend towards shorter PFS on EGFR TKIs with TP53 mutation (HR 1.74, CI 0.98-3.10, p=0.06). When limited to TP53 missense mutations (n=17), PFS was significantly shorter (HR 1.91, CI 1.01-3.60, p=0.04). Among 11 evaluable patients treated with T790M inhibitors, ORR was not significantly different (TP53 MUT 3/3 [100%], WT 7/8 [88%]).ConclusionsPatients with dual TP53/EGFR mutations, especially missense mutations, had marginally lower response rates and shorter PFS when treated with EGFR TKI therapy. Larger datasets are required to validate these observations.Copyright © 2017 Elsevier B.V. All rights reserved.

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