Pascale Tomasini1, Celine Mascaux2, Kevin Jao3, Catherine Labbe3, Suzanne Kamel-Reid4, Tracy Stockley4, David M Hwang4, Natasha B Leighl3, Geoffrey Liu3, Penelope A Bradbury3, Melania Pintilie5, Ming-Sound Tsao4, Frances A Shepherd3. 1. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network and Department of Medicine, University of Toronto, Toronto, ON, Canada; Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France. Electronic address: pascale.tomasini@ap-hm.fr. 2. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network and Department of Medicine, University of Toronto, Toronto, ON, Canada; Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France. 3. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network and Department of Medicine, University of Toronto, Toronto, ON, Canada. 4. Department of Pathology, University Health Network and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. 5. Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, ON, Canada.
Abstract
BACKGROUND: KRAS and TP53 are common mutations in non-small-cell lung cancer (NSCLC). The Lung Adjuvant Cisplatin Evaluation Biological Program group found adjuvant chemotherapy to be deleterious in patients with coexisting KRAS/TP53 mutations. PATIENTS AND METHODS: To validate these results, patients with NSCLC tested for KRAS and TP53 mutations and receiving chemotherapy for any stage NSCLC were selected. Mutation status was analyzed using next generation sequencing (Illumina) or multiplex recurrent mutation detection (MassARRAY, Agena Biosciences) assays, and was correlated with clinical and demographic data. Disease-free (DFS) or progression-free survival (PFS) was the main endpoint, and overall survival (OS) was the secondary endpoint. RESULTS: Among 218 patients, 28 had coexisting KRAS/TP53 mutations, 77 TP53, 37 KRAS, 76 had neither KRAS nor TP53 mutation (WT/WT). There was no DFS/PFS difference for the KRAS/TP53 group versus all others among 99 patients who received adjuvant chemotherapy (hazard ratio [HR], 1.22; 95% confidence interval [CI], 0.61-2.44; P = .57), 27 stage III patients who received chemo-radiation (HR, 0.87; 95% CI, 0.32-2.38; P = .8), and 63 patients who received palliative chemotherapy (HR, 0.68; 95% CI, 0.31-1.48; P = .33). OS was longer in the WT/WT group compared with any other group (KRAS: HR, 1.87; 95% CI, 1.02-3.43; P = .043; TP53: HR, 2.17; 95% CI, 1.3-3.61; P = .0028; KRAS/TP53: HR, 2.06; 95% CI, 1.09-3.88; P = .026). No OS difference was seen for KRAS/TP53 compared with the other groups (HR, 1.26; 95% CI, 0.75-2.13; P = .38). CONCLUSIONS: There was no significant difference in DFS/PFS between the 4 groups. However, OS was longer for patients with TP53 and KRAS wild-type NSCLC who received chemotherapy for any stage compared with patients with KRAS, TP53 mutation, or double mutant tumors.
BACKGROUND:KRAS and TP53 are common mutations in non-small-cell lung cancer (NSCLC). The Lung Adjuvant Cisplatin Evaluation Biological Program group found adjuvant chemotherapy to be deleterious in patients with coexisting KRAS/TP53 mutations. PATIENTS AND METHODS: To validate these results, patients with NSCLC tested for KRAS and TP53 mutations and receiving chemotherapy for any stage NSCLC were selected. Mutation status was analyzed using next generation sequencing (Illumina) or multiplex recurrent mutation detection (MassARRAY, Agena Biosciences) assays, and was correlated with clinical and demographic data. Disease-free (DFS) or progression-free survival (PFS) was the main endpoint, and overall survival (OS) was the secondary endpoint. RESULTS: Among 218 patients, 28 had coexisting KRAS/TP53 mutations, 77 TP53, 37 KRAS, 76 had neither KRAS nor TP53 mutation (WT/WT). There was no DFS/PFS difference for the KRAS/TP53 group versus all others among 99 patients who received adjuvant chemotherapy (hazard ratio [HR], 1.22; 95% confidence interval [CI], 0.61-2.44; P = .57), 27 stage III patients who received chemo-radiation (HR, 0.87; 95% CI, 0.32-2.38; P = .8), and 63 patients who received palliative chemotherapy (HR, 0.68; 95% CI, 0.31-1.48; P = .33). OS was longer in the WT/WT group compared with any other group (KRAS: HR, 1.87; 95% CI, 1.02-3.43; P = .043; TP53: HR, 2.17; 95% CI, 1.3-3.61; P = .0028; KRAS/TP53: HR, 2.06; 95% CI, 1.09-3.88; P = .026). No OS difference was seen for KRAS/TP53 compared with the other groups (HR, 1.26; 95% CI, 0.75-2.13; P = .38). CONCLUSIONS: There was no significant difference in DFS/PFS between the 4 groups. However, OS was longer for patients with TP53 and KRAS wild-type NSCLC who received chemotherapy for any stage compared with patients with KRAS, TP53 mutation, or double mutant tumors.
Authors: Marcelo V Negrao; Ferdinandos Skoulidis; Meagan Montesion; Katja Schulze; Ilze Bara; Vincent Shen; Hao Xu; Sylvia Hu; Dawen Sui; Yasir Y Elamin; Xiuning Le; Michael E Goldberg; Karthikeyan Murugesan; Chang-Jiun Wu; Jianhua Zhang; David S Barreto; Jacqulyne P Robichaux; Alexandre Reuben; Tina Cascone; Carl M Gay; Kyle G Mitchell; Lingzhi Hong; Waree Rinsurongkawong; Jack A Roth; Stephen G Swisher; Jack Lee; Anne Tsao; Vassiliki Papadimitrakopoulou; Don L Gibbons; Bonnie S Glisson; Gaurav Singal; Vincent A Miller; Brian Alexander; Garrett Frampton; Lee A Albacker; David Shames; Jianjun Zhang; John V Heymach Journal: J Immunother Cancer Date: 2021-08 Impact factor: 13.751
Authors: Rodolfo L Chavez-Dominguez; Mario A Perez-Medina; Jose S Lopez-Gonzalez; Miriam Galicia-Velasco; Margarita Matias-Florentino; Santiago Avila-Rios; Uriel Rumbo-Nava; Alfonso Salgado-Aguayo; Claudia Gonzalez-Gonzalez; Dolores Aguilar-Cazares Journal: Front Oncol Date: 2021-12-13 Impact factor: 6.244