Prior EGFR tyrosine-kinase inhibitor therapy did not influence the efficacy of subsequent pemetrexed plus platinum in advanced chemonaïve patients with EGFR-mutant lung adenocarcinoma

Background Tumor cells before and after epidermal growth-factor receptor (EGFR) tyrosine-kinase inhibitor (TKI) therapy might display different characteristics. The aim of this study was to evaluate the influence of prior EGFR TKI therapy on the efficacy of subsequent pemetrexed plus platinum (PP) in advanced chemonaïve patients with EGFR-mutant lung adenocarcinoma. Materials and methods Advanced chemonaïve patients with EGFR-mutant lung adenocarcinoma receiving PP as first-line chemotherapy were enrolled retrospectively in two medical centers of Taiwan. The objective of this study was to compare objective response rate (ORR), disease-control rates (DCR), progression-free survival (PFS), and overall survival (OS) of PP in patients with and without prior EGFR TKI therapy. Results In total, 105 patients were analyzed. Sixty-one patients (58.1%) had prior EGFR TKI therapy and used PP as second-line treatment. The other 44 patients (41.9%) received PP as first-line therapy. ORRs of PP in patients with and without prior EGFR TKI therapy were 24.6% and 38.6%, respectively (P=0.138). DCRs of the two groups were 62.3% and 65.9%, respectively (P=0.837). The median PFS (6.1 versus 6.1 months, P=0.639) and OS (34.4 versus 32.3 months, P=0.394) were comparable between the groups with and without prior EGFR TKI therapy. In a subgroup analysis of patients with prior EGFR TKI therapy, there was no significant association between the efficacy of first-line EGFR TKI and the outcome of subsequent PP therapy. Conclusion Our results suggested that prior EGFR TKI therapy would not influence the efficacy of subsequent PP therapy in advanced chemonaïve patients with EGFR-mutant lung adenocarcinoma.

[1]  Chun-Ming Tsai,et al.  Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  T. Mok,et al.  Treating patients with EGFR-sensitizing mutations: first line or second line--is there a difference? , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  T. Gauler,et al.  Significance of Folate Receptor Alpha and Thymidylate Synthase Protein Expression in Patients with Non–Small-Cell Lung Cancer Treated with Pemetrexed , 2013, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[4]  A. Moreira,et al.  Personalized medicine for non-small-cell lung cancer: implications of recent advances in tissue acquisition for molecular and histologic testing. , 2012, Clinical lung cancer.

[5]  Qinghua Zhou,et al.  Influence of chemotherapy on EGFR mutation status among patients with non-small-cell lung cancer. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  A. Rossi,et al.  First-line erlotinib followed by second-line cisplatin-gemcitabine chemotherapy in advanced non-small-cell lung cancer: the TORCH randomized trial. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  Hsuan-Yu Chen,et al.  Retrospective study of erlotinib in patients with advanced squamous lung cancer. , 2012, Lung cancer.

[8]  Young Hak Kim,et al.  Phase II study of carboplatin and pemetrexed in advanced non-squamous, non-small-cell lung cancer: Kyoto Thoracic Oncology Research Group Trial 0902 , 2012, Cancer Chemotherapy and Pharmacology.

[9]  T. Mok,et al.  Identification of Enriched Driver Gene Alterations in Subgroups of Non-Small Cell Lung Cancer Patients Based on Histology and Smoking Status , 2012, PloS one.

[10]  N. Leighl,et al.  Treatment paradigms for patients with metastatic non-small-cell lung cancer: first-, second-, and third-line. , 2012, Current oncology.

[11]  Jun Ma,et al.  Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. , 2011, The Lancet. Oncology.

[12]  M. Ladanyi,et al.  New Strategies in Overcoming Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Lung Cancer , 2011, Clinical Cancer Research.

[13]  Jih-Hsiang Lee,et al.  Good response to pemetrexed in patients of lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations. , 2011, Lung cancer.

[14]  J. Shih,et al.  Effectiveness of Tyrosine Kinase Inhibitors on “Uncommon” Epidermal Growth Factor Receptor Mutations of Unknown Clinical Significance in Non–Small Cell Lung Cancer , 2011, Clinical Cancer Research.

[15]  W. Franklin,et al.  Anaplastic Lymphoma Kinase Gene Rearrangements in Non-small Cell Lung Cancer are Associated with Prolonged Progression-Free Survival on Pemetrexed , 2011, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[16]  T. Chevalier,et al.  Should progression-free survival be the primary measure of efficacy for advanced NSCLC therapy? , 2010, Annals of oncology : official journal of the European Society for Medical Oncology.

[17]  A. Gemma,et al.  F1000 highlights , 2010 .

[18]  Y. Bang,et al.  The relationship between response to previous systemic treatment and the efficacy of subsequent pemetrexed therapy in advanced non-small cell lung cancer. , 2010, Lung cancer.

[19]  S. Toyooka,et al.  Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. , 2010, The Lancet. Oncology.

[20]  J. Abbruzzese,et al.  F1000 highlights , 2009, JAMA.

[21]  W. Travis,et al.  Histologic considerations for individualized systemic therapy approaches for the management of non-small cell lung cancer. , 2009, Chest.

[22]  Caicun Zhou,et al.  [Sensitivity of two cell lines with acquired resistance to gefitinib to several chemotherapeutic drugs]. , 2008, Zhonghua zhong liu za zhi [Chinese journal of oncology].

[23]  Johan Vansteenkiste,et al.  Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  J. Shih,et al.  Predictive Factors of Gefitinib Antitumor Activity in East Asian Advanced Non-small Cell Lung Cancer Patients , 2006, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[25]  J. Shih,et al.  Second‐line treatments after first‐line gefitinib therapy in advanced nonsmall cell lung cancer , 2010, International journal of cancer.

[26]  L. Schwartz,et al.  New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). , 2009, European journal of cancer.