Journal of Shandong University (Health Sciences) ›› 2018, Vol. 56 ›› Issue (9): 29-34.doi: 10.6040/j.issn.1671-7554.0.2018.419

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Clinical analysis of gefitinib versus pemetrexed combined with cisplatin in patients with stage Ⅱ-ⅢA lung adenocarcinoma harbouring positive EGFR mutations

XIE Hounai, LI Meng, XU Lin, WANG Hui, PENG Yue, PENG Zhongmin   

  1. Department of Thoracic Surgery, Shandong Provincial Hospital Affliated to Shandong University, Jinan 250021, Shandong, China
  • Published:2022-09-27

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Abstract: Objective To compare the efficacy of geftinib versus pemetrexed/cisplatin in patients with EGFR-mutant stage Ⅱ-ⅢA lung adenocarcinoma, and to provide a reference for the therapy of postoperative lung adenocarcinoma. Methods A total of 103 patients with pathological stage Ⅱ-ⅢA lung adenocarcinoma combined with positive epidermal growth factor receptor(EGFR)mutations were enrolled between January 2013 and April 2017, and divided into pemetrexed + cisplatin(PC)group and gefitinib(GE)group. All events continued untill disease relapse, death, or unacceptable toxic effects. Factors affecting survival were assessed by Kaplan-Meier method and Cox regression analysis. 山 东 大 学 学 报 (医 学 版)56卷9期 -谢厚耐,等.吉非替尼对比培美曲塞联合顺铂治疗术后EGFR突变阳性Ⅱ~ⅢA期肺腺癌的临床分析 \=- Results The median follow-up time was 32.3 months in PC group and 37.0 months in GE group. Median disease-free survival(DFS)was significantly longer in GE group than that in PC group(34.9 vs 21.0 months, P=0.002). Overall survival(OS)was not significantly different between the two groups(P=0.182). The most common adverse events in PC group were neutropenia(58.8%)followed by nausea or vomiting(56.9%)and anemia(45.1%), and in GE group were rash(76.9%), aminotransferase elevation(48.1%)and diarrhoea(42.3%). The incidence of hematological toxicity, gastrointestinal toxicity and alopecia in PC group was significantly higher than that in GE group(P=0.001; P<0.001; P=0.020). Interstitial lung disease(ILD), which was regarded as the most severe treatment-related adverse event, was diagnosed in one patient after receiving gefitinib three months. The incidence of sever adverse events(grade≥3)was significantly lower in GE group than that in PC group(13.5% vs 33.3%, P=0.020). Conclusion Compared with chemotherapy with pemetrexed/cisplain, gefitinib shows a significant DFS benefit in patients with EGFR mutation-positive and completely resected stage Ⅱ-ⅢA lung adenocarcinoma and is associated with more favourable tolerability. Adjuvant geftinib could be a potential treatment option compared with adjuvant chemotherapy in these patients.

Key words: Lung adenocarcinoma, Epidermal growth factor receptor mutation, Gefitinib, Pemetrexed, Adjuvant chemotherapy

CLC Number: 

  • R655.3
[1] Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012 [J]. CA Cancer J Clin, 2015, 65(2): 87-108.
[2] Mountain CF. Revisions in the international system for staging lung cancer[J]. Chest, 1997, 111(6): 1710-1717.
[3] Eberhardt WE, De Ruysscher D, Weder W, et al. 2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer[J]. Ann Oncol, 2015, 26(8): 1573-1588.
[4] Kris MG, Gaspar LE, Chaft JE, et al. Adjuvant systemic therapy and adjuvant radiation therapy for stage Ⅰ to ⅢA completely resected non-small-cell lung cancers: American Society of Clinical Oncology/Cancer Care Ontario Clinical Practice Guideline update[J]. J Clin Oncol, 2017, 35(25): 2960-2974.
[5] Ettinger DS, Wood DE, Akerley W, et al. NCCN guidelines insights: non-small cell lung cancer, version 4.2016[J]. J Natl Compr Canc Netw, 2016, 14(3): 255-264.
[6] Zhi XY, Yu JM, Shi YK. Chinese guidelines on the diagnosis and treatment of primary lung cancer(2015 version)[J]. Cancer, 2016, 121(suppl 17): 3165-3181.
[7] Kreuter M, Vansteenkiste J, Fischer JR, et al. Three-year follow-up of a randomized phase II trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine(the TREAT study)[J]. J Thorac Oncol, 2016, 11(1): 85-93.
[8] Zhai X, Zheng Q, Yang L, et al. Impact of platinum/pemetrexed combination versus other platinum-based regimens on adjuvant chemotherapy in resected lung adenocarcinoma[J]. Sci Rep, 2017, 7(1): 1453. doi: 10.1038/s41598-017-01347-6.
[9] Ettinger DS, Wood DE, Aisner DL, et al. Non-small cell lung cancer, version 5.2017, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2017, 15(4): 504-535.
[10] Schmid-Bindert G, Engel-Riedel W, Reck M, et al. A randomized Phase 2 study of pemetrexed in combination with cisplatin or carboplatin as adjuvant chemotherapy in patients with completely resected stage ⅠB or Ⅱ Non-Small-Cell Lung Cancer[J]. Lung Cancer, 2015, 90(3): 397-404.
[11] Karapanagiotou EM, Boura PG, Papamichalis G, et al. Carboplatin-pemetrexed adjuvant chemotherapy in resected non-small cell lung cancer(NSCLC): a phase II study[J]. Anticancer Res, 2009, 29(10): 4297-4301.
[12] Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma[J]. N Engl J Med, 2009, 361(10): 947-957.
[13] Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR[J]. N Engl J Med, 2010, 362(25): 2380-2388.
[14] Mitsudomi T, Morita S, Yatabe Y, 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[J]. Lancet Oncol, 2010, 11(2): 121-128.
[15] Goss GD, OCallaghan C, Lorimer I, et al. Gefitinib versus placebo in completely resected non-small-cell lung cancer: results of the NCIC CTG BR19 study[J]. J Clin Oncol, 2013, 31(27): 3320-3326.
[16] Kelly K, Altorki NK, Eberhardt WE, et al. Adjuvant erlotinib versus placebo in patients with stage ⅠB-ⅢA non-small-cell lung cancer(RADIANT): a randomized, double-blind, phase Ⅲ trial[J]. J Clin Oncol, 2015, 33(34): 4007-4014.
[17] Lv C, An C, Feng Q, et al. A retrospective study of stage I to IIIa lung adenocarcinoma after resection: what is the optimal adjuvant modality for patients with an EGFR mutation?[J] Clin Lung Cancer, 2015, 16(6): e173-e181. doi: 10.1016/j.cllc.2015.04.002.
[18] Zhong WZ, Wang Q, Mao WM, et al. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage Ⅱ-ⅢA(N1-N2)EGFR-mutant NSCLC(ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study[J]. Lancet Oncol, 2017, 19(1): 139-148.
[19] Janjigian YY, Park BJ, Zakowski MF, et al. Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor EGFR mutations[J]. J Thorac Oncol, 2011, 6(3): 569-575.
[20] Takahashi K.[Lung cancer: progress in diagnosis and treatments. Topics: Ⅲ. Treatment; 3. Chemotherapy for patients with non-small cell lung cancer, 1)Cytotoxic drug treatment, maintenance therapy, and secondary line treatment] [J]. Nihon Naika Gakkai Zasshi, 2014, 103(6): 1306-1313.
[21] Kang CH, Ra YJ, Kim YT, et al. The impact of multiple metastatic nodal stations on survival in patients with resectable N1 and N2 nonsmall-cell lung cancer[J]. Ann Thorac Surg, 2008, 86(4): 1092-1097.
[22] Ding PN, Lord SJ, Gebski V, et al. Risk of treatment-related toxicities from EGFR tyrosine kinase inhibitors: a Meta-analysis of clinical trials of gefitinib, erlotinib, and afatinib in advanced EGFR-mutated non-small cell lung cancer[J]. J Thorac Oncol, 2017, 12(4): 633-643.
[23] Ando M, Okamoto I, Yamamoto N, et al. Predictive factors for interstitial lung disease, antitumor response, and survival in non-small-cell lung cancer patients treated with gefitinib[J]. J Clin Oncol, 2006, 24(16): 2549-2556.
[24] Kudoh S, Kato H, Nishiwaki Y, et al. Interstitial lung disease in Japanese patients with lung cancer: a cohort and nested case-control study[J]. Am J Respir Crit Care Med, 2008, 177(12): 1348-1357.
[25] Shi L, Tang J, Tong L, et al. Risk of interstitial lung disease with gefitinib and erlotinib in advanced non-small cell lung cancer: a systematic review and meta-analysis of clinical trials[J]. Lung Cancer, 2014, 83(2): 231-239.
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