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Erschienen in: Annals of Surgical Oncology 6/2014

01.06.2014 | Thoracic Oncology

Pemetrexed-Carboplatin Adjuvant Chemotherapy With or Without Gefitinib in Resected Stage IIIA-N2 Non-Small Cell Lung Cancer Harbouring EGFR Mutations: A Randomized, Phase II Study

verfasst von: Ning Li, MD, Wei Ou, MD, Xiong Ye, MD, Hai-Bo Sun, MD, Liang Zhang, MD, Qin Fang, MD, Song-Liang Zhang, MD, Bao-Xiao Wang, Si-Yu Wang, MD

Erschienen in: Annals of Surgical Oncology | Ausgabe 6/2014

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Abstract

Background

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) show great efficacy in patients with advanced non-small cell lung cancer (NSCLC) with EGFR mutations. The efficacy and safety of gefitinib following adjuvant chemotherapy in patients with EGFR mutation are unknown.

Methods

In this open-label, phase II study, patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations (either exon 19 deletion or L858R point mutation) were assigned randomly to receive pemetrexed (500 mg/m2) and carboplatin (AUC = 5), administered every 21 days for 4 cycles, followed with or without gefitinib (250 mg/day) for 6 months. The primary end point was disease-free survival (DFS).

Results

From August 2008 to September 2011, 60 patients were included in our center. DFS was significantly longer among those who received pemetrexed and carboplatin (PC)-gefitinib than among those who received PC alone [hazard ratio (HR), 0.37; 95 % confidence interval (CI) 0.16–0.85; P = 0.014; median, 39.8 vs. 27.0 months]. The rates of 2-year DFS were 78.9 % in the PC-gefitinib group and 54.2 % in the PC alone group. The rates of 2-year overall survival (OS) were 92.4 % in the PC-gefitinib group and 77.4 % in the PC alone group (HR, 0.37; 95 % CI 0.12–1.11, P = 0.076). The most common adverse event was rash (43.3 %, 13/30) in the PC-gefitinib group and the administration of gefitinib following chemotherapy was well tolerated.

Conclusions

The administration of gefitinib following PC adjuvant therapy shows significant improvement in DFS in patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations.
Literatur
1.
Zurück zum Zitat Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.PubMedCrossRef Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.PubMedCrossRef
2.
Zurück zum Zitat Mountain CF. Revisions in the international system for staging lung cancer. Chest. 1997;111(6):1710–7.PubMedCrossRef Mountain CF. Revisions in the international system for staging lung cancer. Chest. 1997;111(6):1710–7.PubMedCrossRef
3.
Zurück zum Zitat Scagliotti GV, Fossati R, Torri V, et al. Randomized study of adjuvant chemotherapy for completely resected stage I, II, or IIIA non-small-cell lung cancer. J Natl Cancer Inst. 2003;95(19):1453–61.PubMedCrossRef Scagliotti GV, Fossati R, Torri V, et al. Randomized study of adjuvant chemotherapy for completely resected stage I, II, or IIIA non-small-cell lung cancer. J Natl Cancer Inst. 2003;95(19):1453–61.PubMedCrossRef
4.
Zurück zum Zitat Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004;350(4):351–60.PubMedCrossRef Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004;350(4):351–60.PubMedCrossRef
5.
Zurück zum Zitat Waller D, Peake MD, Stephens RJ, et al. Chemotherapy for patients with non-small cell lung cancer: the surgical setting of the Big Lung Trial. Eur J Cardiothorac Surg. 2004;26(1):173–82.PubMedCrossRef Waller D, Peake MD, Stephens RJ, et al. Chemotherapy for patients with non-small cell lung cancer: the surgical setting of the Big Lung Trial. Eur J Cardiothorac Surg. 2004;26(1):173–82.PubMedCrossRef
6.
Zurück zum Zitat Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med. 2005;352(25):2589–97.PubMedCrossRef Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med. 2005;352(25):2589–97.PubMedCrossRef
7.
Zurück zum Zitat Douillard JY, Rosell R, De Lena M, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol. 2006;7(9):719–27.PubMedCrossRef Douillard JY, Rosell R, De Lena M, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol. 2006;7(9):719–27.PubMedCrossRef
8.
Zurück zum Zitat Pignon JP, Tribodet H, Scagliotti GV, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26(21):3552–9.PubMedCrossRef Pignon JP, Tribodet H, Scagliotti GV, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26(21):3552–9.PubMedCrossRef
9.
Zurück zum Zitat Hanna N, Shepherd FA, Fossella FV, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004;22(9):1589–97.PubMedCrossRef Hanna N, Shepherd FA, Fossella FV, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004;22(9):1589–97.PubMedCrossRef
10.
Zurück zum Zitat Scagliotti GV, Parikh P, von Pawel J, 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. J Clin Oncol. 2008;26(21):3543–51.PubMedCrossRef Scagliotti GV, Parikh P, von Pawel J, 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. J Clin Oncol. 2008;26(21):3543–51.PubMedCrossRef
11.
Zurück zum Zitat Gronberg BH, Bremnes RM, Flotten O, et al. Phase III study by the Norwegian lung cancer study group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2009;27(19):3217–24.PubMedCrossRef Gronberg BH, Bremnes RM, Flotten O, et al. Phase III study by the Norwegian lung cancer study group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2009;27(19):3217–24.PubMedCrossRef
12.
Zurück zum Zitat Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947–57.PubMedCrossRef Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947–57.PubMedCrossRef
13.
Zurück zum Zitat 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. Lancet Oncol. 2010;11(2):121–8.PubMedCrossRef 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. Lancet Oncol. 2010;11(2):121–8.PubMedCrossRef
14.
Zurück zum Zitat Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362(25):2380–8.PubMedCrossRef Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362(25):2380–8.PubMedCrossRef
15.
Zurück zum Zitat Giaccone G, Herbst RS, Manegold C, et al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial–INTACT 1. J Clin Oncol. 2004;22(5):777–84.PubMedCrossRef Giaccone G, Herbst RS, Manegold C, et al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial–INTACT 1. J Clin Oncol. 2004;22(5):777–84.PubMedCrossRef
16.
Zurück zum Zitat Herbst RS, Giaccone G, Schiller JH, et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial–INTACT 2. J Clin Oncol. 2004;22(5):785–94.PubMedCrossRef Herbst RS, Giaccone G, Schiller JH, et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial–INTACT 2. J Clin Oncol. 2004;22(5):785–94.PubMedCrossRef
17.
Zurück zum Zitat Herbst RS, Prager D, Hermann R, et al. TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2005;23(25):5892–9.PubMedCrossRef Herbst RS, Prager D, Hermann R, et al. TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2005;23(25):5892–9.PubMedCrossRef
18.
Zurück zum Zitat Gatzemeier U, Pluzanska A, Szczesna A, et al. Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial. J Clin Oncol. 2007;25(12):1545–52.PubMedCrossRef Gatzemeier U, Pluzanska A, Szczesna A, et al. Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial. J Clin Oncol. 2007;25(12):1545–52.PubMedCrossRef
19.
Zurück zum Zitat Zhou C, Wu YL, Chen G, 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. Lancet Oncol. 2011;12(8):735–42.PubMedCrossRef Zhou C, Wu YL, Chen G, 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. Lancet Oncol. 2011;12(8):735–42.PubMedCrossRef
20.
Zurück zum Zitat Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239–46.PubMedCrossRef Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239–46.PubMedCrossRef
21.
Zurück zum Zitat 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 Clin Oncol. 2013;31:3320–6.PubMedCrossRef 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 Clin Oncol. 2013;31:3320–6.PubMedCrossRef
22.
Zurück zum Zitat Sun HB, Zheng Y, Ou W, et al. Association between hormone receptor expression and epidermal growth factor receptor mutation in patients operated on for non-small cell lung cancer. Ann Thorac Surg. 2011;91(5):1562–7.PubMedCrossRef Sun HB, Zheng Y, Ou W, et al. Association between hormone receptor expression and epidermal growth factor receptor mutation in patients operated on for non-small cell lung cancer. Ann Thorac Surg. 2011;91(5):1562–7.PubMedCrossRef
23.
Zurück zum Zitat Sun HB, Ou W, Li Y, et al. Epidermal growth factor receptor mutation status and adjuvant chemotherapy in resected advanced non-small-cell lung cancer. Clin Lung Cancer. 2013;14(4):376–382.PubMedCrossRef Sun HB, Ou W, Li Y, et al. Epidermal growth factor receptor mutation status and adjuvant chemotherapy in resected advanced non-small-cell lung cancer. Clin Lung Cancer. 2013;14(4):376–382.PubMedCrossRef
24.
Zurück zum Zitat 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 Thorac Oncol. 2011;6(3):569–75.PubMedCentralPubMedCrossRef 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 Thorac Oncol. 2011;6(3):569–75.PubMedCentralPubMedCrossRef
25.
Zurück zum Zitat Neal JW, Pennell NA, Govindan R, Launuti M, Pam R, Rosovsky G. The SELECT study: A multicenter phase II trial of adjuvant erlotinib in resected epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). J Clin Oncol. 2012;30(Suppl; abstr 7010). Neal JW, Pennell NA, Govindan R, Launuti M, Pam R, Rosovsky G. The SELECT study: A multicenter phase II trial of adjuvant erlotinib in resected epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). J Clin Oncol. 2012;30(Suppl; abstr 7010).
26.
Zurück zum Zitat Ou W, Sun HB, Ye X, et al. Adjuvant carboplatin-based chemotherapy in resected stage IIIA-N2 non-small cell lung cancer. J Thorac Oncol. 2010;5(7):1033–41.PubMed Ou W, Sun HB, Ye X, et al. Adjuvant carboplatin-based chemotherapy in resected stage IIIA-N2 non-small cell lung cancer. J Thorac Oncol. 2010;5(7):1033–41.PubMed
27.
Zurück zum Zitat Wang SY, Ye X, Ou W, Lin YB, Zhang BB, Yang H. Risk of cerebral metastases for postoperative locally advanced non-small-cell lung cancer. Lung Cancer. 2009;64(2):238–43.PubMedCrossRef Wang SY, Ye X, Ou W, Lin YB, Zhang BB, Yang H. Risk of cerebral metastases for postoperative locally advanced non-small-cell lung cancer. Lung Cancer. 2009;64(2):238–43.PubMedCrossRef
Metadaten
Titel
Pemetrexed-Carboplatin Adjuvant Chemotherapy With or Without Gefitinib in Resected Stage IIIA-N2 Non-Small Cell Lung Cancer Harbouring EGFR Mutations: A Randomized, Phase II Study
verfasst von
Ning Li, MD
Wei Ou, MD
Xiong Ye, MD
Hai-Bo Sun, MD
Liang Zhang, MD
Qin Fang, MD
Song-Liang Zhang, MD
Bao-Xiao Wang
Si-Yu Wang, MD
Publikationsdatum
01.06.2014
Verlag
Springer US
Erschienen in
Annals of Surgical Oncology / Ausgabe 6/2014
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-014-3586-9

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