Randomized phase II trial of first-line treatment with pemetrexed-cisplatin, followed sequentially by gefitinib or pemetrexed, in East Asian, never-smoker patients with advanced non-small cell lung cancer

Myung Ju Ahn; James Chih Hsin Yang; Jun Liang; Jin Hyoung Kang; Qingyu Xiu; Yuh Min Chen; Julie Michelle Blair; Guangbin Peng; Carlos Linn; Mauro Orlando

doi:10.1016/j.lungcan.2012.03.011

Randomized phase II trial of first-line treatment with pemetrexed-cisplatin, followed sequentially by gefitinib or pemetrexed, in East Asian, never-smoker patients with advanced non-small cell lung cancer

Myung Ju Ahn
, James Chih Hsin Yang
, Jun Liang
, Jin Hyoung Kang
, Qingyu Xiu
, Yuh Min Chen
, Julie Michelle Blair
, Guangbin Peng
, Carlos Linn
, Mauro Orlando

Department of Internal Medicine

Sungkyunkwan University
National Taiwan University
Qingdao University
Changzheng Hospital
National Yang Ming Chiao Tung University
Eli Lilly

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

Introduction: Treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors or chemotherapy have shown improved survival outcomes in East Asian, never-smoker patients with non-small cell lung cancer (NSCLC). However, treatment sequence has not been optimized in patients with unknown EGFR mutation status. This trial compared first-line chemotherapy with pemetrexed (P)-cisplatin (C), followed by either gefitinib (G) or P maintenance. Methods: East Asian, never-smoker, chemo-naïve patients with stage IIIB/IV NSCLC, performance status ≤1 and unknown EGFR mutation status were randomized 1:1 to receive 4 cycles of pemetrexed [500mg/m ²]+cisplatin [75mg/m ²] q3 weeks, followed by maintenance with either gefitinib [250mg/d] (PC/G) or pemetrexed [500mg/m ²] q3 weeks and ≤2 optional cycles of cisplatin (PC/P). The primary endpoint, progression-free survival (PFS), was calculated from randomization date. Results: Between Feb and Nov 2007, 70 patients from China, Korea, and Taiwan were randomized and treated, among whom 59 patients (84.3%) had non-squamous NSCLC. Forty-nine patients (70.0%) completed the full sequential treatment (n= 25 G; n= 24 P). Median PFS was numerically longer for patients on PC/G (9.95 months) than those on PC/P (6.83. months; hazard ratio [HR] = 0.53, 95% confidence interval [CI] = 0.27, 1.04). In contrast, median overall survival was numerically higher for patients on PC/P (HR = 2.15, 95% CI = 0.83, 5.60), though there was a high censoring rate. Response rate was similar in both arms. Treatment arms were similar for grade 3/4/5 toxicities. Conclusions: East Asian never-smoker patients with advanced NSCLC and unknown EGFR mutation status had improved PFS following treatment with first-line PC and sequential G. Irrespective of subsequent maintenance treatment, induction PC was safe and efficacious, leading to prolonged OS in the Asian patient population.

Original language	English
Pages (from-to)	346-352
Number of pages	7
Journal	Lung Cancer
Volume	77
Issue number	2
DOIs	https://doi.org/10.1016/j.lungcan.2012.03.011
State	Published - Aug 2012

Bibliographical note

Funding Information:
M-JA, C-HY, JL, J-HK, QX, and Y-MC are clinical investigators for Study H3E-AA-S110 (Clinicaltrials.gov ID: NCT00409006 ). C-HY and Y-MC have received honoraria from Eli Lilly. J-H Kang received funding from Eli Lilly for study-related costs. GP, CL and MO are employees of JMB is a former employee of, and own stock in, Eli Lilly and Company. JL and QX have no relevant financial interests in this manuscript.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Gefitinib
Maintenance therapy
Never-smoker
Non-small cell lung cancer
Pemetrexed
Unknown EGFR mutation status

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Ahn, M. J., Yang, J. C. H., Liang, J., Kang, J. H., Xiu, Q., Chen, Y. M., Blair, J. M., Peng, G., Linn, C., & Orlando, M. (2012). Randomized phase II trial of first-line treatment with pemetrexed-cisplatin, followed sequentially by gefitinib or pemetrexed, in East Asian, never-smoker patients with advanced non-small cell lung cancer. Lung Cancer, 77(2), 346-352. https://doi.org/10.1016/j.lungcan.2012.03.011

@article{ca854c5217b84271819566c8088cc380,

title = "Randomized phase II trial of first-line treatment with pemetrexed-cisplatin, followed sequentially by gefitinib or pemetrexed, in East Asian, never-smoker patients with advanced non-small cell lung cancer",

abstract = "Introduction: Treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors or chemotherapy have shown improved survival outcomes in East Asian, never-smoker patients with non-small cell lung cancer (NSCLC). However, treatment sequence has not been optimized in patients with unknown EGFR mutation status. This trial compared first-line chemotherapy with pemetrexed (P)-cisplatin (C), followed by either gefitinib (G) or P maintenance. Methods: East Asian, never-smoker, chemo-na{\"i}ve patients with stage IIIB/IV NSCLC, performance status ≤1 and unknown EGFR mutation status were randomized 1:1 to receive 4 cycles of pemetrexed [500mg/m 2]+cisplatin [75mg/m 2] q3 weeks, followed by maintenance with either gefitinib [250mg/d] (PC/G) or pemetrexed [500mg/m 2] q3 weeks and ≤2 optional cycles of cisplatin (PC/P). The primary endpoint, progression-free survival (PFS), was calculated from randomization date. Results: Between Feb and Nov 2007, 70 patients from China, Korea, and Taiwan were randomized and treated, among whom 59 patients (84.3\%) had non-squamous NSCLC. Forty-nine patients (70.0\%) completed the full sequential treatment (n= 25 G; n= 24 P). Median PFS was numerically longer for patients on PC/G (9.95 months) than those on PC/P (6.83. months; hazard ratio [HR] = 0.53, 95\% confidence interval [CI] = 0.27, 1.04). In contrast, median overall survival was numerically higher for patients on PC/P (HR = 2.15, 95\% CI = 0.83, 5.60), though there was a high censoring rate. Response rate was similar in both arms. Treatment arms were similar for grade 3/4/5 toxicities. Conclusions: East Asian never-smoker patients with advanced NSCLC and unknown EGFR mutation status had improved PFS following treatment with first-line PC and sequential G. Irrespective of subsequent maintenance treatment, induction PC was safe and efficacious, leading to prolonged OS in the Asian patient population.",

keywords = "Gefitinib, Maintenance therapy, Never-smoker, Non-small cell lung cancer, Pemetrexed, Unknown EGFR mutation status",

author = "Ahn, \{Myung Ju\} and Yang, \{James Chih Hsin\} and Jun Liang and Kang, \{Jin Hyoung\} and Qingyu Xiu and Chen, \{Yuh Min\} and Blair, \{Julie Michelle\} and Guangbin Peng and Carlos Linn and Mauro Orlando",

note = "Funding Information: M-JA, C-HY, JL, J-HK, QX, and Y-MC are clinical investigators for Study H3E-AA-S110 (Clinicaltrials.gov ID: NCT00409006 ). C-HY and Y-MC have received honoraria from Eli Lilly. J-H Kang received funding from Eli Lilly for study-related costs. GP, CL and MO are employees of JMB is a former employee of, and own stock in, Eli Lilly and Company. JL and QX have no relevant financial interests in this manuscript. ",

year = "2012",

month = aug,

doi = "10.1016/j.lungcan.2012.03.011",

language = "English",

volume = "77",

pages = "346--352",

journal = "Lung Cancer",

issn = "0169-5002",

publisher = "Elsevier Ireland Ltd",

number = "2",

}

Ahn, MJ, Yang, JCH, Liang, J, Kang, JH, Xiu, Q, Chen, YM, Blair, JM, Peng, G, Linn, C & Orlando, M 2012, 'Randomized phase II trial of first-line treatment with pemetrexed-cisplatin, followed sequentially by gefitinib or pemetrexed, in East Asian, never-smoker patients with advanced non-small cell lung cancer', Lung Cancer, vol. 77, no. 2, pp. 346-352. https://doi.org/10.1016/j.lungcan.2012.03.011

Randomized phase II trial of first-line treatment with pemetrexed-cisplatin, followed sequentially by gefitinib or pemetrexed, in East Asian, never-smoker patients with advanced non-small cell lung cancer. / Ahn, Myung Ju; Yang, James Chih Hsin; Liang, Jun et al.
In: Lung Cancer, Vol. 77, No. 2, 08.2012, p. 346-352.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Randomized phase II trial of first-line treatment with pemetrexed-cisplatin, followed sequentially by gefitinib or pemetrexed, in East Asian, never-smoker patients with advanced non-small cell lung cancer

AU - Ahn, Myung Ju

AU - Yang, James Chih Hsin

AU - Liang, Jun

AU - Kang, Jin Hyoung

AU - Xiu, Qingyu

AU - Chen, Yuh Min

AU - Blair, Julie Michelle

AU - Peng, Guangbin

AU - Linn, Carlos

AU - Orlando, Mauro

N1 - Funding Information: M-JA, C-HY, JL, J-HK, QX, and Y-MC are clinical investigators for Study H3E-AA-S110 (Clinicaltrials.gov ID: NCT00409006 ). C-HY and Y-MC have received honoraria from Eli Lilly. J-H Kang received funding from Eli Lilly for study-related costs. GP, CL and MO are employees of JMB is a former employee of, and own stock in, Eli Lilly and Company. JL and QX have no relevant financial interests in this manuscript.

PY - 2012/8

Y1 - 2012/8

N2 - Introduction: Treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors or chemotherapy have shown improved survival outcomes in East Asian, never-smoker patients with non-small cell lung cancer (NSCLC). However, treatment sequence has not been optimized in patients with unknown EGFR mutation status. This trial compared first-line chemotherapy with pemetrexed (P)-cisplatin (C), followed by either gefitinib (G) or P maintenance. Methods: East Asian, never-smoker, chemo-naïve patients with stage IIIB/IV NSCLC, performance status ≤1 and unknown EGFR mutation status were randomized 1:1 to receive 4 cycles of pemetrexed [500mg/m 2]+cisplatin [75mg/m 2] q3 weeks, followed by maintenance with either gefitinib [250mg/d] (PC/G) or pemetrexed [500mg/m 2] q3 weeks and ≤2 optional cycles of cisplatin (PC/P). The primary endpoint, progression-free survival (PFS), was calculated from randomization date. Results: Between Feb and Nov 2007, 70 patients from China, Korea, and Taiwan were randomized and treated, among whom 59 patients (84.3%) had non-squamous NSCLC. Forty-nine patients (70.0%) completed the full sequential treatment (n= 25 G; n= 24 P). Median PFS was numerically longer for patients on PC/G (9.95 months) than those on PC/P (6.83. months; hazard ratio [HR] = 0.53, 95% confidence interval [CI] = 0.27, 1.04). In contrast, median overall survival was numerically higher for patients on PC/P (HR = 2.15, 95% CI = 0.83, 5.60), though there was a high censoring rate. Response rate was similar in both arms. Treatment arms were similar for grade 3/4/5 toxicities. Conclusions: East Asian never-smoker patients with advanced NSCLC and unknown EGFR mutation status had improved PFS following treatment with first-line PC and sequential G. Irrespective of subsequent maintenance treatment, induction PC was safe and efficacious, leading to prolonged OS in the Asian patient population.

AB - Introduction: Treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors or chemotherapy have shown improved survival outcomes in East Asian, never-smoker patients with non-small cell lung cancer (NSCLC). However, treatment sequence has not been optimized in patients with unknown EGFR mutation status. This trial compared first-line chemotherapy with pemetrexed (P)-cisplatin (C), followed by either gefitinib (G) or P maintenance. Methods: East Asian, never-smoker, chemo-naïve patients with stage IIIB/IV NSCLC, performance status ≤1 and unknown EGFR mutation status were randomized 1:1 to receive 4 cycles of pemetrexed [500mg/m 2]+cisplatin [75mg/m 2] q3 weeks, followed by maintenance with either gefitinib [250mg/d] (PC/G) or pemetrexed [500mg/m 2] q3 weeks and ≤2 optional cycles of cisplatin (PC/P). The primary endpoint, progression-free survival (PFS), was calculated from randomization date. Results: Between Feb and Nov 2007, 70 patients from China, Korea, and Taiwan were randomized and treated, among whom 59 patients (84.3%) had non-squamous NSCLC. Forty-nine patients (70.0%) completed the full sequential treatment (n= 25 G; n= 24 P). Median PFS was numerically longer for patients on PC/G (9.95 months) than those on PC/P (6.83. months; hazard ratio [HR] = 0.53, 95% confidence interval [CI] = 0.27, 1.04). In contrast, median overall survival was numerically higher for patients on PC/P (HR = 2.15, 95% CI = 0.83, 5.60), though there was a high censoring rate. Response rate was similar in both arms. Treatment arms were similar for grade 3/4/5 toxicities. Conclusions: East Asian never-smoker patients with advanced NSCLC and unknown EGFR mutation status had improved PFS following treatment with first-line PC and sequential G. Irrespective of subsequent maintenance treatment, induction PC was safe and efficacious, leading to prolonged OS in the Asian patient population.

KW - Gefitinib

KW - Maintenance therapy

KW - Never-smoker

KW - Non-small cell lung cancer

KW - Pemetrexed

KW - Unknown EGFR mutation status

UR - https://www.scopus.com/pages/publications/84863783193

U2 - 10.1016/j.lungcan.2012.03.011

DO - 10.1016/j.lungcan.2012.03.011

M3 - Article

C2 - 22534669

AN - SCOPUS:84863783193

SN - 0169-5002

VL - 77

SP - 346

EP - 352

JO - Lung Cancer

JF - Lung Cancer

IS - 2

ER -

Randomized phase II trial of first-line treatment with pemetrexed-cisplatin, followed sequentially by gefitinib or pemetrexed, in East Asian, never-smoker patients with advanced non-small cell lung cancer

Abstract

Bibliographical note

UN SDGs

Keywords

Access to Document

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