TY - JOUR
T1 - Continuation of gefitinib plus chemotherapy prolongs progressionfree survival in advanced non-small cell lung cancer patients who get acquired resistance to gefitinib without T790M mutations
AU - Ding, Ting
AU - Zhou, Fei
AU - Chen, Xiaoxia
AU - Zhang, Shijia
AU - Liu, Yinan
AU - Sun, Hui
AU - Ren, Shengxiang
AU - Li, Xuefei
AU - Zhao, Chao
AU - Wang, Heyong
AU - Zhou, Caicun
N1 - Publisher Copyright:
© Journal of Thoracic Disease.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - Background: Aimed to identify the benefit population from continuation of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), this study investigated the efficacy of continuation of EGFR-TKIs plus chemotherapy beyond the response evaluation criteria in solid tumors-progressive disease (RECIST-PD) according to different progression modes and T790M mutational status. Methods: From November 2009 to July 2015, 630 patients with advanced non-small cell lung cancer (NSCLC) receiving gefitinib as initial EGFR-TKI treatment were screened in Shanghai Pulmonary Hospital. A total of 170 patients with documented gradual or dramatic progression after gefitinib treatment who received chemotherapy alone or in combination with gefitinib were included. Post-RECIST-PD progression-free survival (PPFS) between continuation of gefitinib plus chemotherapy and chemotherapy alone was assessed. Results: The incidence of T790M mutation was 42.9% (63/147) in patients who got acquired resistance in this study. Median PPFS was 4.0 months [95% confidence interval (CI), 3.1-4.9 months] in the chemotherapy group and 5.0 months (95% CI, 3.6-6.4 months) in the combination group with a borderline statistical significance (P=0.071). Continuation of gefitinib plus chemotherapy resulted in a significant improvement in PPFS compared with chemotherapy alone in patients with EGFRT790M-negative tumors [median PPFS: 6.6 vs. 3.5 months, hazard ratio (HR) 0.50, 95% CI, 0.29-0.88; P=0.011], especially in pemetrexed-based chemotherapy (HR 0.45, 95% CI, 0.24-0.86; P=0.011). PPFS was similar in patients with EGFRT790M-positive tumors (median PPFS: 5.0 vs. 5.5 months, HR 0.80, 95% CI, 0.40-1.61; P=0.520) or EGFRT790M-unknown tumors (median PPFS: 2.0 vs. 3.0 months, HR 1.40, 95% CI, 0.69-2.81; P=0.323). Conclusions: Our study showed that continuous gefitinib plus chemotherapy, especially pemetrexedbased therapy, significantly improved PPFS in patients with EGFRT790M-negative tumors as compared with chemotherapy alone, suggesting that this subtype of patients may derive clinical benefit from continuation of gefitinib treatment beyond progression.
AB - Background: Aimed to identify the benefit population from continuation of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), this study investigated the efficacy of continuation of EGFR-TKIs plus chemotherapy beyond the response evaluation criteria in solid tumors-progressive disease (RECIST-PD) according to different progression modes and T790M mutational status. Methods: From November 2009 to July 2015, 630 patients with advanced non-small cell lung cancer (NSCLC) receiving gefitinib as initial EGFR-TKI treatment were screened in Shanghai Pulmonary Hospital. A total of 170 patients with documented gradual or dramatic progression after gefitinib treatment who received chemotherapy alone or in combination with gefitinib were included. Post-RECIST-PD progression-free survival (PPFS) between continuation of gefitinib plus chemotherapy and chemotherapy alone was assessed. Results: The incidence of T790M mutation was 42.9% (63/147) in patients who got acquired resistance in this study. Median PPFS was 4.0 months [95% confidence interval (CI), 3.1-4.9 months] in the chemotherapy group and 5.0 months (95% CI, 3.6-6.4 months) in the combination group with a borderline statistical significance (P=0.071). Continuation of gefitinib plus chemotherapy resulted in a significant improvement in PPFS compared with chemotherapy alone in patients with EGFRT790M-negative tumors [median PPFS: 6.6 vs. 3.5 months, hazard ratio (HR) 0.50, 95% CI, 0.29-0.88; P=0.011], especially in pemetrexed-based chemotherapy (HR 0.45, 95% CI, 0.24-0.86; P=0.011). PPFS was similar in patients with EGFRT790M-positive tumors (median PPFS: 5.0 vs. 5.5 months, HR 0.80, 95% CI, 0.40-1.61; P=0.520) or EGFRT790M-unknown tumors (median PPFS: 2.0 vs. 3.0 months, HR 1.40, 95% CI, 0.69-2.81; P=0.323). Conclusions: Our study showed that continuous gefitinib plus chemotherapy, especially pemetrexedbased therapy, significantly improved PPFS in patients with EGFRT790M-negative tumors as compared with chemotherapy alone, suggesting that this subtype of patients may derive clinical benefit from continuation of gefitinib treatment beyond progression.
KW - Acquired resistance
KW - EGFR tyrosine kinase inhibitor (EGFR-TKI)
KW - Epidermal growth factor receptor (EGFR)
KW - Non-small-cell lung cancer (NSCLC)
KW - continuation
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U2 - 10.21037/jtd.2017.07.107
DO - 10.21037/jtd.2017.07.107
M3 - Article
AN - SCOPUS:85030085849
SN - 2072-1439
VL - 9
SP - 2923
EP - 2934
JO - Journal of Thoracic Disease
JF - Journal of Thoracic Disease
IS - 9
ER -