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

Ting Ding, Fei Zhou, Xiaoxia Chen, Shijia Zhang, Yinan Liu, Hui Sun, Shengxiang Ren, Xuefei Li, Chao Zhao, Heyong Wang, Caicun Zhou

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13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2923-2934
Number of pages12
JournalJournal of Thoracic Disease
Volume9
Issue number9
DOIs
StatePublished - Sep 1 2017

Bibliographical note

Publisher Copyright:
© Journal of Thoracic Disease.

Keywords

  • Acquired resistance
  • EGFR tyrosine kinase inhibitor (EGFR-TKI)
  • Epidermal growth factor receptor (EGFR)
  • Non-small-cell lung cancer (NSCLC)
  • continuation

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