Continuation of gefitinib plus chemotherapy prolongs progression-free 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

doi:10.21037/jtd.2017.07.107

Continuation of gefitinib plus chemotherapy prolongs progression-free survival in advanced non-small cell lung cancer patients who get acquired resistance to gefitinib without T790M mutations

J Thorac Dis. 2017 Sep;9(9):2923-2934. doi: 10.21037/jtd.2017.07.107.

Authors

Ting Ding^{1

2}, Fei Zhou¹, Xiaoxia Chen¹, Shijia Zhang¹, Yinan Liu¹, Hui Sun¹, Shengxiang Ren¹, Xuefei Li³, Chao Zhao³, Heyong Wang⁴, Caicun Zhou¹

Affiliations

¹ Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
² Department of Medical Oncology, Medical college of Soochow University, Suzhou 215123, China.
³ Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
⁴ The Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.

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 EGFR^T790M-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 EGFR^T790M-positive tumors (median PPFS: 5.0 vs. 5.5 months, HR 0.80, 95% CI, 0.40-1.61; P=0.520) or EGFR^T790M-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 pemetrexed-based therapy, significantly improved PPFS in patients with EGFR^T790M-negative tumors as compared with chemotherapy alone, suggesting that this subtype of patients may derive clinical benefit from continuation of gefitinib treatment beyond progression.

Keywords: EGFR tyrosine kinase inhibitor (EGFR-TKI); Non-small-cell lung cancer (NSCLC); acquired resistance; continuation; epidermal growth factor receptor (EGFR).