化疗后再使用EGFR-TKI治疗晚期非小细胞肺癌的临床研究

  目的  表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitor，EGFR-TKI)治疗晚期非小细胞肺癌(NSCLC)虽疗效显著，且安全性好，但最终都会发生耐药。EGFR-TKI耐药机制复杂，应对困难，本研究旨在探讨EGFR-TKI治疗晚期NSCLC获得性耐药的患者，化疗后再次应用EGFR-TKI的疗效。  方法  前瞻性对EGFR-TKI治疗晚期NSCLC长期获益后获得性耐药的27例患者，先化疗，后再次应用EGFR-TKI治疗，吉非替尼250 mg qd或厄洛替尼150 mg qd至疾病进展；依据RECIST标准评价疗效，比较再使用原EGFR-TKI与另一种EGFR-TKI的疗效。  结果  27例患者全为晚期肺腺癌，完全缓解(CR)为1例(3.7%)、部分缓解(PR)为8例(29.6%)、稳定(SD)为14例(51.9%)、进展(PD)为4例(14.8%)，有效率(RR)为33.3%，疾病控制率(DCR)为85.2% (95% CI为62~94)，mPFS为6个月。13例再用原EGFR-TKI (同药组) CR为1例(7.6%)，PR为2例(15.4%)、SD为8例(61.5%)，RR为23%，PD为2例(15.4%)，DCR为86.4%，其mPFS为5个月；14例再用另一种EGFR-TKI (换药组) CR为0例，PR为6例(42.8%)，SD为6例(42.8%)，进展为2例(14.3%)，RR为42.8%，其mPFS为9.5个月，DCR为85.7%，两组DCR比较无显著性差异(P>0.05)，两组的mPFS比较有显著性差异(P < 0.05)；mPFS换药组明显长于同药组。  结论  EGFR-TKI治疗晚期NSCLC长期获益后获得性耐药的患者，先化疗、后再次应用EGFR-TKI，大部分患者仍能取得一定疗效。 

Effect of EGFR-TKI retreatment following chemotherapy for advanced non-small cell lung cancer patients who underwent EGFR-TKI

  Objective  Non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-activating mutations have higher response rate and more prolonged survival following treatment with single-agent EGFR tyrosine kinase inhibitor (EGFR-TKI) compared with patients with wild-type EGFR. However, all patients treated with reversible inhibitors develop acquired resistance over time. The mechanisms of resistance are complicated. The lack of established therapeutic options for patients after a failed EGFR-TKI treatment poses a great challenge to physicians in managing this group of lung cancer patients. This study evaluates the influence of EGFR-TKI retreatment following chemotherapy after failure of initial EGFR-TKI within at least six months on NSCLC patients.  Methods  The data of 27 patients who experienced treatment failure from their initial use of EGFR-TKI within at least 6 months were analyzed. After chemotherapy, the patients were retreated with EGFR-TKI (gefitinib 250 mg qd or erlotinib 150 mg qd), and the tumor progression was observed. The patients were assessed for adverse events and response to therapy. Targeted tumor lesions were assessed with CT scan.  Results  Of the 27 patients who received EGFR–TKI retreatment, 1 (3.7%) patient was observed in complete response (CR), 8 (29.6%) patients in partial response (PR), 14 (51.9%) patients in stable disease (SD), and 4 (14.8%) patients in progressive disease (PD). The disease control rate (DCR) was 85.2% (95% CI = 62%-94%). The median progression-free survival (mPFS) was 6 months (95% CI = 1-29). Of the 13 patients who received the same EGFR-TKI, 1 patient in CR, 3 patients in PR, 8 patients in SD, and 2 patients in PD were observed. The DCR was 84.6%, and the mPFS was 5 months. Of the 14 patients who received another EGFR-TKI, 0 patient in CR, 6 patients in PR, 6 patients in SD, and 2 patients in PD were observed. The DCR was 85.7%, and the mPFS was 9.5 months. Significant difference was found between the 2 groups in progression-free survival but not in response rate or disease control rate.  Conclusion  Retreatment of EGFR-TKIs can be considered an option after failure of chemotherapy for patients who were previously controlled by EGFR-TKI treatment.