Halmos Balazs, Pennell Nathan A, Fu Pingfu, Saad Shumaila, Gadgeel Shirish, Otterson Gregory A, Mekhail Tarek, Snell Michael, Kuebler J Philip, Sharma Neelesh, Dowlati Afshin
Division of Hematology/Oncology, Herbert Irving Comprehensive Cancer Center, New York Presbyterian Hospital-Columbia University Medical Center, New York, New York, USA
Cleveland Clinic Foundation, Taussig Cancer Center, Cleveland, Ohio, USA.
Oncologist. 2015 Nov;20(11):1298-303. doi: 10.1634/theoncologist.2015-0136. Epub 2015 Aug 25.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy is clearly beneficial in patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). However, acquired resistance develops uniformly and the benefit of continuation of EGFR TKI therapy beyond progression remains unclear.
This was a randomized phase II study of chemotherapy (arm A: pemetrexed or docetaxel) versus chemotherapy plus erlotinib (ERL) (arm B) in patients with progressive NSCLC following clinical benefit from erlotinib. In arm B, chemotherapy was given with erlotinib at an oral daily dose of 150 mg on days 2-19 of each cycle to minimize negative pharmacodynamic interactions. The primary endpoint was that continuation of erlotinib in this patient population could extend progression-free survival (PFS) by 50%.
A total of 46 patients were randomized (arm A: 24; arm B: 22). Patient characteristics were well balanced except there were more female patients in arm A (p = .075). The median PFS of patients in arm A was 5.5 months and for those in arm B, 4.4 months (p = .699). The response rates were 13% and 16% in arms A and B, respectively (p = .79). EGFR status data were available for 39 of the 46 patients and no significant difference in PFS was seen for continuing ERL beyond progression in mutation-positive patients. Substantially more toxicity was seen in arm B than arm A.
There was added toxicity but no benefit with the continuation of ERL beyond progression along with chemotherapy as compared with chemotherapy alone.
The benefits of continuing erlotinib upon progression alongside conventional chemotherapy are unclear. This randomized phase II study, initiated prior to the establishment of routine epidermal growth factor receptor (EGFR) mutation testing, addressed this clinically relevant issue through randomizing patients with prior clinical benefit from erlotinib (thereby enriching for EGFR-mutated tumors) upon progression in the second- or third-line setting to conventional chemotherapy (single-agent pemetrexed or docetaxel) with or without continued erlotinib. The results showed no benefit to continuing erlotinib beyond progression, while significantly more side effects were noted in the combination arm. Along with other recently presented study findings, these results argue against the routine practice of continuing erlotinib in this setting.
表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）治疗对晚期EGFR突变的非小细胞肺癌（NSCLC）患者明显有益。然而，获得性耐药会一致出现，且EGFR TKI治疗在疾病进展后继续使用的益处仍不明确。
这是一项随机II期研究，对比化疗（A组：培美曲塞或多西他赛）与化疗联合厄洛替尼（ERL）（B组），研究对象为在接受厄洛替尼治疗获得临床获益后疾病进展的NSCLC患者。在B组中，化疗与厄洛替尼联合使用，厄洛替尼每日口服剂量为150 mg，在每个周期的第2 - 19天给药，以尽量减少负面的药效学相互作用。主要终点是在该患者群体中继续使用厄洛替尼可将无进展生存期（PFS）延长50%。
共有46例患者被随机分组（A组：24例；B组：22例）。除A组女性患者更多外（p = 0.075），患者特征均衡。A组患者的中位PFS为5.5个月，B组为4.4个月（p = 0.699）。A组和B组的缓解率分别为13%和16%（p = 0.79）。46例患者中有39例可获得EGFR状态数据，对于突变阳性患者，疾病进展后继续使用ERL，PFS无显著差异。B组的毒性明显高于A组。
与单纯化疗相比，疾病进展后继续使用ERL联合化疗会增加毒性，但无益处。
疾病进展后继续使用厄洛替尼联合传统化疗的益处尚不清楚。这项随机II期研究在常规表皮生长因子受体（EGFR）突变检测确立之前启动，通过将在二线或三线治疗中疾病进展且之前接受厄洛替尼治疗获得临床获益的患者（从而富集EGFR突变肿瘤）随机分为接受传统化疗（单药培美曲塞或多西他赛）联合或不联合继续使用厄洛替尼，解决了这一临床相关问题。结果显示疾病进展后继续使用厄洛替尼无益处，而联合治疗组的副作用明显更多。连同其他近期公布的研究结果，这些结果反对在这种情况下常规继续使用厄洛替尼。
