Randomized Phase 2 Trial of Pharmacodynamic Separation of Pemetrexed and Intercalated Erlotinib Versus Pemetrexed Alone for Advanced Nonsquamous, Non-small-cell Lung Cancer

详细信息    查看全文

• 作者：Tianhong Li¹ ; ⁶ ; ^{thli@ucdavis.edu} ; Bilal Piperdi² ; William V. Walsh³ ; Mimi Kim⁴ ; Laurel A. Beckett¹ ; ⁵ ; Rasim Gucalp² ; Missak Haigentz Jr.² ; Venu G. Bathini³ ; Huiyu Wen¹ ; Kaili Zhou¹ ; Patricia B. Pasquinelli¹ ; Srikanth Gajavelli² ; Meera Sreedhara³ ; Xianhong Xie⁴ ; Primo N. Lara Jr.¹ ; David R. Gandara¹ ; Roman Perez-Soler²
• 关键词：EGFR wild type ; Multiplex genotyping ; Plasma circulating tumor DNA ; Randomized phase 2 study ; Second line
• 刊名：Clinical Lung Cancer
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：18
• 期：1
• 页码：60-67
• 全文大小：537 K
• 卷排序：18

文摘

Pharmacodynamic separation of pemetrexed and erlotinib avoids negative cellular interactions and results in antitumor synergy in erlotinib-resistant non–small-cell lung cancer (NSCLC) cells, independent of EGFR (epidermal growth factor receptor) genotype.Patients and MethodsPatients with platinum-treated metastatic nonsquamous NSCLC were randomly assigned 1:2 to pemetrexed alone (500 mg/m2 provided intravenously on day 1) or pemetrexed followed by erlotinib (150 mg provided orally once daily on days 2-17) every 21 days. EGFR genotype was centrally confirmed by Sequenom multiplex oncogenotyping assay. The primary end point was progression-free survival (PFS), which would be considered promising for future study if median PFS was ≥ 4.5 months.ResultsOf 83 patients enrolled, 79 were randomized to either pemetrexed alone (n = 27) or in combination (n = 52). Fifty-nine (79%) of 75 eligible patients had tumors with confirmed EGFR genotype: 7 with activating mutations and 52 wild type. Median PFS was 4.7 and 2.9 months in the combination and pemetrexed-alone groups, respectively. In patients with EGFR wild-type tumors, median PFS was 5.3 and 3.5 months in the combination and pemetrexed-alone groups, respectively. Objective response rate (29% vs. 10%, P = .17), 6-month PFS (45% vs. 29%, P = .26), and 12-month PFS (23% vs. 10%, P = .28) were all higher in the combination arm. Rash (67% vs. 26%, P = .0007) and diarrhea (44% vs. 11%, P = .003) were significantly more common in the combination arm.ConclusionIn patients with unselected or EGFR wild-type advanced nonsquamous NSCLC, pharmacodynamic separation of pemetrexed and intercalated erlotinib had promising antitumor activity without new safety concerns. The combination merits further evaluation as maintenance or second-line therapy against new standards in patients with EGFR wild-type advanced NSCLC.