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

Tianhong Li, Bilal Piperdi, William V. Walsh, Mimi Kim, Laurel A Beckett, Rasim Gucalp, Missak Haigentz, Venu G. Bathini, Huiyu Wen, Kaili Zhou, Patricia B. Pasquinelli, Srikanth Gajavelli, Meera Sreedhara, Xianhong Xie, Primo N Lara, David R Gandara, Roman Perez-Soler

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: 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 Methods: Patients 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. Results: Of 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. Conclusion: In 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.

Original languageEnglish (US)
JournalClinical Lung Cancer
DOIs
StateAccepted/In press - Jun 19 2016

Keywords

  • EGFR wild type
  • Multiplex genotyping
  • Plasma circulating tumor DNA
  • Randomized phase 2 study
  • Second line

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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