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 journalArticle

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

Fingerprint Dive into the research topics of 'Randomized Phase 2 Trial of Pharmacodynamic Separation of Pemetrexed and Intercalated Erlotinib Versus Pemetrexed Alone for Advanced Nonsquamous, Non-small-cell Lung Cancer'. Together they form a unique fingerprint.

  • Cite this

    Li, T., Piperdi, B., Walsh, W. V., Kim, M., Beckett, L. A., Gucalp, R., Haigentz, M., Bathini, V. G., Wen, H., Zhou, K., Pasquinelli, P. B., Gajavelli, S., Sreedhara, M., Xie, X., Lara, P. N., Gandara, D. R., & Perez-Soler, R. (Accepted/In press). Randomized Phase 2 Trial of Pharmacodynamic Separation of Pemetrexed and Intercalated Erlotinib Versus Pemetrexed Alone for Advanced Nonsquamous, Non-small-cell Lung Cancer. Clinical Lung Cancer. https://doi.org/10.1016/j.cllc.2016.10.003