Erlotinib Plus Bevacizumab Phase ll Study in Patients with Advanced Non-small-Cell Lung Cancer (JO25567): Updated Safety Results

Terufumi Kato, Takashi Seto, Makoto Nishio, Koichi Goto, Noboru Yamamoto, Isamu Okamoto, Liang Tao, Wei Yu, Tarik Khaznadar, Kosei Tajima, Masahiko Shibata, Akihiro Seki, Nobuyuki Yamamoto

Research output: Contribution to journalArticle

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Abstract

Introduction: The phase II JO25567 study compared the efficacy and safety of erlotinib plus bevacizumab vs. erlotinib alone as first-line therapy for advanced epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Objective: Our objective is to provide updated analyses of safety and the assessment of manageability of specific adverse events. Methods: Patients with stage IIIB/IV or recurrent, non-squamous, EGFR mutation-positive NSCLC were randomized to receive erlotinib plus bevacizumab or erlotinib. The primary endpoint was progression-free survival. Adverse event frequency rates, predictability and manageability, reasons for discontinuation, time to onset, and outcomes of specific adverse events were analyzed. Results: The safety analysis population comprised 152 randomized patients (75 erlotinib plus bevacizumab; 77 erlotinib) who received at least one dose of study drug between February 2011 and March 2012. There was no difference in overall incidence of serious adverse events between arms, but more grade 3 or higher adverse events were reported with erlotinib plus bevacizumab (90.7%) than with erlotinib (53.2%), primarily due to grade 3 hypertension. Hypertension was controllable with antihypertensive medications in most cases. Proteinuria and bleeding were also more frequently reported with erlotinib plus bevacizumab than with erlotinib but were manageable and did not lead to early discontinuations. Conclusions: The addition of bevacizumab to erlotinib prolonged progression-free survival in EGFR mutation-positive NSCLC. Follow-up safety data were consistent with the known safety profiles of both erlotinib and bevacizumab in NSCLC; this combination appeared to be manageable, and treatment was well tolerated. JapicCTI-111390.

Original languageEnglish
Pages (from-to)229-237
Number of pages9
JournalDrug Safety
Volume41
Issue number2
DOIs
Publication statusPublished - Feb 1 2018

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Non-Small Cell Lung Carcinoma
Cells
Safety
Epidermal Growth Factor Receptor
Mutation
Disease-Free Survival
Erlotinib Hydrochloride
Bevacizumab
Hypertension
Proteinuria
Antihypertensive Agents
Hemorrhage

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology
  • Pharmacology (medical)

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Erlotinib Plus Bevacizumab Phase ll Study in Patients with Advanced Non-small-Cell Lung Cancer (JO25567) : Updated Safety Results. / Kato, Terufumi; Seto, Takashi; Nishio, Makoto; Goto, Koichi; Yamamoto, Noboru; Okamoto, Isamu; Tao, Liang; Yu, Wei; Khaznadar, Tarik; Tajima, Kosei; Shibata, Masahiko; Seki, Akihiro; Yamamoto, Nobuyuki.

In: Drug Safety, Vol. 41, No. 2, 01.02.2018, p. 229-237.

Research output: Contribution to journalArticle

Kato, T, Seto, T, Nishio, M, Goto, K, Yamamoto, N, Okamoto, I, Tao, L, Yu, W, Khaznadar, T, Tajima, K, Shibata, M, Seki, A & Yamamoto, N 2018, 'Erlotinib Plus Bevacizumab Phase ll Study in Patients with Advanced Non-small-Cell Lung Cancer (JO25567): Updated Safety Results', Drug Safety, vol. 41, no. 2, pp. 229-237. https://doi.org/10.1007/s40264-017-0596-0
Kato, Terufumi ; Seto, Takashi ; Nishio, Makoto ; Goto, Koichi ; Yamamoto, Noboru ; Okamoto, Isamu ; Tao, Liang ; Yu, Wei ; Khaznadar, Tarik ; Tajima, Kosei ; Shibata, Masahiko ; Seki, Akihiro ; Yamamoto, Nobuyuki. / Erlotinib Plus Bevacizumab Phase ll Study in Patients with Advanced Non-small-Cell Lung Cancer (JO25567) : Updated Safety Results. In: Drug Safety. 2018 ; Vol. 41, No. 2. pp. 229-237.
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