Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): An open-label, randomised, multicentre, phase 2 study

Takashi Seto, Terufumi Kato, Makoto Nishio, Koichi Goto, Shinji Atagi, Yukio Hosomi, Noboru Yamamoto, Toyoaki Hida, Makoto Maemondo, Kazuhiko Nakagawa, Seisuke Nagase, Isamu Okamoto, Takeharu Yamanaka, Kosei Tajima, Ryosuke Harada, Masahiro Fukuoka, Nobuyuki Yamamoto

Research output: Contribution to journalArticle

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Abstract

Background: With use of EGFR tyrosine-kinase inhibitor monotherapy for patients with activating EGFR mutation-positive non-small-cell lung cancer (NSCLC), median progression-free survival has been extended to about 12 months. Nevertheless, new strategies are needed to further extend progression-free survival and overall survival with acceptable toxicity and tolerability for this population. We aimed to compare the efficacy and safety of the combination of erlotinib and bevacizumab compared with erlotinib alone in patients with non-squamous NSCLC with activating EGFR mutation-positive disease. Methods: In this open-label, randomised, multicentre, phase 2 study, patients from 30 centres across Japan with stage IIIB/IV or recurrent non-squamous NSCLC with activating EGFR mutations, Eastern Cooperative Oncology Group performance status 0 or 1, and no previous chemotherapy for advanced disease received erlotinib 150 mg/day plus bevacizumab 15 mg/kg every 3 weeks or erlotinib 150 mg/day monotherapy as a first-line therapy until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, as determined by an independent review committee. Randomisation was done with a dynamic allocation method, and the analysis used a modified intention-to-treat approach, including all patients who received at least one dose of study treatment and had tumour assessment at least once after randomisation. This study is registered with the Japan Pharmaceutical Information Center, number JapicCTI-111390. Findings: Between Feb 21, 2011, and March 5, 2012, 154 patients were enrolled. 77 were randomly assigned to receive erlotinib and bevacizumab and 77 to erlotinib alone, of whom 75 patients in the erlotinib plus bevacizumab group and 77 in the erlotinib alone group were included in the efficacy analyses. Median progression-free survival was 16·0 months (95% CI 13·9-18·1) with erlotinib plus bevacizumab and 9·7 months (5·7-11·1) with erlotinib alone (hazard ratio 0·54, 95% CI 0·36-0·79; log-rank test p=0·0015). The most common grade 3 or worse adverse events were rash (19 [25%] patients in the erlotinib plus bevacizumab group vs 15 [19%] patients in the erlotinib alone group), hypertension (45 [60%] vs eight [10%]), and proteinuria (six [8%] vs none). Serious adverse events occurred at a similar frequency in both groups (18 [24%] patients in the erlotinib plus bevacizumab group and 19 [25%] patients in the erlotinib alone group). Interpretation: Erlotinib plus bevacizumab combination could be a new first-line regimen in EGFR mutation-positive NSCLC. Further investigation of the regimen is warranted. Funding: Chugai Pharmaceutical Co Ltd.

Original languageEnglish
Pages (from-to)1236-1244
Number of pages9
JournalThe Lancet Oncology
Volume15
Issue number11
DOIs
Publication statusPublished - Oct 1 2014

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Non-Small Cell Lung Carcinoma
Mutation
Therapeutics
Disease-Free Survival
Bevacizumab
Erlotinib Hydrochloride
Random Allocation
Japan
Information Centers
Advisory Committees
Exanthema
Proteinuria
Pharmaceutical Preparations
Protein-Tyrosine Kinases
Disease Progression

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567) : An open-label, randomised, multicentre, phase 2 study. / Seto, Takashi; Kato, Terufumi; Nishio, Makoto; Goto, Koichi; Atagi, Shinji; Hosomi, Yukio; Yamamoto, Noboru; Hida, Toyoaki; Maemondo, Makoto; Nakagawa, Kazuhiko; Nagase, Seisuke; Okamoto, Isamu; Yamanaka, Takeharu; Tajima, Kosei; Harada, Ryosuke; Fukuoka, Masahiro; Yamamoto, Nobuyuki.

In: The Lancet Oncology, Vol. 15, No. 11, 01.10.2014, p. 1236-1244.

Research output: Contribution to journalArticle

Seto, T, Kato, T, Nishio, M, Goto, K, Atagi, S, Hosomi, Y, Yamamoto, N, Hida, T, Maemondo, M, Nakagawa, K, Nagase, S, Okamoto, I, Yamanaka, T, Tajima, K, Harada, R, Fukuoka, M & Yamamoto, N 2014, 'Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): An open-label, randomised, multicentre, phase 2 study', The Lancet Oncology, vol. 15, no. 11, pp. 1236-1244. https://doi.org/10.1016/S1470-2045(14)70381-X
Seto, Takashi ; Kato, Terufumi ; Nishio, Makoto ; Goto, Koichi ; Atagi, Shinji ; Hosomi, Yukio ; Yamamoto, Noboru ; Hida, Toyoaki ; Maemondo, Makoto ; Nakagawa, Kazuhiko ; Nagase, Seisuke ; Okamoto, Isamu ; Yamanaka, Takeharu ; Tajima, Kosei ; Harada, Ryosuke ; Fukuoka, Masahiro ; Yamamoto, Nobuyuki. / Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567) : An open-label, randomised, multicentre, phase 2 study. In: The Lancet Oncology. 2014 ; Vol. 15, No. 11. pp. 1236-1244.
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TY - JOUR

T1 - Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567)

T2 - An open-label, randomised, multicentre, phase 2 study

AU - Seto, Takashi

AU - Kato, Terufumi

AU - Nishio, Makoto

AU - Goto, Koichi

AU - Atagi, Shinji

AU - Hosomi, Yukio

AU - Yamamoto, Noboru

AU - Hida, Toyoaki

AU - Maemondo, Makoto

AU - Nakagawa, Kazuhiko

AU - Nagase, Seisuke

AU - Okamoto, Isamu

AU - Yamanaka, Takeharu

AU - Tajima, Kosei

AU - Harada, Ryosuke

AU - Fukuoka, Masahiro

AU - Yamamoto, Nobuyuki

PY - 2014/10/1

Y1 - 2014/10/1

N2 - Background: With use of EGFR tyrosine-kinase inhibitor monotherapy for patients with activating EGFR mutation-positive non-small-cell lung cancer (NSCLC), median progression-free survival has been extended to about 12 months. Nevertheless, new strategies are needed to further extend progression-free survival and overall survival with acceptable toxicity and tolerability for this population. We aimed to compare the efficacy and safety of the combination of erlotinib and bevacizumab compared with erlotinib alone in patients with non-squamous NSCLC with activating EGFR mutation-positive disease. Methods: In this open-label, randomised, multicentre, phase 2 study, patients from 30 centres across Japan with stage IIIB/IV or recurrent non-squamous NSCLC with activating EGFR mutations, Eastern Cooperative Oncology Group performance status 0 or 1, and no previous chemotherapy for advanced disease received erlotinib 150 mg/day plus bevacizumab 15 mg/kg every 3 weeks or erlotinib 150 mg/day monotherapy as a first-line therapy until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, as determined by an independent review committee. Randomisation was done with a dynamic allocation method, and the analysis used a modified intention-to-treat approach, including all patients who received at least one dose of study treatment and had tumour assessment at least once after randomisation. This study is registered with the Japan Pharmaceutical Information Center, number JapicCTI-111390. Findings: Between Feb 21, 2011, and March 5, 2012, 154 patients were enrolled. 77 were randomly assigned to receive erlotinib and bevacizumab and 77 to erlotinib alone, of whom 75 patients in the erlotinib plus bevacizumab group and 77 in the erlotinib alone group were included in the efficacy analyses. Median progression-free survival was 16·0 months (95% CI 13·9-18·1) with erlotinib plus bevacizumab and 9·7 months (5·7-11·1) with erlotinib alone (hazard ratio 0·54, 95% CI 0·36-0·79; log-rank test p=0·0015). The most common grade 3 or worse adverse events were rash (19 [25%] patients in the erlotinib plus bevacizumab group vs 15 [19%] patients in the erlotinib alone group), hypertension (45 [60%] vs eight [10%]), and proteinuria (six [8%] vs none). Serious adverse events occurred at a similar frequency in both groups (18 [24%] patients in the erlotinib plus bevacizumab group and 19 [25%] patients in the erlotinib alone group). Interpretation: Erlotinib plus bevacizumab combination could be a new first-line regimen in EGFR mutation-positive NSCLC. Further investigation of the regimen is warranted. Funding: Chugai Pharmaceutical Co Ltd.

AB - Background: With use of EGFR tyrosine-kinase inhibitor monotherapy for patients with activating EGFR mutation-positive non-small-cell lung cancer (NSCLC), median progression-free survival has been extended to about 12 months. Nevertheless, new strategies are needed to further extend progression-free survival and overall survival with acceptable toxicity and tolerability for this population. We aimed to compare the efficacy and safety of the combination of erlotinib and bevacizumab compared with erlotinib alone in patients with non-squamous NSCLC with activating EGFR mutation-positive disease. Methods: In this open-label, randomised, multicentre, phase 2 study, patients from 30 centres across Japan with stage IIIB/IV or recurrent non-squamous NSCLC with activating EGFR mutations, Eastern Cooperative Oncology Group performance status 0 or 1, and no previous chemotherapy for advanced disease received erlotinib 150 mg/day plus bevacizumab 15 mg/kg every 3 weeks or erlotinib 150 mg/day monotherapy as a first-line therapy until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, as determined by an independent review committee. Randomisation was done with a dynamic allocation method, and the analysis used a modified intention-to-treat approach, including all patients who received at least one dose of study treatment and had tumour assessment at least once after randomisation. This study is registered with the Japan Pharmaceutical Information Center, number JapicCTI-111390. Findings: Between Feb 21, 2011, and March 5, 2012, 154 patients were enrolled. 77 were randomly assigned to receive erlotinib and bevacizumab and 77 to erlotinib alone, of whom 75 patients in the erlotinib plus bevacizumab group and 77 in the erlotinib alone group were included in the efficacy analyses. Median progression-free survival was 16·0 months (95% CI 13·9-18·1) with erlotinib plus bevacizumab and 9·7 months (5·7-11·1) with erlotinib alone (hazard ratio 0·54, 95% CI 0·36-0·79; log-rank test p=0·0015). The most common grade 3 or worse adverse events were rash (19 [25%] patients in the erlotinib plus bevacizumab group vs 15 [19%] patients in the erlotinib alone group), hypertension (45 [60%] vs eight [10%]), and proteinuria (six [8%] vs none). Serious adverse events occurred at a similar frequency in both groups (18 [24%] patients in the erlotinib plus bevacizumab group and 19 [25%] patients in the erlotinib alone group). Interpretation: Erlotinib plus bevacizumab combination could be a new first-line regimen in EGFR mutation-positive NSCLC. Further investigation of the regimen is warranted. Funding: Chugai Pharmaceutical Co Ltd.

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