Phase II trial of gefitinib in combination with bevacizumab as first-line therapy for advanced non-small cell lung cancer with activating EGFR gene mutations: The okayama lung cancer study group trial 1001

Eiki Ichihara, Katsuyuki Hotta, Naoyuki Nogami, Shoichi Kuyama, Daizo Kishino, Masanori Fujii, Toshiyuki Kozuki, Masahiro Tabata, Daijiro Harada, Kenichi Chikamori, Keisuke Aoe, Hiroshi Ueoka, Shinobu Hosokawa, Akihiro Bessho, Akiko Hisamoto-Sato, Toshio Kubo, Isao Oze, Nagio Takigawa, Mitsune Tanimoto, Katsuyuki Kiura

Research output: Contribution to journalArticle

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Abstract

Purpose: Whether bevacizumab enhances the effect of the epidermal growth factor receptor (EGFR) inhibitor gefitinib on EGFR mutant non-small cell lung cancers (NSCLCs) remains unknown. We conducted a phase II trial to investigate the efficacy and safety of gefitinib when combined with bevacizumab as first-line therapy in patients with advanced NSCLC harboring EGFR gene mutations. Methods: In this trial, 42 patients with a performance status of 0 to 2 received gefitinib (250 mg/d) and bevacizumab (15 mg/kg, every 3 weeks). The primary end point of this study was the 1-year progression-free survival (PFS) rate. We assumed that a 1-year PFS rate of 55% would indicate potential usefulness and that a 1-year PFS rate of 40% would constitute the lower limit of interest. Results: Forty-two patients were enrolled in the study with a median age of 73 (range 42-86) years. Activating EGFR gene mutations included exon 19 deletion (57%) and L858R point mutations in exon 21 (38%). The objective response rate was 73.8% and included two complete responses. The 1-year PFS rate and median PFS time were 56.7% (95% confidence interval [CI] 39.9-70.5) and 14.4 months (95% CI 10.1-19.2), respectively. The median PFS differed significantly between EGFR exon 19 deletion and the L858R point mutation (18.0 versus 9.4 months, respectively; p = 0.006). The median overall survival had not yet been reached. Severe adverse events included grade 3 skin rash (15%), hypertension (17%), aspartate transaminase/alanine aminotransferase elevation (17%), proteinuria (7%), intracranial hemorrhage (2%), and grade 4 perforation of the digestive tract (2%). There were no treatment-related deaths. Conclusion: Gefitinib in combination with bevacizumab as first-line therapy seems to be a favorable and well-tolerated treatment for patients with advanced NSCLC with activating EGFR gene mutations, especially those with EGFR exon 19 deletion mutations, although the primary end point was not met because the lower limit of the CI was less than 40%.

Original languageEnglish
Pages (from-to)486-491
Number of pages6
JournalJournal of Thoracic Oncology
Volume10
Issue number3
DOIs
Publication statusPublished - Mar 30 2015

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erbB-1 Genes
Non-Small Cell Lung Carcinoma
Disease-Free Survival
Lung Neoplasms
Epidermal Growth Factor Receptor
Mutation
Exons
Survival Rate
Confidence Intervals
Point Mutation
Therapeutics
Intracranial Hemorrhages
Sequence Deletion
Aspartate Aminotransferases
Exanthema
Alanine Transaminase
Proteinuria
Gastrointestinal Tract
gefitinib
Bevacizumab

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Phase II trial of gefitinib in combination with bevacizumab as first-line therapy for advanced non-small cell lung cancer with activating EGFR gene mutations : The okayama lung cancer study group trial 1001. / Ichihara, Eiki; Hotta, Katsuyuki; Nogami, Naoyuki; Kuyama, Shoichi; Kishino, Daizo; Fujii, Masanori; Kozuki, Toshiyuki; Tabata, Masahiro; Harada, Daijiro; Chikamori, Kenichi; Aoe, Keisuke; Ueoka, Hiroshi; Hosokawa, Shinobu; Bessho, Akihiro; Hisamoto-Sato, Akiko; Kubo, Toshio; Oze, Isao; Takigawa, Nagio; Tanimoto, Mitsune; Kiura, Katsuyuki.

In: Journal of Thoracic Oncology, Vol. 10, No. 3, 30.03.2015, p. 486-491.

Research output: Contribution to journalArticle

Ichihara, Eiki ; Hotta, Katsuyuki ; Nogami, Naoyuki ; Kuyama, Shoichi ; Kishino, Daizo ; Fujii, Masanori ; Kozuki, Toshiyuki ; Tabata, Masahiro ; Harada, Daijiro ; Chikamori, Kenichi ; Aoe, Keisuke ; Ueoka, Hiroshi ; Hosokawa, Shinobu ; Bessho, Akihiro ; Hisamoto-Sato, Akiko ; Kubo, Toshio ; Oze, Isao ; Takigawa, Nagio ; Tanimoto, Mitsune ; Kiura, Katsuyuki. / Phase II trial of gefitinib in combination with bevacizumab as first-line therapy for advanced non-small cell lung cancer with activating EGFR gene mutations : The okayama lung cancer study group trial 1001. In: Journal of Thoracic Oncology. 2015 ; Vol. 10, No. 3. pp. 486-491.
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title = "Phase II trial of gefitinib in combination with bevacizumab as first-line therapy for advanced non-small cell lung cancer with activating EGFR gene mutations: The okayama lung cancer study group trial 1001",
abstract = "Purpose: Whether bevacizumab enhances the effect of the epidermal growth factor receptor (EGFR) inhibitor gefitinib on EGFR mutant non-small cell lung cancers (NSCLCs) remains unknown. We conducted a phase II trial to investigate the efficacy and safety of gefitinib when combined with bevacizumab as first-line therapy in patients with advanced NSCLC harboring EGFR gene mutations. Methods: In this trial, 42 patients with a performance status of 0 to 2 received gefitinib (250 mg/d) and bevacizumab (15 mg/kg, every 3 weeks). The primary end point of this study was the 1-year progression-free survival (PFS) rate. We assumed that a 1-year PFS rate of 55{\%} would indicate potential usefulness and that a 1-year PFS rate of 40{\%} would constitute the lower limit of interest. Results: Forty-two patients were enrolled in the study with a median age of 73 (range 42-86) years. Activating EGFR gene mutations included exon 19 deletion (57{\%}) and L858R point mutations in exon 21 (38{\%}). The objective response rate was 73.8{\%} and included two complete responses. The 1-year PFS rate and median PFS time were 56.7{\%} (95{\%} confidence interval [CI] 39.9-70.5) and 14.4 months (95{\%} CI 10.1-19.2), respectively. The median PFS differed significantly between EGFR exon 19 deletion and the L858R point mutation (18.0 versus 9.4 months, respectively; p = 0.006). The median overall survival had not yet been reached. Severe adverse events included grade 3 skin rash (15{\%}), hypertension (17{\%}), aspartate transaminase/alanine aminotransferase elevation (17{\%}), proteinuria (7{\%}), intracranial hemorrhage (2{\%}), and grade 4 perforation of the digestive tract (2{\%}). There were no treatment-related deaths. Conclusion: Gefitinib in combination with bevacizumab as first-line therapy seems to be a favorable and well-tolerated treatment for patients with advanced NSCLC with activating EGFR gene mutations, especially those with EGFR exon 19 deletion mutations, although the primary end point was not met because the lower limit of the CI was less than 40{\%}.",
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T1 - Phase II trial of gefitinib in combination with bevacizumab as first-line therapy for advanced non-small cell lung cancer with activating EGFR gene mutations

T2 - The okayama lung cancer study group trial 1001

AU - Ichihara, Eiki

AU - Hotta, Katsuyuki

AU - Nogami, Naoyuki

AU - Kuyama, Shoichi

AU - Kishino, Daizo

AU - Fujii, Masanori

AU - Kozuki, Toshiyuki

AU - Tabata, Masahiro

AU - Harada, Daijiro

AU - Chikamori, Kenichi

AU - Aoe, Keisuke

AU - Ueoka, Hiroshi

AU - Hosokawa, Shinobu

AU - Bessho, Akihiro

AU - Hisamoto-Sato, Akiko

AU - Kubo, Toshio

AU - Oze, Isao

AU - Takigawa, Nagio

AU - Tanimoto, Mitsune

AU - Kiura, Katsuyuki

PY - 2015/3/30

Y1 - 2015/3/30

N2 - Purpose: Whether bevacizumab enhances the effect of the epidermal growth factor receptor (EGFR) inhibitor gefitinib on EGFR mutant non-small cell lung cancers (NSCLCs) remains unknown. We conducted a phase II trial to investigate the efficacy and safety of gefitinib when combined with bevacizumab as first-line therapy in patients with advanced NSCLC harboring EGFR gene mutations. Methods: In this trial, 42 patients with a performance status of 0 to 2 received gefitinib (250 mg/d) and bevacizumab (15 mg/kg, every 3 weeks). The primary end point of this study was the 1-year progression-free survival (PFS) rate. We assumed that a 1-year PFS rate of 55% would indicate potential usefulness and that a 1-year PFS rate of 40% would constitute the lower limit of interest. Results: Forty-two patients were enrolled in the study with a median age of 73 (range 42-86) years. Activating EGFR gene mutations included exon 19 deletion (57%) and L858R point mutations in exon 21 (38%). The objective response rate was 73.8% and included two complete responses. The 1-year PFS rate and median PFS time were 56.7% (95% confidence interval [CI] 39.9-70.5) and 14.4 months (95% CI 10.1-19.2), respectively. The median PFS differed significantly between EGFR exon 19 deletion and the L858R point mutation (18.0 versus 9.4 months, respectively; p = 0.006). The median overall survival had not yet been reached. Severe adverse events included grade 3 skin rash (15%), hypertension (17%), aspartate transaminase/alanine aminotransferase elevation (17%), proteinuria (7%), intracranial hemorrhage (2%), and grade 4 perforation of the digestive tract (2%). There were no treatment-related deaths. Conclusion: Gefitinib in combination with bevacizumab as first-line therapy seems to be a favorable and well-tolerated treatment for patients with advanced NSCLC with activating EGFR gene mutations, especially those with EGFR exon 19 deletion mutations, although the primary end point was not met because the lower limit of the CI was less than 40%.

AB - Purpose: Whether bevacizumab enhances the effect of the epidermal growth factor receptor (EGFR) inhibitor gefitinib on EGFR mutant non-small cell lung cancers (NSCLCs) remains unknown. We conducted a phase II trial to investigate the efficacy and safety of gefitinib when combined with bevacizumab as first-line therapy in patients with advanced NSCLC harboring EGFR gene mutations. Methods: In this trial, 42 patients with a performance status of 0 to 2 received gefitinib (250 mg/d) and bevacizumab (15 mg/kg, every 3 weeks). The primary end point of this study was the 1-year progression-free survival (PFS) rate. We assumed that a 1-year PFS rate of 55% would indicate potential usefulness and that a 1-year PFS rate of 40% would constitute the lower limit of interest. Results: Forty-two patients were enrolled in the study with a median age of 73 (range 42-86) years. Activating EGFR gene mutations included exon 19 deletion (57%) and L858R point mutations in exon 21 (38%). The objective response rate was 73.8% and included two complete responses. The 1-year PFS rate and median PFS time were 56.7% (95% confidence interval [CI] 39.9-70.5) and 14.4 months (95% CI 10.1-19.2), respectively. The median PFS differed significantly between EGFR exon 19 deletion and the L858R point mutation (18.0 versus 9.4 months, respectively; p = 0.006). The median overall survival had not yet been reached. Severe adverse events included grade 3 skin rash (15%), hypertension (17%), aspartate transaminase/alanine aminotransferase elevation (17%), proteinuria (7%), intracranial hemorrhage (2%), and grade 4 perforation of the digestive tract (2%). There were no treatment-related deaths. Conclusion: Gefitinib in combination with bevacizumab as first-line therapy seems to be a favorable and well-tolerated treatment for patients with advanced NSCLC with activating EGFR gene mutations, especially those with EGFR exon 19 deletion mutations, although the primary end point was not met because the lower limit of the CI was less than 40%.

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