Tags

Type your tag names separated by a space and hit enter

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.
J Thorac Oncol 2015; 10(3):486-91JT

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%.

Authors+Show Affiliations

*Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan; †Department of Hematology/Oncology, Vanderbilt Vanderbilt University Medical Center, Nashville, TN; ‡Department of Respiratory Medicine, NHO Shikoku Cancer Center, Matsuyama, Japan; §Department of Respiratory Medicine, NHO Iwakuni Clinical Center, Iwakuni, Japan; ‖Department of Medical Oncology, NHO Yamaguchi-Ube Medical Center, Ube, Japan; ¶Department of Respiratory Internal Medicine, Japanese Red Cross Kobe Hospital, Kobe, Japan; #Division of Clinical Oncology, Sumitomo Besshi Hospital, Niihama, Japan; **Department of Clinical Research, NHO Yamaguchi-Ube Medical Center, Ube, Japan; ††Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital, Okayama, Japan; ‡‡Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan; and §§Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Multicenter Study

Language

eng

PubMed ID

25695221

Citation

Ichihara, Eiki, et al. "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." Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer, vol. 10, no. 3, 2015, pp. 486-91.
Ichihara E, Hotta K, Nogami N, et al. 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. J Thorac Oncol. 2015;10(3):486-91.
Ichihara, E., Hotta, K., Nogami, N., Kuyama, S., Kishino, D., Fujii, M., ... Kiura, K. (2015). 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. Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer, 10(3), pp. 486-91. doi:10.1097/JTO.0000000000000434.
Ichihara E, et al. 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. J Thorac Oncol. 2015;10(3):486-91. PubMed PMID: 25695221.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR 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: 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 - 2015/2/20/entrez PY - 2015/2/20/pubmed PY - 2016/3/10/medline SP - 486 EP - 91 JF - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JO - J Thorac Oncol VL - 10 IS - 3 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%. SN - 1556-1380 UR - https://www.unboundmedicine.com/medline/citation/25695221/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1556-0864(15)31657-9 DB - PRIME DP - Unbound Medicine ER -