1285P - A phase II trial of gefitinib in combination with bevacizumab as first-line therapy for advanced non-small-cell lung cancer with activating EGFR ge...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Pathology/Molecular Biology
Personalised Medicine
Presenter Naoyuki Nogami
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors N. Nogami1, E. Ichihara2, T. Kozuki3, T. Kubo2, D. Kishino4, S. Kuyama5, A. Bessho6, M. Fujii7, N. Takigawa8, K. Chikamori4, K. Aoe4, T. Nagata9, N. Fujimoto10, S. Hosokawa6, S. Harita11, H. Kamei12, H. Ueoka4, K. Hotta13, M. Tanimoto14, K. Kiura15
  • 1Thoracic Oncology, NHO Shikoku Cancer Center, 791-0280 - Matsuyama/JP
  • 2Respiratory Medicine, Okayama University Hospital, Okayama/JP
  • 3Thoracic Oncology, NHO Shikoku Cancer Center, Matsuyama/JP
  • 4Respiratory Medicine, NHO Yamaguchi-Ube Medical Center, Ube/JP
  • 5Respiratory Medicine, NHO Iwakuni Medical Center, Iwakuni/JP
  • 6Respiratory Medicine, Japanese Red Cross Okayama Hospital, Okayama/JP
  • 7Respiratory Medicine, Japanese Red Cross Kobe Hospital, Kobe/JP
  • 8General Internal Medicine 4, Kawasaki Medical School, Okayama/JP
  • 9Respiratory Medicine, Kagawa Rosai Hospital, Marugame/JP
  • 10Respiratory Medicine, Okayama Rosai Hospital, Okayama/JP
  • 11Respiratory Medicine, Chugoku Central Hospital, Fukuyama/JP
  • 12Thoracic Oncology, Sumitomo Besshi Hspital, Niihama/JP
  • 13Department Of Respiratory Medicine, Okayama University Hospital, 7008558 - Okayama/JP
  • 14General Internal Medicine Ⅱ, Okayama University Hospital, Okayama/JP
  • 15Department Of Respiratory Medicine, Okayama University Hospital, Okayama/JP

Abstract

Aim

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) such as gefitinib, erlotinib or afatinib are essential drugs for the treatment of advanced non-small cell lung cancer (NSCLC) with activating EGFR gene mutations. However, disease progression inevitably occurs around 10-12 months after EGFR-TKI treatment. Bevacizumab (Bmab) enhances the effect of cytotoxic chemotherapy with advanced NSCLC while it remains unknown whether Bmab enhances the effect of EGFR-TKIs on EGFR mutant NSCLC. We conducted a phase II trial to investigate the efficacy and safety of gefitinib when combined with Bmab as a first-line therapy in patients with advanced NSCLC harboring EGFR gene mutations.

Methods

In this trial, 42 patients with PS 0 to 2 received daily gefitinib (250mg/body) and Bmab (15mg/kg, every 3 weeks). The primary endpoint was 1-year progression-free survival (PFS) rate, and the secondary endpoints included response rate, PFS time, overall survival (OS) time and toxicity.

Results

The patients had a median age of 73 (range, 42-86), of whom 40% were male, 75% with PS 0-1, 79% in stage IV, and 21% with postoperative recurrence. As for the activating EGFR gene mutations, 57% of the patients had exon 19 deletion (del), 38% exon 21 point mutations (L858R), 2.5% exon 18 G719A, and 2.5% exon 21 G861Q. At the time of this analysis, 34 pts (81%) had dropped out of the protocol treatment, wherein 10 out of 42 pts (24%) discontinued it because of adverse events (AEs). The 1-year PFS rate was 56.7% (95% confidence interval: 39.9-70.5%), which did not meet the primary endpoint. The median PFS time (month) was 14.4 with a significant difference between those of exon 19 del (18.0) and L858R (9.4, p = 0.006). The objective response rate and disease control rate were 73.8% and 97.6%, respectively. The median OS was not yet reached. The severe AEs included grade 3 liver dysfunction (19%), hypertension (17%), acneiform (14%), proteinuria (7%), intracranial hemorrhage (3%), and grade 4 perforation of the digestive tract (3%), but no treatment-related death.

Conclusions

Gefitinib in combination with Bmab as a first line therapy seems a favorable and well-tolerated treatment for patients with advanced NSCLC with activating EGFR gene mutations, especially for those with exon 19 del mutations.

Disclosure

N. Nogami: Reseach funding; Astra Zeneca, Chugai-Pharma. Speaker fees for scientific meetings; Astra Zeneca, Chugai-Pharma; T. Kozuki: Reseach funding; Astra Zeneca, Chugai-Pharma. Speaker fees for scientific meetings; Astra Zeneca, Chugai-Pharma; N. Takigawa: Speaker fees for scientific meetings; Astra Zeneca, Chugai-Pharma; K. Hotta: Reseach funding; Astra Zeneca, Chugai-Pharma. Speaker fees for scientific meetings; Astra Zeneca, Chugai-Pharma; . Kiura: Reseach funding; Astra Zeneca, Chugai-Pharma. Speaker fees for scientific meetings; Astra Zeneca, Chugai-Pharma. All other authors have declared no conflicts of interest.