1286P - EGFR-tyrosine kinase inhibitor (TKI) rechallenge with bevacizumab in EGFR-mutant non-small cell lung cancer (NSCLC)

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 Kyoko Otsuka
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors K. Otsuka1, A. Hata2, R. Kato1, J. Takeshita1, C. Okuda1, R. Kaji1, K. Masago1, S. Fujita1, N. Katakami3
  • 1Integrated Oncology, Institute of Biomedical Research and Innovation, 650-0047 - Kobe/JP
  • 2Integrated Oncology, Institute of Biomedical Research and Innovation Hospital, Kobe/JP
  • 3Division Of Integrated Oncology, Institute of Biomedical Research and Innovation, 650-0047 - Kobe/JP

Abstract

Aim

Several reports demonstrated efficacies of EGFR-TKI rechallenge in EGFR-mutant NSCLC, but the efficacies were only moderate (response rate [RR], 0-10% disease control rate [DCR], 20-30%, and progression-free survival [PFS], 2-3 months). Some preclinical studies suggested synergistic effects of bevacizumab and EGFR-TKI in TKI-resistant models. The aim of our study was to evaluate the efficacy and safety of EGFR-TKI rechallenge with bevacizumab after acquired resistance to TKI in EGFR-mutant NSCLC.

Methods

Between January 2010 and January 2014, twenty-one NSCLC patients, previously treated with EGFR-TKIs, received EGFR-TKI rechallenge in combination with bevacizumab. We retrospectively evaluated the RR, DCR, PFS, overall survival (OS), and safety. Re-biopsy was performed in all cases to examine T790M resistant mutation status. The efficacy was compared between T790M-positive and –negative populations.

Results

The eligible 21 patients were all EGFR mutant. Previous EGFR-TKI treatments were 8 gefitinib, 11 erlotinib, and 2 afatinib. 11 patients had EGFR-TKIs rechallenge with bevacizumab successively without interval, and 10 patients received same after 1-4 intervening systemic regimens. EGFR-TKIs for rechallenge in combination with bevacizumab were 2 gefitinib and 19 erlotinib. Two (9.5%) had partial response, 12 (90%) had stable disease. The RR and DCR were 9.5% and 95%, respectively. The median PFS was 3.6 months (95% confidence interval (CI); 2.5-14.9 months), and the median OS was 13.5 months (95% CI; 9.7-21 months). On re-biopsy, 6 patients had T790M with the initial sensitive mutation. The RR, DCR, median PFS and median OS for T790M positive vs negative were 0% vs 13% (p = 0.23), 100% vs 93% (p = 0.40), 3.6 months vs 4.1 months (p = 0.78), and 15.1 months vs 13.5 months (p = 0.656), respectively. Severe adverse events (≧grade 3) were as follows: grade 3 hypertension in one (4.8%) and grade 3 anemia in one patient (4.8%).

Conclusions

EGFR-TKI rechallenge with bevacizumab demonstrated higher DCR and modestly longer PFS, compared with EGFR-TKI monotherapy rechallenge. Its activity did not differ according to T790M status. EGFR-TKI rechallenge with bevacizumab can be a therapeutic option for EGFR-mutant NSCLC with acquired resistance regardless of resistant mechanisms.

Disclosure

All authors have declared no conflicts of interest.