171P - Carboplatin–paclitaxel bevacizumab followed by the addition of erlotinib to bevacizumab beyond progression in patients with advanced NSCLC

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Cytotoxic agents
Non-small-cell lung cancer
Therapy
Biological therapy
Presenter Hester Van Groningen
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors H. Van Groningen, A. Timmer-Bonte, D. Van den Hurk, M. Dohmen, C. Smits-Van der Graaf, M. Van der Drift
  • Pulmonology, Radboud University Medical Centre Nijmegen, 6500 HB - Nijmegen/NL

Abstract

Background

The vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways represent 2 clinically validated and interrelated targets for NSCLC. Preclinical studies have shown that VEGF and EGFR inhibitors, e.g. erlotinib (E) can have additive effects. This open label single centre phase II study investigated the efficacy of 2nd line E plus bevacizumab (B) subsequent to a 1st line combination of carboplatin, paclitaxel and bevacizumab (CPB).

Methods

Previously untreated patients with advanced non-squamous NSCLC received 1st line treatment with 3-weekly C (AUC 6 i.v. day 1), P (200 mg/m2 i.v. day 1) and B (15 mg/kg i.v. day 1) for a maximum of 4 cycles after which monotherapy 3-weekly B continued. Response evaluation was performed every 6 weeks. At progression B was continued and 2nd E (150 mg/day orally) was added. Both EGFR-mutated as wild type EGFR patients were included. The primary objective of the study was to assess the efficacy, defined as disease control rate (DCR) (CR+PR+SD according to RECIST 1.0) at 12 weeks treatment with BE. Secondary objectives were the efficacy of CPB defined as DCR and Progression Free Survival (PFS), efficacy of BE defined as Time To Progression (TTP) and Overall Survival (OS).

Results

Informed consent was obtained from 35 patients (pts), 32 started therapy. Only 2 patients had an EGFR mutation. 26 patients (81%) received 4 cycles of CPB, 87.5% had a response. 26 pts received maintenance B, with a median of 6.5 cycles. 21 patients started 2nd line BE, for a median number of 2 cycles. At 12 weeks BE, DCR was 42.9% and the trial met its early stopping rule. Median PFS on 1st line was 9.1 months. Median TTP on 2nd line was 3.6 months. Median OS was 15.2 months (with a maximum of 56.2). Only 1 patient with an EGFR mutation received BE, with a TTP on 2nd line of 14.9 months and an OS of 47.9 months.

Conclusions

The administration of 2nd line E to B beyond progression in an unselected population does not result in clinical benefit. OS was as can be expected; as well as PFS on 1st line treatment. Further research on the efficacy of combined EGFR and VEGF-inhibition in NSCLC should take EGFR mutation status into account.

Clinical trial identification

Protocol ULCN 0107: NCT00702975

Legal entity responsible for the study

Radboudumc

Funding

Roche

Disclosure

A. Timmer-Bonte, C. Smits-Van der Graaf, M. Van der Drift: Roche paid a fee to the pulmonology ward where this author worked at the time of this study. All other authors have declared no conflicts of interest.