Lung Cancer 78 (2012) 239–244 Contents lists available at SciVerse ScienceDirect Lung Cancer j our na l ho me p age: www.elsevier.com/locate/lungcan Bevacizumab and erlotinib (BE) first-line therapy in advanced non-squamous non-small-cell lung cancer (NSCLC) (stage IIIB/IV) followed by platinum-based chemotherapy (CT) at disease progression: A multicenter phase II trial (SAKK 19/05) Francesco Zappa a,∗ , Cornelia Droege b , Daniel Betticher c , Roger von Moos d , Lukas Bubendorf b , Adrian Ochsenbein e , Oliver Gautschi e , Elisabeth Oppliger Leibundgut e , Patrizia Froesch a , Rolf Stahel f , Thomas Hess g , Daniel Rauch h , Petra Schmid i , Michael Mayer j , Susanne Crowe j , Peter Brauchli j , Karin Ribi k , Miklos Pless g , on behalf of the Swiss Group for Clinical Cancer Research (SAKK) a Oncology Institute of Southern Switzerland, Switzerland b University Hospital Basel, Switzerland c Kantonsspital Fribourg, Switzerland d Chur, Switzerland e University Hospital Bern, Switzerland f University Hospital Zürich, Switzerland g Kantonsspital Winterthur, Switzerland h Regionalspital Thun, Switzerland i Kantonsspital Aarau, Switzerland j SAKK Coordinating Center Bern, Switzerland k IBCSG Coordinating Center Bern, Switzerland a r t i c l e i n f o Article history: Received 24 April 2012 Received in revised form 5 August 2012 Accepted 28 August 2012 Keywords: Bevacizumab Erlotinib Non-squamous NSCLC Metastatic Translational research First-line regimen a b s t r a c t Purpose: This phase II trial aimed to evaluate feasibility and efficacy of a first-line combination of targeted therapies for advanced non-squamous NSCLC: bevacizumab (B) and erlotinib (E), followed by platinum- based CT at disease progression (PD). Methods: 103 patients with advanced non-squamous NSCLC were treated with B (15 mg/kg day 1 of each 21-day cycle) and E (150 mg daily) until PD or unacceptable toxicity. Upon PD patients received 6 cycles of CT (cisplatin/carboplatin and gemcitabine). The primary endpoint was disease stabilization rate (DSR) after 12 weeks of BE treatment. Results: 101 patients were evaluable. Under BE, DSR at week 12 was 54.5%. 73 patients had at least stable disease (SD), including 1 complete remission and 17 partial responses (PR). No unexpected toxicities were observed. Median time to progression (TTP) under BE was 4.1 months. 62 patients started CT; 35 received at least 4 cycles (6 PR, 32 SD). At a median follow-up of 36 months, median overall survival (OS) was 14.1 months. Conclusions: First-line BE treatment followed by a fixed CT regimen at PD is feasible with acceptable toxicity and activity. In a non-squamous NSCLC population unselected for EGFR status, we found OS rates similar to standard CT. © 2012 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Standard first-line treatment for patients with advanced NSCLC consists of platinum-based CT in combination with agents such as vinorelbine, gemcitabine, paclitaxel, docetaxel and pemetrexed. ∗ Corresponding author at: Oncology Unit, Clinica Luganese SA, Via Moncucco 10, 6900 Lugano-TI, Switzerland. Tel.: +41 919608705; fax: +41 919608580. E-mail address: francesco.zappa@clinicaluganese.ch (F. Zappa). However, these CTs cause variable toxicities for a modest survival benefit [1,2]. Various targeted agents are under investigation [3]; the VEGF-targeted recombinant humanized monoclonal antibody bevacizumab has shown progression-free survival (PFS) and overall survival (OS) benefits when combined with CT for the treatment of advanced non-squamous NSCLC patients, with little additional tox- icity [4–8]. Erlotinib, an orally active inhibitor of EGFR-associated tyrosine kinase, is generally safe and well tolerated, and its role as single agent in second- and third-line therapy is well 0169-5002/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.lungcan.2012.08.017