PMID- 23790468 OWN - NLM STAT- MEDLINE DCOM- 20140408 LR - 20211203 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 81 IP - 3 DP - 2013 Sep TI - Phase II study of pemetrexed and cisplatin plus cetuximab followed by pemetrexed and cetuximab maintenance therapy in patients with advanced nonsquamous non-small cell lung cancer. PG - 428-434 LID - S0169-5002(13)00222-5 [pii] LID - 10.1016/j.lungcan.2013.05.010 [doi] AB - OBJECTIVES: The aim was to determine if combined pemetrexed, cisplatin, and cetuximab was efficacious and safe as first-line treatment in advanced nonsquamous non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: In this single-arm, multicenter clinical trial, patients with Stage IIIB/IV nonsquamous NSCLC received first-line therapy consisting of pemetrexed (500 mg/m(2)) and cisplatin (75 mg/m(2)) on Day 1 (21-day cycles) plus weekly cetuximab (400 mg/m(2) loading dose, then 250 mg/m(2)) for 4-6 cycles. Non-progressing patients received maintenance therapy consisting of pemetrexed and cetuximab as above until disease progression. All patients received vitamin supplementation, dexamethasone, and antihistamine prophylaxis. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), 1-year survival rate, translational research (TR) and safety. RESULTS: Of the 113 patients receiving study drug, 109 were protocol-qualified. All patients completed >/=1 cycle of induction, and 51 (45%) and 49 (43%) patients completed >/=1 cycle of maintenance with pemetrexed and cetuximab, respectively. The ORR (n = 109) was 38.5% (80% confidence interval [CI], 32.3-45.1%), all partial responses. Median PFS was 5.8 (80% CI, 4.4-6.7) months. One-year survival rate was 45% (80% CI, 39-51%). In exploratory analyses, there was some preliminary evidence of potential prognostic relationships with efficacy outcomes for epidermal growth factor receptor and thyroid transcription factor-1 protein expression, but not for KRAS mutation or for thymidylate synthase or folate receptor-alpha protein expression. Seventy-three (64.6%) patients had study drug-related Grade 3/4 adverse events (AEs). Drug-related serious AEs were reported in 31 (27.4%) patients. There were 3 (2.7%) potentially drug-related deaths on-study or within 30 days of follow up. CONCLUSION: Pemetrexed, cisplatin, and cetuximab appeared efficacious and tolerable in advanced nonsquamous NSCLC patients. The TR outcomes are hypothesis-generating given the study's size and nonrandomized nature. CI - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved. FAU - Schmid-Bindert, Gerald AU - Schmid-Bindert G AD - University Medical Center Mannheim of Heidelberg University, Mannheim, Germany. Electronic address: gerald.schmid-bindert@medma.uni-heidelberg.de. FAU - Gebbia, Vittorio AU - Gebbia V AD - La Maddalena Clinic for Cancer, University of Palermo, Palermo, Italy. FAU - Mayer, Frank AU - Mayer F AD - Medizinische Universitaetsklinik und Poliklinik, Tuebingen, Germany. FAU - Arriola, Edurne AU - Arriola E AD - Hospital del Mar, Barcelona, Spain. FAU - Marquez-Medina, Diego AU - Marquez-Medina D AD - Hospital Universitari Arnau de Vilanova, Lleida, Spain. FAU - Syrigos, Kostas AU - Syrigos K AD - Athens School of Medicine, Athens, Greece. FAU - Biesma, Bonne AU - Biesma B AD - Jeroen Bosch Ziekenhuis, 's-Hertogenbosch, The Netherlands. FAU - Leschinger, Monika Iris AU - Leschinger MI AD - Lilly Deutschland GmbH, Bad Homburg, Germany. FAU - Frimodt-Moller, Bente AU - Frimodt-Moller B AD - Eli Lilly and Company, Copenhagen, Denmark. FAU - Ripoche, Veronique AU - Ripoche V AD - Eli Lilly France, Suresnes, France. FAU - Myrand, Scott P AU - Myrand SP AD - Eli Lilly and Company, Indianapolis, USA. FAU - Nguyen, Tuan S AU - Nguyen TS AD - Eli Lilly and Company, Indianapolis, USA. FAU - Hozak, Rebecca R AU - Hozak RR AD - Eli Lilly and Company, Indianapolis, USA. FAU - Zimmermann, Annamaria AU - Zimmermann A AD - Eli Lilly and Company, Indianapolis, USA. FAU - Visseren-Grul, Carla AU - Visseren-Grul C AD - Eli Lilly Oncology, Houten, The Netherlands. FAU - Schuette, Wolfgang AU - Schuette W AD - Krankenhaus Martha-Maria Halle-Doelau, Halle, Germany. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20130620 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Glutamates) RN - 04Q9AIZ7NO (Pemetrexed) RN - 5Z93L87A1R (Guanine) RN - PQX0D8J21J (Cetuximab) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Adult MH - Aged MH - Antibodies, Monoclonal, Humanized/administration & dosage MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality/*pathology MH - Cetuximab MH - Cisplatin/administration & dosage MH - Female MH - Glutamates/administration & dosage MH - Guanine/administration & dosage/analogs & derivatives MH - Humans MH - Induction Chemotherapy MH - Lung Neoplasms/*drug therapy/mortality/*pathology MH - Maintenance Chemotherapy MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Pemetrexed MH - Translational Research, Biomedical MH - Treatment Outcome OTO - NOTNLM OT - Cetuximab OT - Cisplatin OT - Epidermal growth factor receptor OT - Folate receptor-alpha OT - NSCLC OT - Pemetrexed OT - Thymidylate synthase OT - Thyroid transcription factor EDAT- 2013/06/25 06:00 MHDA- 2014/04/09 06:00 CRDT- 2013/06/25 06:00 PHST- 2013/02/12 00:00 [received] PHST- 2013/05/13 00:00 [revised] PHST- 2013/05/18 00:00 [accepted] PHST- 2013/06/25 06:00 [entrez] PHST- 2013/06/25 06:00 [pubmed] PHST- 2014/04/09 06:00 [medline] AID - S0169-5002(13)00222-5 [pii] AID - 10.1016/j.lungcan.2013.05.010 [doi] PST - ppublish SO - Lung Cancer. 2013 Sep;81(3):428-434. doi: 10.1016/j.lungcan.2013.05.010. Epub 2013 Jun 20.