title: The Effect of Necitumumab in Combination with Gemcitabine plus Cisplatin on Tolerability and on Quality of Life: Results from the Phase 3 SQUIRE Trial.
abstract: Necitumumab, a second-generation, recombinant human immunoglobulin G1 epidermal growth factor receptor antibody in the phase 3 SQUIRE trial (NCT00981058), increased survival benefit for patients randomized to receive necitumumab plus gemcitabine-cisplatin compared with those who received gemcitabine-cisplatin. Here we characterize health-related quality of life (HRQoL) and tolerability results.
  
  
  
  A total of 1093 patients with stage IV squamous non-small cell lung cancer were randomized 1:1 to receive necitumumab (800 mg absolute dose intravenously [IV]) plus gemcitabine-cisplatin (gemcitabine = 1250 mg/m(2) IV on days 1 and 8; cisplatin = 75 mg/m(2) IV on day 1) or gemcitabine-cisplatin alone (every 21 days) for up to six cycles. Patients receiving necitumumab plus gemcitabine-cisplatin without disease progression continued necitumumab until progression. HRQoL was measured by Eastern Cooperative Oncology Group performance status, the Lung Cancer Symptom Scale (LCSS), and the European Quality of Life Five-Dimensions questionnaire. Efficacy and LCSS outcomes were analyzed using the baseline maximum severity score of the LCSS. Tolerability was measured in terms of exposure to the study treatment and adverse events. Hospitalization rates were collected.
  
  
  
  Most patients in both study arms similarly maintained Eastern Cooperative Oncology Group performance status and comparable LCSS and European Quality of Life Five-Dimensions questionnaire assessments. Patients with a higher baseline LCSS had a greater survival benefit on the necitumumab arm. Chemotherapy exposure was similar in both treatment arms; 51% of patients on the necitumumab plus gemcitabine-cisplatin arm continued on single-agent necitumumab. The most frequent grade 4 adverse events were neutropenia (6.1% versus 7.9%) and thrombocytopenia (3.2% versus 4.3%) in the necitumumab plus gemcitabine-cisplatin versus gemcitabine-cisplatin arms, respectively. Hospitalizations were slightly higher with necitumumab plus gemcitabine-cisplatin (36.4%) than with gemcitabine-cisplatin (34.0%).
  
  
  
  The addition of necitumumab to gemcitabine-cisplatin was well tolerated, did not negatively affect HRQoL or toxicity, and particularly benefited patients with more severe baseline symptoms or lower HRQoL.
authors.affiliation: Department of Thoracic Oncology, LungenClinic Grosshansdorf, Airway Research Center North, Grosshansdorf, Germany. Electronic address: dr.martin.reck@web.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Reck
authors.affiliation: Lung Cancer Section, Division of Hematology/Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.affiliation: Leningrad Regional Clinical Hospital, St. Petersburg, Russia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Luft
authors.affiliation: Mazowieckie Centrum Leczenia Chorób Pluc, Otwock, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Szczęsna
authors.affiliation: Institute of Oncology "Alexandru Trestioreanu," Bucharest, Romania.
authors.forename: Mircea
authors.initials: M
authors.lastname: Dediu
authors.affiliation: Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Rodryg
authors.initials: R
authors.lastname: Ramlau
authors.affiliation: Semmelweis University Department of Pulmonology, Budapest, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Losonczy
authors.affiliation: Centre Hospitalier Le Mans, Le Mans, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Molinier
authors.affiliation: Department of Internal Medicine II, University Hospital of Ulm, Ulm, Germany; Clinic for Pneumology, Thoracic Oncology, Sleep- and Respiratory Critical Care, Kempten-Oberallgaeu Hospitals, Kempten, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schumann
authors.affiliation: Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gralla
authors.affiliation: Rush University Medical Center, Chicago, Illinois.
authors.forename: Philip
authors.initials: P
authors.lastname: Bonomi
authors.affiliation: Eli Lilly and Company, Earl Wood, United Kingdom.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Brown
authors.affiliation: Eli Lilly and Company, Bad Homburg, Germany.
authors.forename: Victoria
authors.initials: V
authors.lastname: Soldatenkova
authors.affiliation: Eli Lilly and Company, Paris, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Chouaki
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Coleman
authors.initials: C
authors.lastname: Obasaju
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Patrick
authors.initials: P
authors.lastname: Peterson
authors.affiliation: The Christie Hospital, Manchester, United Kingdom.
authors.forename: Nick
authors.initials: N
authors.lastname: Thatcher
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011788:Quality of Life; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; C527969:necitumumab; D002945:Cisplatin; D000093542:Gemcitabine
keywords: EQ-5D; Health-related quality of life; Lung Cancer Symptom Scale; Necitumumab; Tolerability