Page 35 - รายงานประจำปี ๒๕๕๘ ศูนย์องค์รวมเพื่อการศึกษาและบำบัดโรคมะเร็ง คณะแพทยศาสตร์

35

บทความตีพิมพ์ข้อมูลของผู้ป่วยซึ่งทางศูนย์ฯ

ได้ร่วมในการทำาวิจัย SQUIRE

THE LANCET ONCOLOGY

Articles

Necitumumab plus gemcitabine and cisplatin versus
gemcitabine and cisplatin alone as first-line therapy in

patients with stage IV squamous non-small-cell lung cancer
(SQUIRE): an open-label, randomised, controlled phase 3 trial

Nick Thatcher, Fred R Hirsch, Alexander V Luft, Aleksandra Szczesna, Tudor E Ciuleanu, Mircea Dediu, Rodryg Ramlau, Rinat K Galiulin,
Beatrix Bálint, György Losonczy, Andrzej Kazarnowicz, Keunchil Park, Christian Schumann, Martin Reck, Henrik Depenbrock, Shivani Nanda,
Anamarija Kruljac-Letunic, Raffael Kurek, Luis Paz-Ares, Mark A Socinski, for the SQUIRE investigators*

Summary
Background Necitumumab is a second-generation, recombinant, human immunoglobulin G1 EGFR antibody. In this Lancet Oncol 2015; 16: 763–74
study, we aimed to compare treatment with necitumumab plus gemcitabine and cisplatin versus gemcitabine and Published Online
cisplatin alone in patients with previously untreated stage IV squamous non-small-cell lung cancer. June 2, 2015
http://dx.doi.org/10.1016/
S1470-2045(15)00021-2
Methods We did this open-label, randomised phase 3 study at 184 investigative sites in 26 countries. Patients aged 18 years
or older with histologically or cytologically confirmed stage IV squamous non-small-cell lung cancer, with an Eastern See Comment page 738

Cooperative Oncology Group (ECOG) performance status of 0–2 and adequate organ function and who had not received *The SQUIRE investigators are
listed in the appendix
previous chemotherapy for their disease were eligible for inclusion. Enrolled patients were randomly assigned centrally The Christie Hospital,
1:1 to a maximum of six 3-week cycles of gemcitabine and cisplastin chemotherapy with or without necitumumab Manchester, UK
according to a block randomisation scheme (block size of four) by a telephone-based interactive voice response system or (Prof N Thatcher FRCP);
interactive web response system. Chemotherapy was gemcitabine 1250 mg/m² administered intravenously over 30 min University of Colorado Cancer
on days 1 and 8 of a 3-week cycle and cisplatin 75 mg/m² administered intravenously over 120 min on day 1 of a 3-week Center, Aurora, CO, USA
(Prof F R Hirsch MD); Leningrad
cycle. Necitumumab 800 mg, administered intravenously over a minimum of 50 min on days 1 and 8, was continued Regional Clinical Hospital,

after the end of chemotherapy until disease progression or intolerable toxic side-effects occurred. Randomisation was St Petersburg, Russia

stratified by ECOG performance status and geographical region. Neither physicians nor patients were masked to group (A V Luft MD); Regional Lung

assignment because of the expected occurrence of acne-like rash—a class effect of EGFR antibodies—that would have Disease Hospital, Otwock,
Poland (A Szczesna MD);
unmasked most patients and investigators to treatment. The primary endpoint was overall survival, analysed by intention Institutul Oncologic

to treat. We report the final clinical analysis. This study is registered with ClinicalTrials.gov, number NCT00981058. Prof Dr Ion Chiricuta and UMF
Iuliu Hatieganu, Cluj-Napoca,
Findings Between Jan 7, 2010, and Feb 22, 2012, we enrolled 1093 patients and randomly assigned them to receive Romania (Prof T E Ciuleanu MD);
Institute of Oncology,
necitumumab plus gemcitabine and cisplatin (n=545) or gemcitabine and cisplatin (n=548). Overall survival was Bucharest, Romania

significantly longer in the necitumumab plus gemcitabine and cisplatin group than in the gemcitabine and cisplatin (M Dediu MD); Poznan
alone group (median 11·5 months [95% CI 10·4–12·6]) vs 9·9 months [8·9–11·1]; stratified hazard ratio 0·84 [95% CI University of Medical Sciences,

0·74–0·96; p=0·01]). In the necitumumab plus gemcitabine and cisplatin group, the number of patients with at least Poznań, Poland
(Prof R Ramlau MD); Omsk
one grade 3 or worse adverse event was higher (388 [72%] of 538 patients) than in the gemcitabine and cisplatin group Regional Oncology Center,
(333 [62%] of 541), as was the incidence of serious adverse events (257 [48%] of 538 patients vs 203 [38%] of 541). More Omsk, Russia (R K Galiulin MD);
patients in the necitumumab plus gemcitabine and cisplatin group had grade 3–4 hypomagnesaemia (47 [9%] of Csongrád County Hospital of
Chest Diseases, Deszk, Hungary
538 patients in the necitumumab plus gemcitabine and cisplatin group vs six [1%] of 541 in the gemcitabine and (B Bálint MD); Semmelweis
cisplatin group) and grade 3 rash (20 [4%] vs one [<1%]). Including events related to disease progression, adverse events University Department of
with an outcome of death were reported for 66 (12%) of 538 patients in the necitumumab plus gemcitabine and cisplatin Pulmonology, Budapest,
group and 57 (11%) of 541 patients in the gemcitabine and cisplatin group; these were deemed to be related to study Hungary (Prof G Losonczy MD);
Tuberculosis and Lung Disease
drugs in 15 (3%) and ten (2%) patients, respectively. Overall, we found that the safety profile of necitumumab plus Hospital, Olsztyn, Poland

gemcitabine and cisplatin was acceptable and in line with expectations. (A Kazarnowicz MD); Samsung
Medical Center, Seoul, South

Interpretation Our findings show that the addition of necitumumab to gemcitabine and cisplatin chemotherapy Korea (K Park MD); Department
of Internal Medicine II,
improves overall survival in patients with advanced squamous non-small-cell lung cancer and represents a new first- University Hospital of Ulm,

line treatment option for this disease. Ulm, Germany
(Prof C Schumann MD); Clinic
Funding Eli Lilly and Company. for Pneumology, Thoracic
Oncology, Sleep- and
Respiratory Critical Care,
Introduction squamous and non-squamous non-small-cell lung Kempten-Oberallgaeu
Squamous cell carcinomas account for 30% of non- cancers are distinctive, with both of these aspects Hospitals, Kempten, Germany
small-cell lung cancers worldwide. In addition to potentially affecting treatment selection. For patients (Prof C Schumann); Lung Clinic
1

2
Grosshansdorf, Airway
histopathological differences, the mutational profiles of with squamous non-small-cell lung cancer, although

www.thelancet.com/oncology Vol 16 July 2015 763