Gefitinib versus placebo as maintenance therapy in
patients with locally advanced or metastatic non-small-cell lung cancer (INFORM;
C-TONG 0804): a multicentre, double-blind randomised phase 3 trial
The Lancet Oncology, Volume 13, Issue 5, Pages 466 - 475, May 2012
Prof Li Zhang MD a , Shenglin Ma MD b, Xiangqun Song MSc c, Baohui Han MD d, Ying Cheng MSc e, Cheng Huang MD f, Shujun Yang MD g, Xiaoqing Liu MD h, Yunpeng Liu MD i, Shun Lu MD j, Jie Wang MD k, Shucai Zhang MD l, Caicun Zhou MD m, Xiangwei Zhang MD n, Nobuya Hayashi BA o, Mengzhao Wang MD p, on behalf of the INFORM investigators‡
Background: Maintenance treatment of patients with advanced non-small-cell lung cancer (NSCLC) without disease progression after first-line chemotherapy is a subject of ongoing research. The aim of the randomised, double-blind, placebo-controlled, INFORM study was to investigate the efficacy, safety, and tolerability of the EGFR—tyrosine-kinase inhibitor gefitinib in the maintenance setting.
Methods: Patients were aged 18 years or older, were of east Asian ethnic origin, had a life expectancy of more than 12 weeks, histologically or cytologically confirmed stage IIIb or IV NSCLC, a WHO performance status of 0—2, and had completed four cycles of first-line platinum-based doublet chemotherapy without disease progression or unacceptable toxic effects. Between Sept 28, 2008 and Aug 11, 2009, 296 patients were randomly assigned 1:1 to receive either gefitinib (250 mg per day orally) or placebo (orally) within 3—6 weeks after chemotherapy until progression or unacceptable toxic effects. Randomisation was done via an interactive web response system with computer-generated randomisation codes. Our primary endpoint was progression-free survival assessed in the intention-to-treat population. This completed study is registered with Clinicaltrials.gov, number NCT00770588.
Findings: Progression-free survival was significantly longer with gefitinib (n=148) than with placebo (148) (median progression-free survival 4·8 months [95% CI 3·2—8·5] vs 2·6 months [1·6—2·8]; hazard ratio [HR] 0·42, 95% CI 0·33—0·55; p<0·0001). Adverse events occurred more frequently with gefitinib than with placebo; the most common adverse events of any grade were rash (73 [50%] of147
in the gefitinib group vs 14 [9%] of 148 in the placebo group), diarrhoea (37 [25%] vs 13 [9%]),
and alanine aminotransferase increase (31 [21%] vs 12 [8%]). The most commonly
reported grade 3 or 4 adverse event was alanine aminotransferase increase (3 [2%]
of 147 in the gefitinib
group, none of 148 in
the placebo group). Ten of 147 (7%) patients given gefitinib and five of 148 (3%)
patients given placebo had serious adverse events. Three deaths were thought to
be related to treatment with gefitinib: one from interstitial lung disease; one
from lung infection; and one from pneumonia.
Interpretation: Maintenance treatment with gefitinib significantly prolonged progression-free survival compared with placebo in patients from east Asia with advanced NSCLC who achieved disease control after first-line chemotherapy. Clinicians should consider these data when making decisions about maintenance treatment in such patients.
Funding: AstraZeneca.
肺癌治疗“空窗期”靶向药物可有作为 2012/5/24药品资讯网信息中心 中山大学肿瘤防治中心张力教授课题组完成的一项国内多中心研究表明，对于晚期肺癌患者一线治疗后的"空窗期"，临床医生不能无所作为，应采用靶向药物继续维持治疗，以控制肿瘤生长，而不能像以往那样，待肿瘤继续长大，再进行二线化疗。该研究成果近日发表在国际权威杂志《柳叶刀•肿瘤》上。 晚期非小细胞肺癌的治疗策略通常是消极的。张力介绍，许多肺癌患者在完成第一阶段化疗（通常4个～6个疗程）后，可以取得肿瘤缩小或者控制的效果。许多临床医生很无奈地告诉患者要等待，直到发现肿瘤继续生长，再进行第二阶段化疗，周而复始。一般来说，五成患者在停止治疗后2个多月，就要继续用化疗控制肿瘤生长。而研究表明，肺癌患者再次化疗，患者生存质量会下降，死亡风险也更高。2008年，张力牵头在全球首次采用靶向药物吉非替尼开展了前瞻性、随机对照的晚期肺癌维持治疗的三期临床研究（INFORM研究）。该研究于2009年完成入组，并随访2年。研究人员将296名常规一线化疗后肿瘤获得缓解的晚期非小细胞肺癌患者，随机分为吉非替尼维持治疗和安慰剂观察对照组。研究结果显示，相比对照组，治疗组患者肿瘤无进展生存期明显延长，为4.8个月，而对照组为2.6个月，疾病进展风险下降了58%。由于三成的中国非小细胞肺癌患者具有肿瘤表皮生长因子EGFR基因突变，研究人员回顾性分析了治疗组EGFR基因突变患者治疗效果，发现治疗组生存期为16.6个月，远高于安慰剂组的2.7个月。 张力指出，吉非替尼治疗组的有效率和患者生活质量改善均显著优于安慰剂组，利用靶向药物继续进行治疗，可以控制患者肿瘤生长，能取得更好的治疗效果。2011年6月，在第47届美国临床肿瘤学会年会上，张力首次发布这一研究结果。 INFORM研究是中国研究者在肺癌领域自主设计、独立开展的随机、双盲三期临床研究，也是到目前为止在肺癌领域我国第一个入选ASCO大会发言的临床研究。该研究参与单位分属16个省（区、市），其中包括北京大学肿瘤医院、上海交通大学附属胸科医院、浙江省肿瘤医院、河南省肿瘤医院、广西医科大学附属肿瘤医院等27家医疗机构。
The Lancet Oncology, Volume 13, Issue 5, Pages 466 - 475, May 2012
Prof Li Zhang MD a , Shenglin Ma MD b, Xiangqun Song MSc c, Baohui Han MD d, Ying Cheng MSc e, Cheng Huang MD f, Shujun Yang MD g, Xiaoqing Liu MD h, Yunpeng Liu MD i, Shun Lu MD j, Jie Wang MD k, Shucai Zhang MD l, Caicun Zhou MD m, Xiangwei Zhang MD n, Nobuya Hayashi BA o, Mengzhao Wang MD p, on behalf of the INFORM investigators‡
Background: Maintenance treatment of patients with advanced non-small-cell lung cancer (NSCLC) without disease progression after first-line chemotherapy is a subject of ongoing research. The aim of the randomised, double-blind, placebo-controlled, INFORM study was to investigate the efficacy, safety, and tolerability of the EGFR—tyrosine-kinase inhibitor gefitinib in the maintenance setting.
Methods: Patients were aged 18 years or older, were of east Asian ethnic origin, had a life expectancy of more than 12 weeks, histologically or cytologically confirmed stage IIIb or IV NSCLC, a WHO performance status of 0—2, and had completed four cycles of first-line platinum-based doublet chemotherapy without disease progression or unacceptable toxic effects. Between Sept 28, 2008 and Aug 11, 2009, 296 patients were randomly assigned 1:1 to receive either gefitinib (250 mg per day orally) or placebo (orally) within 3—6 weeks after chemotherapy until progression or unacceptable toxic effects. Randomisation was done via an interactive web response system with computer-generated randomisation codes. Our primary endpoint was progression-free survival assessed in the intention-to-treat population. This completed study is registered with Clinicaltrials.gov, number NCT00770588.
Findings: Progression-free survival was significantly longer with gefitinib (n=148) than with placebo (148) (median progression-free survival 4·8 months [95% CI 3·2—8·5] vs 2·6 months [1·6—2·8]; hazard ratio [HR] 0·42, 95% CI 0·33—0·55; p<0·0001). Adverse events occurred more frequently with gefitinib than with placebo; the most common adverse events of any grade were rash (73 [50%] of
Interpretation: Maintenance treatment with gefitinib significantly prolonged progression-free survival compared with placebo in patients from east Asia with advanced NSCLC who achieved disease control after first-line chemotherapy. Clinicians should consider these data when making decisions about maintenance treatment in such patients.
Funding: AstraZeneca.
肺癌治疗“空窗期”靶向药物可有作为 2012/5/24药品资讯网信息中心 中山大学肿瘤防治中心张力教授课题组完成的一项国内多中心研究表明，对于晚期肺癌患者一线治疗后的"空窗期"，临床医生不能无所作为，应采用靶向药物继续维持治疗，以控制肿瘤生长，而不能像以往那样，待肿瘤继续长大，再进行二线化疗。该研究成果近日发表在国际权威杂志《柳叶刀•肿瘤》上。 晚期非小细胞肺癌的治疗策略通常是消极的。张力介绍，许多肺癌患者在完成第一阶段化疗（通常4个～6个疗程）后，可以取得肿瘤缩小或者控制的效果。许多临床医生很无奈地告诉患者要等待，直到发现肿瘤继续生长，再进行第二阶段化疗，周而复始。一般来说，五成患者在停止治疗后2个多月，就要继续用化疗控制肿瘤生长。而研究表明，肺癌患者再次化疗，患者生存质量会下降，死亡风险也更高。2008年，张力牵头在全球首次采用靶向药物吉非替尼开展了前瞻性、随机对照的晚期肺癌维持治疗的三期临床研究（INFORM研究）。该研究于2009年完成入组，并随访2年。研究人员将296名常规一线化疗后肿瘤获得缓解的晚期非小细胞肺癌患者，随机分为吉非替尼维持治疗和安慰剂观察对照组。研究结果显示，相比对照组，治疗组患者肿瘤无进展生存期明显延长，为4.8个月，而对照组为2.6个月，疾病进展风险下降了58%。由于三成的中国非小细胞肺癌患者具有肿瘤表皮生长因子EGFR基因突变，研究人员回顾性分析了治疗组EGFR基因突变患者治疗效果，发现治疗组生存期为16.6个月，远高于安慰剂组的2.7个月。 张力指出，吉非替尼治疗组的有效率和患者生活质量改善均显著优于安慰剂组，利用靶向药物继续进行治疗，可以控制患者肿瘤生长，能取得更好的治疗效果。2011年6月，在第47届美国临床肿瘤学会年会上，张力首次发布这一研究结果。 INFORM研究是中国研究者在肺癌领域自主设计、独立开展的随机、双盲三期临床研究，也是到目前为止在肺癌领域我国第一个入选ASCO大会发言的临床研究。该研究参与单位分属16个省（区、市），其中包括北京大学肿瘤医院、上海交通大学附属胸科医院、浙江省肿瘤医院、河南省肿瘤医院、广西医科大学附属肿瘤医院等27家医疗机构。
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