Gemcitabine plus erlotinib followed by capecitabine versus capecitabine plus erlotinib followed by gemcitabine in advanced pancreatic cancer: final results of a randomised phase 3 trial of the 'Arbeitsgemeinschaft Internistische Onkologie' (AIO-PK0104).
Gemcitabine plus erlotinib followed by capecitabine versus capecitabine plus erlotinib followed by gemcitabine in advanced pancreatic cancer: final results of a randomised phase 3 trial of the 'Arbeitsgemeinschaft Internistische Onkologie' (AIO-PK0104).
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DOI：
10.1136/gutjnl-2012-302759
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发表时间：
2013-05
期刊：
影响因子：
24.5
通讯作者：
Boeck S
中科院分区：
文献类型：
--
作者：
Heinemann V;Vehling-Kaiser U;Waldschmidt D;Kettner E;Märten A;Winkelmann C;Klein S;Kojouharoff G;Gauler TC;von Weikersthal LF;Clemens MR;Geissler M;Greten TF;Hegewisch-Becker S;Rubanov O;Baake G;Höhler T;Ko YD;Jung A;Neugebauer S;Boeck S
AIO-PK 0104研究了晚期胰腺癌（PC）的两种治疗策略：比较了吉西他滨/厄洛替尼的参考序列和卡培他滨二线治疗与卡培他滨/厄洛替尼的反向实验序列。281例PC患者被随机分配至吉西他滨+厄洛替尼或卡培他滨+厄洛替尼一线治疗组。在治疗失败的情况下（例如，疾病进展或毒性），将患者分配至使用对照细胞生长抑制药物（不含厄洛替尼）的二线治疗。主要研究终点为一线和二线治疗后至治疗失败的时间（TTF）（TTF 2;非劣效性设计）。在173例随机化患者的存档肿瘤组织中分析了KRAS外显子2突变。在274例合格患者中，43例为局部晚期，231例为转移性疾病; 140例（51%）接受二线化疗。两组的中位TTF 2估计值均为4.2个月;吉西他滨/厄洛替尼继以卡培他滨治疗的中位总生存期为6.2个月，卡培他滨/厄洛替尼继以吉西他滨治疗的中位总生存期为6.9个月（HR 1.02，p=0.90）。与卡培他滨/厄洛替尼相比，吉西他滨/厄洛替尼一线治疗的TTF（TTF 1）显著延长（3.2 vs 2.2个月; HR 0.69，p=0.0034）。皮疹与TTF 2（皮疹等级0/1/2-4：2.9/4.3/ 6.7个月，p<0.0001）和生存期（3.4/7.0/ 9.6个月，p<0.0001）相关。在一线和二线治疗期间，每组均显示出安全且可管理的毒性特征。KRAS野生型状态（52/173例患者，30%）与总生存期改善相关（HR 1.68，p=0.005）。两种治疗策略都是可行的，并证明了相当的疗效; KRAS可作为厄洛替尼治疗晚期PC患者的生物标志物。
AIO-PK0104 investigated two treatment strategies in advanced pancreatic cancer (PC): a reference sequence of gemcitabine/erlotinib followed by 2nd-line capecitabine was compared with a reverse experimental sequence of capecitabine/erlotinib followed by gemcitabine. 281 patients with PC were randomly assigned to 1st-line treatment with either gemcitabine plus erlotinib or capecitabine plus erlotinib. In case of treatment failure (eg, disease progression or toxicity), patients were allocated to 2nd-line treatment with the comparator cytostatic drug without erlotinib. The primary study endpoint was time to treatment failure (TTF) after 1st- and 2nd-line therapy (TTF2; non-inferiority design). KRAS exon 2 mutations were analysed in archival tumour tissue from 173 of the randomised patients. Of the 274 eligible patients, 43 had locally advanced and 231 had metastatic disease; 140 (51%) received 2nd-line chemotherapy. Median TTF2 was estimated with 4.2 months in both arms; median overall survival was 6.2 months with gemcitabine/erlotinib followed by capecitabine and 6.9 months with capecitabine/erlotinib followed by gemcitabine, respectively (HR 1.02, p=0.90). TTF for 1st-line therapy (TTF1) was significantly prolonged with gemcitabine/ erlotinib compared to capecitabine/erlotinib (3.2 vs 2.2 months; HR 0.69, p=0.0034). Skin rash was associated with both TTF2 (rash grade 0/1/2–4:2.9/4.3/ 6.7 months, p<0.0001) and survival (3.4/7.0/ 9.6 months, p<0.0001). Each arm showed a safe and manageable toxicity profile during 1st- and 2nd-line therapy. A KRAS wild-type status (52/173 patients, 30%) was associated with an improved overall survival (HR 1.68, p=0.005). Both treatment strategies are feasible and demonstrated comparable efficacy; KRAS may serve as biomarker in patients with advanced PC treated with erlotinib.
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影响因子：
24.5
作者：
Dahan L;Bonnetain F;Ychou M;Mitry E;Gasmi M;Raoul JL;Cattan S;Phelip JM;Hammel P;Chauffert B;Michel P;Legoux JL;Rougier P;Bedenne L;Seitz JF;Fédération Francophone de Cancérologie Digestive
通讯作者：
Fédération Francophone de Cancérologie Digestive
影响因子：
3.5
作者：
Boeck, Stefan;Wilkowski, Ralf;Heinemann, Volker
通讯作者：
Heinemann, Volker
影响因子：
50.5
作者：
Boeck, S.;Hoehler, T.;Heinemann, V.
通讯作者：
Heinemann, V.
影响因子：
45.3
作者：
Moore, Malcolm J.;Goldstein, David;Parulekar, Wendy
通讯作者：
Parulekar, Wendy
影响因子：
45.3
作者：
Cunningham, David;Chau, Ian;Neoptolemos, John P.
通讯作者：
Neoptolemos, John P.