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Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials.

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成果类型:
期刊论文
作者:
Yang, James Chih-Hsin*;Wu, Yi-Long;Schuler, Martin;Sebastian, Martin;Popat, Sanjay;Yamamoto, Nobuyuki;Zhou, Caicun;Hu, Cheng-Ping;O'Byrne, Kenneth;Feng, Jifeng;Lu, Shun;Huang, Yunchao;Geater, Sarayut L;Lee, Kye Young;Tsai, Chun-Ming;Gorbunova, Vera;Hirsh, Vera;Bennouna, Jaafar;Orlov, Sergey;Mok, Tony;Boyer, Michael;Su, Wu-Chou;Lee, Ki Hyeong;Kato, Terufumi;Massey, Dan;Shahidi, Mehdi;Zazulina, Victoria;Sequist, Lecia V
通讯作者:
Yang, James Chih-Hsin
作者机构:
[Popat, Sanjay] Royal Marsden Hosp, London SW3 6JJ, England.
[Feng, Jifeng] Jiangsu Prov Canc Hosp, Nanjing, Jiangsu, Peoples R China.
[Gorbunova, Vera] Russian Acad Med Sci, FSBI N N Blokhin Russian Canc Res Ctr, Moscow, Russia.
[Massey, Dan; Zazulina, Victoria; Shahidi, Mehdi] Boehringer Ingelheim Ltd UK, Bracknell, Berks, England.
[Su, Wu-Chou] Natl Cheng Kung Univ Hosp, Tainan 70428, Taiwan.
通讯机构:
[Yang, JCH] Natl Taiwan Univ Hosp, Taipei 100, Taiwan.
语种:
英文
期刊:
The Lancet. Oncology
ISSN:
1470-2045
年:
2015
卷:
16
期:
2
页码:
141-151
文献类别:
WOS:Article
所属学科:
ESI学科类别:临床医学;WOS学科类别:Oncology
入藏号:
WOS:000348841700030;PMID:25589191
基金类别:
Boehringer Ingelheim
机构署名:
本校为其他机构
院系归属:
临床肿瘤学院
摘要:
BACKGROUND: We aimed to assess the effect of afatinib on overall survival of patients with EGFR mutation-positive lung adenocarcinoma through an analysis of data from two open-label, randomised, phase 3 trials. METHODS: Previously untreated patients with EGFR mutation-positive stage IIIB or IV lung adenocarcinoma were enrolled in LUX-Lung 3 (n=345) and LUX-Lung 6 (n=364). These patients were randomly assigned in a 2:1 ratio to receive afatinib or chemotherapy (pemetrexed-cisplatin [LUX-Lung 3] or gemcitabine-cisplatin [LUX-Lung 6]), stratified by EGFR mutation (exon 19 deletion [del19], Leu858Arg, or other) and ethnic origin (LUX-Lung 3 only). We planned analyses of mature overall survival data in the intention-to-treat population after 209 (LUX-Lung 3) and 237 (LUX-Lung 6) deaths. These ongoing studies are registered with ClinicalTrials.gov, numbers NCT00949650 and NCT01121393. FINDINGS: Median follow-up in LUX-Lung 3 was 41 months (IQR 35-44); 213 (62%) of 345 patients had died. Median follow-up in LUX-Lung 6 was 33 months (IQR 31-37); 246 (68%) of 364 patients had died. In LUX-Lung 3, median overall survival was 28.2 months (95% CI 24.6-33.6) in the afatinib group and 28.2 months (20.7-33.2) in the pemetrexed-cisplatin group (HR 0.88, 95% CI 0.66-1.17, p=0.39). In LUX-Lung 6, median overall survival was 23.1 months (95% CI 20.4-27.3) in the afatinib group and 23.5 months (18.0-25.6) in the gemcitabine-cisplatin group (HR 0.93, 95% CI 0.72-1.22, p=0.61). However, in preplanned analyses, overall survival was significantly longer for patients with del19-positive tumours in the afatinib group than in the chemotherapy group in both trials: in LUX-Lung 3, median overall survival was 33.3 months (95% CI 26.8-41.5) in the afatinib group versus 21.1 months (16.3-30.7) in the chemotherapy group (HR 0.54, 95% CI 0.36-0.79, p=0.0015); in LUX-Lung 6, it was 31.4 months (95% CI 24.2-35.3) versus 18.4 months (14.6-25.6), respectively (HR 0.64, 95% CI 0.44-0.94, p=0.023). By contrast, there were no significant differences by treatment group for patients with EGFR Leu858Arg-positive tumours in either trial: in LUX-Lung 3, median overall survival was 27.6 months (19.8-41.7) in the afatinib group versus 40.3 months (24.3-not estimable) in the chemotherapy group (HR 1.30, 95% CI 0.80-2.11, p=0.29); in LUX-Lung 6, it was 19.6 months (95% CI 17.0-22.1) versus 24.3 months (19.0-27.0), respectively (HR 1.22, 95% CI 0.81-1.83, p=0.34). In both trials, the most common afatinib-related grade 3-4 adverse events were rash or acne (37 [16%] of 229 patients in LUX-Lung 3 and 35 [15%] of 239 patients in LUX-Lung 6), diarrhoea (33 [14%] and 13 [5%]), paronychia (26 [11%] in LUX-Lung 3 only), and stomatitis or mucositis (13 [5%] in LUX-Lung 6 only). In LUX-Lung 3, neutropenia (20 [18%] of 111 patients), fatigue (14 [13%]) and leucopenia (nine [8%]) were the most common chemotherapy-related grade 3-4 adverse events, while in LUX-Lung 6, the most common chemotherapy-related grade 3-4 adverse events were neutropenia (30 [27%] of 113 patients), vomiting (22 [19%]), and leucopenia (17 [15%]). INTERPRETATION: Although afatinib did not improve overall survival in the whole population of either trial, overall survival was improved with the drug for patients with del19 EGFR mutations. The absence of an effect in patients with Leu858Arg EGFR mutations suggests that EGFR del19-positive disease might be distinct from Leu858Arg-positive disease and that these subgroups should be analysed separately in future trials. FUNDING: Boehringer Ingelheim.
参考文献:
Riely GJ, 2006, CLIN CANCER RES, V12, P839, DOI 10.1158/1078-0432.CCR-05-1846
Okabe T, 2007, CANCER RES, V67, P2046, DOI 10.1158/0008-5472.CAN-06-3339
Jackman DM, 2006, CLIN CANCER RES, V12, P3908, DOI 10.1158/1078-0432.CCR-06-0462
Sequist LV, 2013, J CLIN ONCOL, V31, P3327, DOI 10.1200/JCO.2012.44.2806
Yang JCH, 2012, LANCET ONCOL, V13, P539, DOI 10.1016/S1470-2045(12)70086-4

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