Brigatinib Versus Crizotinib in ALK Inhibitor-Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial

被引：261

作者：

Camidge, D. Ross ^{[1
]}

Kim, Hye Ryun ^{[2
]}

Ahn, Myung-Ju ^{[3
]}

Yang, James C. H. ^{[4
]}

Han, Ji-Youn ^{[5
]}

Hochmair, Maximilian J. ^{[6
]}

Lee, Ki Hyeong ^{[7
]}

Delmonte, Angelo ^{[8
]}

Campelo, Maria Rosario Garcia ^{[9
]}

Kim, Dong-Wan ^{[10
]}

Griesinger, Frank ^{[11
]}

Felip, Enriqueta ^{[12
]}

Califano, Raffaele ^{[13
,14
]}

Spira, Alexander I. ^{[15
]}

Gettinger, Scott N. ^{[16
]}

Tiseo, Marcello ^{[17
]}

Lin, Huamao M. ^{[18
]}

Liu, Yuyin ^{[19
]}

Vranceanu, Florin ^{[20
]}

Niu, Huifeng ^{[21
]}

Zhang, Pingkuan ^{[22
]}

Popat, Sanjay ^{[23
]}

机构：

[1] Univ Colorado, Ctr Canc, Dept Med, 1665 Aurora Court, Aurora, CO 80045 USA

[2] Yonsei Univ, Coll Med, Yonsei Canc Ctr, Dept Internal Med,Div Med Oncol, Seoul, South Korea

[3] Samsung Med Ctr, Div Hematol Oncol, Seoul, South Korea

[4] Natl Taiwan Univ, Canc Ctr, Dept Med Oncol, Taipei, Taiwan

[5] Natl Canc Ctr, Dept Precis Med, Gyeonggi, South Korea

[6] Karl Landsteiner Inst Lung Res & Pulm Oncol, Dept Resp & Crit Care Med, Vienna, Austria

[7] Chungbuk Natl Univ Hosp, Internal Med Dept, Chungbuk, South Korea

[8] Ist Ricovero & Cura Carattere Sci IRCCS, Ist Romagnolo Studio Tumori Dino Amadori IRST, Dept Med Oncol, Meldola, Italy

[9] Univ Hosp A Coruna, Complejo Hosp Univ A Coruna CHUAC, Dept Med Oncol, La Coruna, Spain

[10] Seoul Natl Univ, Coll Med, Seoul Natl Univ Hosp, Dept Internal Med, Seoul, South Korea

[11] Carl von Ossietzky Univ Oldenburg, Pius Hosp Oldenburg, Dept Hematol & Oncol, Oldenburg, Germany

[12] Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, Barcelona, Spain

[13] Christie NHS Fdn Trust, Dept Med Oncol, Manchester, Lancs, England

[14] Univ Manchester, Dept Med Oncol, Div Canc Sci, Manchester, Lancs, England

[15] US Oncol Res, Virginia Canc Specialists, Dept Med Oncol, Fairfax, VA USA

[16] Yale Canc Ctr, Dept Med Oncol, New Haven, CT USA

[17] Univ Hosp Parma, Dept Med & Surg, Parma, Italy

[18] Wholly Owned Subsidiary Takeda Pharmaceut Co Ltd, Global Evidence & Outcome Millennium Pharmaceut, Cambridge, MA USA

[19] Wholly Owned Subsidiary Takeda Pharmaceut Co Ltd, Oncol Stat Millennium Pharmaceut Inc, Cambridge, MA USA

[20] Wholly Owned Subsidiary Takeda Pharmaceut Co Ltd, Clin Sci Millennium Pharmaceut Inc, Cambridge, MA USA

[21] Wholly Owned Subsidiary Takeda Pharmaceut Co Ltd, Oncol Translat Sci Millennium Pharmaceut Inc, Cambridge, MA USA

[22] Wholly Owned Subsidiary Takeda Pharmaceut Co Ltd, Oncol Clin Res Millennium Pharmaceut Inc, Cambridge, MA USA

[23] Royal Marsden Hosp, London, England

来源：

JOURNAL OF THORACIC ONCOLOGY | 2021年 / 16卷 / 12期

关键词：

Anaplastic lymphoma kinase; ALK tyrosine kinase inhibitor; Brigatinib; Crizotinib; Non-small cell lung cancer; EML4-ALK FUSION GENE; LUNG; MUTATIONS; QLQ-C30; EGFR;

D O I：

10.1016/j.jtho.2021.07.035

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Introduction: In the phase 3 study entitled ALK in Lung cancer Trial of brigAtinib in 1st Line (ALTA-1L), which is a study of brigatinib in ALK inhibitor-naive advanced ALKpositive NSCLC, brigatinib exhibited superior progression free survival (PFS) versus crizotinib in the two planned interim analyses. Here, we report the final efficacy, safety, and exploratory results. Methods: Patients were randomized to brigatinib 180 mg once daily (7-d lead-in at 90 mg once daily) or crizotinib 250 mg twice daily. The primary end point was a blinded independent review committee-assessed PFS. Genetic alterations in plasma cell-free DNA were assessed in relation to clinical efficacy. Results: A total of 275 patients were enrolled (brigatinib, n = 137; crizotinib, n = 138). At study end, (brigatinib median follow-up = 40.4 mo), the 3-year PFS by blinded independent review committee was 43% (brigatinib) versus 19% (crizotinib; median = 24.0 versus 11.1 mo, hazard ratio [HR] = 0.48, 95% confidence interval [CI]: 0.35-0.66). The median overall survival was not reached in either group (HR = 0.81, 95% CI: 0.53-1.22). Posthoc analyses suggested an overall survival benefit for brigatinib in patients with baseline brain metastases (HR = 0.43, 95% CI: 0.21-0.89). Detectable baseline EML4-ALK fusion variant 3 and TP53 mutation in plasma were associated with poor PFS. Brigatinib exhibited superior efficacy compared with crizotinib regardless of EML4-ALK variant and TP53 mutation. Emerging secondary ALK mutations were rare in patients progressing on brigatinib. No new safety signals were observed. Conclusions: In the ALTA-1L final analysis, with longer follow-up, brigatinib continued to exhibit superior efficacy and tolerability versus crizotinib in patients with or without poor prognostic biomarkers. The suggested survival benefit with brigatinib in patients with brain metastases warrants future study. (c) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

引用

页码：2091 / 2108

页数：18

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