Local Consolidative Therapy Vs. Maintenance Therapy or Observation for Patients With Oligometastatic Non-Small-Cell Lung Cancer: Long-Term Results of a Multi-Institutional, Phase II, Randomized Study

被引：975

作者：

Gomez, Daniel R. ^{[1
]}

Tang, Chad ^{[1
]}

Zhang, Jianjun ^{[1
]}

Blumenschein, George R., Jr. ^{[1
]}

Hernandez, Mike ^{[1
]}

Lee, J. Jack ^{[1
]}

Ye, Rong ^{[1
]}

Palma, David A. ^{[2
]}

Louie, Alexander, V ^{[2
]}

Camidge, D. Ross ^{[3
]}

Doebele, Robert C. ^{[3
]}

Skoulidis, Ferdinandos ^{[1
]}

Gaspar, Laurie E. ^{[3
]}

Welsh, James W. ^{[1
]}

Gibbons, Don L. ^{[1
]}

Karam, Jose A. ^{[1
]}

Kavanagh, Brian D. ^{[3
]}

Tsao, Anne S. ^{[1
]}

Sepesi, Boris ^{[1
]}

Swisher, Stephen G. ^{[1
]}

Heymach, John, V ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[2] London Hlth Sci Ctr, London, ON, Canada

[3] Univ Colorado, Sch Med, Aurora, CO USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2019年 / 37卷 / 18期

基金：

美国国家卫生研究院;

关键词：

MULTICENTER;

D O I：

10.1200/JCO.19.00201

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSE Our previously published findings reported that local consolidative therapy (LCT) with radiotherapy or surgery improved progression-free survival (PFS) and delayed new disease in patients with oligometastatic non-small-cell lung cancer (NSCLC) that did not progress after front-line systemic therapy. Herein, we present the longer-term overall survival (OS) results accompanied by additional secondary end points. PATIENTS AND METHODS This multicenter, randomized, phase II trial enrolled patients with stage IV NSCLC, three or fewer metastases, and no progression at 3 or more months after front-line systemic therapy. Patients were randomly assigned (1:1) to maintenance therapy or observation (MT/O) or to LCT to all active disease sites. The primary end point was PFS; secondary end points were OS, toxicity, and the appearance of new lesions. All analyses were two sided, and P values less than .10 were deemed significant. RESULTS The Data Safety and Monitoring Board recommended early trial closure after 49 patients were randomly assigned because of a significant PFS benefit in the LCT arm. With an updated median follow-up time of 38.8 months (range, 28.3 to 61.4 months), the PFS benefit was durable (median, 14.2 months [95% CI, 7.4 to 23.1 months] with LCT v 4.4 months [95% CI, 2.2 to 8.3 months] with MT/O; P = .022). We also found an OS benefit in the LCT arm (median, 41.2 months [95% CI, 18.9 months to not reached] with LCT v 17.0 months [95% CI, 10.1 to 39.8 months] with MT/O; P = .017). No additional grade 3 or greater toxicities were observed. Survival after progression was longer in the LCT group (37.6 months with LCT v 9.4 months with MT/O; P = .034). Of the 20 patients who experienced progression in the MT/O arm, nine received LCT to all lesions after progression, and the median OS was 17 months (95% CI, 7.8 months to not reached). CONCLUSION In patients with oligometastatic NSCLC that did not progress after front-line systemic therapy, LCT prolonged PFS and OS relative to MT/O. (C) 2019 by American Society of Clinical Oncology

引用

页码：1558 / 1565

页数：14

共 20 条

[1] Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study [J].

Cappuzzo, Federico ;

Ciuleanu, Tudor ;

Stelmakh, Lilia ;

Cicenas, Saulius ;

Szczesna, Aleksandra ;

Juhasz, Erzsebet ;

Esteban, Emilio ;

Molinier, Olivier ;

Brugger, Wolfram ;

Melezinek, Ivan ;

Klingelschmitt, Gaelle ;

Klughammer, Barbara ;

Giaccone, Giuseppe .

LANCET ONCOLOGY, 2010, 11 (06) :521-529

[2] Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study [J].

Ciuleanu, Tudor ;

Brodowicz, Thomas ;

Zielinski, Christoph ;

Kim, Joo Hang ;

Krzakowski, Maciej ;

Laack, Eckart ;

Wu, Yi-Long ;

Bover, Isabel ;

Begbie, Stephen ;

Tzekova, Valentina ;

Cucevic, Branka ;

Pereira, Jose Rodrigues ;

Yang, Sung Hyun ;

Madhavan, Jayaprakash ;

Sugarman, Katherine P. ;

Peterson, Patrick ;

John, William J. ;

Krejcy, Kurt ;

Belani, Chandra P. .

LANCET, 2009, 374 (9699) :1432-1440

[3] Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study [J].

Gomez, Daniel R. ;

Blumenschein, George R., Jr. ;

Lee, J. Jack ;

Hernandez, Mike ;

Ye, Rong ;

Camidge, D. Ross ;

Doebele, Robert C. ;

Skoulidis, Ferdinandos ;

Gaspar, Laurie E. ;

Gibbons, Don L. ;

Karam, Jose A. ;

Kavanagh, Brian D. ;

Tang, Chad ;

Komaki, Ritsuko ;

Louie, Alexander V. ;

Palma, David A. ;

Tsao, Anne S. ;

Sepesi, Boris ;

William, William N. ;

Zhang, Jianjun ;

Shi, Qiuling ;

Wang, Xin Shelley ;

Swisher, Stephen G. ;

Heymach, John V. .

LANCET ONCOLOGY, 2016, 17 (12) :1672-1682

[4] The evolutionary history of lethal metastatic prostate cancer [J].

Gundem, Gunes ;

Van Loo, Peter ;

Kremeyer, Barbara ;

Alexandrov, Ludmil B. ;

Tubio, Jose M. C. ;

Papaemmanuil, Elli ;

Brewer, Daniel S. ;

Kallio, Heini M. L. ;

Hoegnas, Gunilla ;

Annala, Matti ;

Kivinummi, Kati ;

Goody, Victoria ;

Latimer, Calli ;

O'Meara, Sarah ;

Dawson, Kevin J. ;

Isaacs, William ;

Emmert-Buck, Michael R. ;

Nykter, Matti ;

Foster, Christopher ;

Kote-Jarai, Zsofia ;

Easton, Douglas ;

Whitaker, Hayley C. ;

Neal, David E. ;

Cooper, Colin S. ;

Eeles, Rosalind A. ;

Visakorpi, Tapio ;

Campbell, Peter J. ;

McDermott, Ultan ;

Wedge, David C. ;

Bova, G. Steven .

NATURE, 2015, 520 (7547) :353-+

[5] OLIGOMETASTASES [J].

HELLMAN, S ;

WEICHSELBAUM, RR .

JOURNAL OF CLINICAL ONCOLOGY, 1995, 13 (01) :8-10

[6] Consolidative Radiotherapy for Limited Metastatic Non-Small-Cell Lung Cancer A Phase 2 Randomized Clinical Trial [J].

Iyengar, Puneeth ;

Wardak, Zabi ;

Gerber, David E. ;

Tumati, Vasu ;

Ahn, Chul ;

Hughes, Randall S. ;

Dowell, Jonathan E. ;

Cheedella, Naga ;

Nedzi, Lucien ;

Westover, Kenneth D. ;

Pulipparacharuvil, Suprabha ;

Choy, Hak ;

Timmerman, Robert D. .

JAMA ONCOLOGY, 2018, 4 (01)

[7] Tumor Self-Seeding by Circulating Cancer Cells [J].

Kim, Mi-Young ;

Oskarsson, Thordur ;

Acharyya, Swarnali ;

Nguyen, Don X. ;

Zhang, Xiang H. -F. ;

Norton, Larry ;

Massague, Joan .

CELL, 2009, 139 (07) :1315-1326

[8] Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial [J].

Ost, Piet ;

Reynders, Dries ;

Decaestecker, Karel ;

Fonteyne, Valerie ;

Lumen, Nicolaas ;

De Bruycker, Aurelie ;

Lambert, Bieke ;

Delrue, Louke ;

Bultijnck, Renee ;

Claeys, Tom ;

Goetghebeur, Els ;

Villeirs, Geert ;

De Man, Kathia ;

Ameye, Filip ;

Billiet, Ignace ;

Joniau, Steven ;

Vanhaverbeke, Friedl ;

De Meerleer, Gert .

JOURNAL OF CLINICAL ONCOLOGY, 2018, 36 (05) :446-+

[9] Stereotactic Ablative Radiation Therapy for the Comprehensive Treatment of Oligometastatic Tumors (SABR-COMET): Results of a Randomized Trial [J].

Palma, D. A. ;

Olson, R. A. ;

Harrow, S. ;

Gaede, S. ;

Louie, A. V. ;

Haasbeek, C. ;

Mulroy, L. A. ;

Lock, M. I. ;

Rodrigues, G. ;

Yaremko, B. P. ;

Schellenberg, D. ;

Ahmad, B. ;

Griffioen, G. ;

Senthi, S. ;

Liu, M. C. ;

Moore, K. ;

Currie, S. ;

Bauman, G. S. ;

Warner, A. ;

Senan, S. .

INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2018, 102 (03) :S3-S4

[10] Phase II Study of Pemetrexed and Carboplatin Plus Bevacizumab With Maintenance Pemetrexed and Bevacizumab As First-Line Therapy for Nonsquamous Non-Small-Cell Lung Cancer [J].

Patel, Jyoti D. ;

Hensing, Thomas A. ;

Rademaker, Alfred ;

Hart, Eric M. ;

Blum, Matthew G. ;

Milton, Daniel T. ;

Bonomi, Philip D. .

JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (20) :3284-3289

← 1 2 →