CONTACT-01: A Randomized Phase III Trial of Atezolizumab plus Cabozantinib Versus Docetaxel for Metastatic Non-Small Cell Lung Cancer After a Checkpoint Inhibitor and Chemotherapy

被引：20

作者：

Neal, Joel ^{[1
]}

Pavlakis, Nick ^{[2
]}

Kim, Sang-We ^{[3
]}

Goto, Yasushi ^{[4
]}

Lim, Sun Min ^{[5
]}

Mountzios, Giannis ^{[6
]}

Fountzilas, Elena ^{[7
]}

Mochalova, Anastasia ^{[8
]}

Christoph, Daniel C. ^{[9
]}

Bearz, Alessandra ^{[10
]}

Quantin, Xavier ^{[11
]}

Palmero, Ramon ^{[12
]}

Antic, Vladan ^{[13
]}

Chun, Elaine ^{[14
]}

Edubilli, Tirupathi Rao ^{[15
]}

Lin, Ya-Chen ^{[14
]}

Huseni, Mahrukh ^{[14
]}

Ballinger, Marcus ^{[14
]}

Graupner, Vilma ^{[13
]}

Curran, Dominic ^{[16
]}

Vervaet, Piet ^{[16
]}

Newsom-Davis, Thomas ^{[17
]}

机构：

[1] Stanford Univ, Stanford Canc Inst, Palo Alto, CA 94304 USA

[2] Univ Sydney, Royal North Shore Hosp, St Leonards, Australia

[3] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea

[4] Natl Canc Ctr, Tokyo, Japan

[5] Yonsei Univ, Coll Med, Seoul, South Korea

[6] Henry Dunant Hosp Ctr, Athens, Greece

[7] Euromed Gen Clin Thessaloniki, Thessaloniki, Greece

[8] MEDSI Clin, Moscow, Russia

[9] Kliniken Essen Mitte, Evang, Essen, Germany

[10] NCI, CRO Aviano, CRO Aviano, Aviano, Italy

[11] Univ Montpellier, Montpellier Canc Inst, Inserm U1194, U1194, Montpellier, France

[12] Catalan Inst Oncol, Barcelona, Spain

[13] F Hoffmann La Roche Ltd, Basel, Switzerland

[14] Genentech Inc, South San Francisco, CA USA

[15] Roche Prod Ltd, Welwyn Garden City, England

[16] Exelixis, Alameda, CA USA

[17] Chelsea & Westminster Hosp, London, England

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2024年 / 42卷 / 20期

关键词：

OPEN-LABEL; PEMBROLIZUMAB; MULTICENTER; CARCINOMA; NIVOLUMAB;

D O I：

10.1200/JCO.23.02166

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSEAlthough checkpoint inhibitors have improved first-line treatment for non-small cell lung cancer (NSCLC), a therapeutic need remains for patients whose disease does not respond or who experience disease progression after anti-PD-L1/PD-1 immunotherapy. CONTACT-01 (ClinicalTrials.gov identifier: NCT04471428) evaluated atezolizumab plus cabozantinib versus docetaxel in patients with metastatic NSCLC who developed disease progression after concurrent or sequential treatment with anti-PD-L1/PD-1 and platinum-containing chemotherapy.METHODSThis multicenter, open-label, phase III trial randomly assigned patients 1:1 to atezolizumab 1,200 mg intravenously once every 3 weeks (q3w) plus cabozantinib 40 mg orally once daily or docetaxel 75 mg/m2 intravenously once every 3 weeks. The primary end point was overall survival (OS).RESULTSOne hundred eighty-six patients were assigned atezolizumab plus cabozantinib, and 180 docetaxel. Minimum OS follow-up was 10.9 months. Median OS was 10.7 months (95% CI, 8.8 to 12.3) with atezolizumab plus cabozantinib and 10.5 months (95% CI, 8.6 to 13.0) with docetaxel (stratified hazard ratio [HR], 0.88 [95% CI, 0.68 to 1.16]; P = .3668). Median progression-free survival was 4.6 months (95% CI, 4.1 to 5.6) and 4.0 months (95% CI, 3.1 to 4.4), respectively (stratified HR, 0.74 [95% CI, 0.59 to 0.92]). Serious adverse events (AEs) occurred in 71 (38.4%) patients receiving atezolizumab plus cabozantinib and 58 (34.7%) receiving docetaxel. Grade 3/4 treatment-related AEs occurred in 73 (39.5%) patients receiving atezolizumab plus cabozantinib and 58 (34.7%) receiving docetaxel. Grade 5 AEs occurred in 14 (7.6%) and 10 (6.0%) patients in the atezolizumab plus cabozantinib and docetaxel arms, respectively (treatment-related in four [2.2%] and one [0.6%], respectively).CONCLUSIONAtezolizumab plus cabozantinib after disease progression following anti-PD-L1/PD-1 immunotherapy and platinum-containing chemotherapy for metastatic NSCLC did not improve OS compared with docetaxel. Safety was consistent with known profiles of these agents.

引用

页码：2393 / 2403

页数：16

共 34 条

[1] Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma [J].

Abou-Alfa, G. K. ;

Meyer, T. ;

Cheng, A. -L. ;

El-Khoueiry, A. B. ;

Rimassa, L. ;

Ryoo, B. -Y. ;

Cicin, I. ;

Merle, P. ;

Chen, Y. H. ;

Park, J. -W. ;

Blanc, J. -F. ;

Bolondi, L. ;

Klumpen, H. -J. ;

Chan, S. L. ;

Zagonel, V. ;

Pressiani, T. ;

Ryu, M. -H. ;

Venook, A. P. ;

Hessel, C. ;

Borgman-Hagey, A. E. ;

Schwab, G. ;

Kelley, R. K. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 379 (01) :54-63

[2] Datopotamab deruxtecan (Dato-DXd) vs docetaxel in previously treated advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC): Results of the randomized phase III study TROPION-Lung01 [J].

Ahn, M. J. ;

Lisberg, A. ;

Paz-Ares, L. ;

Cornelissen, R. ;

Girard, N. ;

Pons-Tostivint, E. ;

Baz, D. Vicente ;

Sugawara, S. ;

Dols, M. Cobo ;

Perol, M. ;

Mascaux, C. ;

Poddubskaya, E. ;

Kitazono, S. ;

Hayashi, H. ;

Sands, J. ;

Hall, R. ;

Zhang, Y. ;

Zebger-Gong, H. ;

Uema, D. ;

Okamoto, I. .

ANNALS OF ONCOLOGY, 2023, 34 :S1305-S1306

[3] SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer [J].

Borghaei, H. ;

de Marinis, F. ;

Dumoulin, D. ;

Reynolds, C. ;

Theelen, W. S. M. E. ;

Percent, I. ;

Calderon, V. Gutierrez ;

Johnson, M. L. ;

Madroszyk-Flandin, A. ;

Garon, E. B. ;

He, K. ;

Planchard, D. ;

Reck, M. ;

Popat, S. ;

Herbst, R. S. ;

Leal, T. A. ;

Shazer, R. L. ;

Yan, X. ;

Harrigan, R. ;

Peters, S. .

ANNALS OF ONCOLOGY, 2024, 35 (01) :66-76

[4] Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer [J].

Borghaei, H. ;

Paz-Ares, L. ;

Horn, L. ;

Spigel, D. R. ;

Steins, M. ;

Ready, N. E. ;

Chow, L. Q. ;

Vokes, E. E. ;

Felip, E. ;

Holgado, E. ;

Barlesi, F. ;

Kohlhaeufl, M. ;

Arrieta, O. ;

Burgio, M. A. ;

Fayette, J. ;

Lena, H. ;

Poddubskaya, E. ;

Gerber, D. E. ;

Gettinger, S. N. ;

Rudin, C. M. ;

Rizvi, N. ;

Crino, L. ;

Blumenschein, G. R. ;

Antonia, S. J. ;

Dorange, C. ;

Harbison, C. T. ;

Finckenstein, F. Graf ;

Brahmer, J. R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (17) :1627-1639

[5] A CONFIDENCE-INTERVAL FOR THE MEDIAN SURVIVAL-TIME [J].

BROOKMEYER, R ;

CROWLEY, J .

BIOMETRICS, 1982, 38 (01) :29-41

[6] Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo-controlled, phase 3 trial [J].

Brose, Marcia S. ;

Robinson, Bruce ;

Sherman, Steven, I ;

Krajewska, Jolanta ;

Lin, Chia-Chi ;

Vaisman, Fernanda ;

Hoff, Ana ;

Hitre, Erika ;

Bowles, Daniel W. ;

Hernando, Jorge ;

Faoro, Leonardo ;

Banerjee, Kamalika ;

Oliver, Jennifer W. ;

Keam, Bhumsuk ;

Capdevila, Jaume .

LANCET ONCOLOGY, 2021, 22 (08) :1126-1138

[7] Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma [J].

Choueiri, T. K. ;

Powles, T. ;

Burotto, M. ;

Escudier, B. ;

Bourlon, M. T. ;

Zurawski, B. ;

Juarez, V. M. Oyervides ;

Hsieh, J. J. ;

Basso, U. ;

Shah, A. Y. ;

Suarez, C. ;

Hamzaj, A. ;

Goh, J. C. ;

Barrios, C. ;

Richardet, M. ;

Porta, C. ;

Kowalyszyn, R. ;

Feregrino, J. P. ;

Zolnierek, J. ;

Pook, D. ;

Kessler, E. R. ;

Tomita, Y. ;

Mizuno, R. ;

Bedke, J. ;

Zhang, J. ;

Maurer, M. A. ;

Simsek, B. ;

Ejzykowicz, F. ;

Schwab, G. M. ;

Apolo, A. B. ;

Motzer, R. J. .

NEW ENGLAND JOURNAL OF MEDICINE, 2021, 384 (09) :829-841

[8] Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial [J].

Choueiri, Toni K. ;

Escudier, Bernard ;

Powles, Thomas ;

Tannir, Nizar M. ;

Mainwaring, Paul N. ;

Rini, Brian I. ;

Hammers, Hans J. ;

Donskov, Frede ;

Roth, Bruce J. ;

Peltola, Katriina ;

Lee, Jae Lyun ;

Heng, Daniel Y. C. ;

Schmidinger, Manuela ;

Agarwal, Neeraj ;

Sternberg, Cora N. ;

McDermott, David F. ;

Aftab, Dana T. ;

Hessel, Colin ;

Old, Christian Scheff ;

Schwab, Gisela ;

Hutson, Thomas E. ;

Pal, Sumanta ;

Motzer, Robert J. .

LANCET ONCOLOGY, 2016, 17 (07) :917-927

[9]

Exelixis, Cabometyx (Cabozantinib) tablets for oral use prescribing information

[10] Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer [J].

Gandhi, L. ;

Rodriguez-Abreu, D. ;

Gadgeel, S. ;

Esteban, E. ;

Felip, E. ;

De Angelis, F. ;

Domine, M. ;

Clingan, P. ;

Hochmair, M. J. ;

Powell, S. F. ;

Cheng, S. Y. -S. ;

Bischoff, H. G. ;

Peled, N. ;

Grossi, F. ;

Jennens, R. R. ;

Reck, M. ;

Hui, R. ;

Garon, E. B. ;

Boyer, M. ;

Rubio-Viqueira, B. ;

Novello, S. ;

Kurata, T. ;

Gray, J. E. ;

Vida, J. ;

Wei, Z. ;

Yang, J. ;

Raftopoulos, H. ;

Pietanza, M. C. ;

Garassino, M. C. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 378 (22) :2078-2092

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