Selpercatinib in RET fusion-positive non-small-cell lung cancer (SIREN): a retrospective analysis of patients treated through an access program

被引：42

作者：

Illini, Oliver ^{[1
]}

Hochmair, Maximilian Johannes ^{[1
]}

Fabikan, Hannah ^{[2
]}

Weinlinger, Christoph ^{[2
]}

Tufman, Amanda ^{[3
]}

Swalduz, Aurelie ^{[4
]}

Lamberg, Kristina ^{[5
]}

Hashemi, Sayed M. S. ^{[6
]}

Huemer, Florian ^{[7
]}

Vikstrom, Anders ^{[8
]}

Wermke, Martin ^{[9
]}

Absenger, Gudrun ^{[10
]}

Addeo, Alfredo ^{[11
]}

Banerji, Shantanu ^{[12
]}

Calles, Antonio ^{[13
]}

Clarke, Stephen ^{[14
]}

Di Maio, Massimo ^{[15
,16
]}

Durand, Alice ^{[17
]}

Duruisseaux, Michael ^{[18
,19
,20
]}

Itchins, Malinda ^{[21
]}

Kaaranien, Okko-Sakari ^{[22
]}

Krenn, Florian ^{[23
]}

Laack, Eckart ^{[24
]}

de Langen, Adrianus Johannes ^{[25
]}

Mohorcic, Katja ^{[26
]}

Pall, Georg ^{[27
]}

Passaro, Antonio ^{[28
]}

Prager, Gerald ^{[29
]}

Rittmeyer, Achim ^{[30
]}

Rothenstein, Jeffrey

Schumacher, Michael

Woell, Ewald

Valipour, Arschang

机构：

[1] Karl Landsteiner Inst Lung Res & Pulm Oncol, Dept Resp & Crit Care Med, Klin Floridsdorf, Brunner Str 68, A-1210 Vienna, Austria

[2] Karl Landsteiner Inst Lung Res & Pulm Oncol, Klin Floridsdorf, Vienna, Austria

[3] LMU Munchen, Klinikum Univ Muenchen, Med Klin & Poliklin, Mitglied Deutsch Zentrums Lungenforsch, CPC M, Munich, Bayern, Germany

[4] Ctr Leon Berard, Lyon, France

[5] Uppsala Univ Hosp, Dept Pulm & Allerg Dis, Uppsala, Sweden

[6] Vrije Univ Amsterdam, Med Ctr, Amsterdam UMC, Canc Ctr Amsterdam, Amsterdam, Netherlands

[7] Ludwig Boltzmann Inst Lung Hlth, Dept Resp Care, Klin Penzing, Vienna, Austria

[8] Linkoping Univ Hosp, Pulm clin, Linkoping, Sweden

[9] Tech Univ Dresden, Med Fac C G Carus, NCT UCC Early Clin Trial, Unit Dresden, Dresden, Germany

[10] Med Univ Graz, Dept Oncol, Graz, Austria

[11] Univ Hosp Geneva, Oncol Dept, Geneva, Switzerland

[12] Univ Manitoba, Res Inst Oncol & Hematol, Canc Care Manitoba, Winnipeg, MB, Canada

[13] Univ Gregorio Maranon, Hosp Gen, Med Oncol Dept, Madrid, Spain

[14] Royal North Shore Hosp, Med Oncol Unit, St Leonards, NSW, Australia

[15] Univ Turin, Dept Oncol, Turin, Italy

[16] Ordine Mauriziano Hosp, Med Oncol, Turin, Italy

[17] Univ Lyon, France Univ Claude Bernard Lyon 1, Hosp Civils Lyon, Canc Inst Lyon,Louis Pradel Hosp,Resp Dept, Lyon, France

[18] Hosp Civils Lyon, Canc Inst, Louis Pradel Hosp, Resp Dept, Lyon, France

[19] Canc Res Ctr Lyon, Oncopharmacol Lab, Lyon, France

[20] Univ Lyon, Univ Claude Bernard Lyon 1, Lyon, France

[21] Royal North Shore Hosp, Med Oncol Unit, St Leonards, NSW, Australia

[22] Kuopio Univ Hosp, Ctr Canc, Kuopio, Finland

[23] LKH Hochsteiermark Standort Leoben, Abt Lungenkrankheiten, Leoben, Austria

[24] Studiengesellschaft Hamatoonkol Hamburg, Hamburg, Germany

[25] Netherlands Canc Inst, Amsterdam, Netherlands

[26] Univ Clin Goln, Med Oncol Unit, Golnik, Slovenia

[27] Univ Innsbruck Hosp, Dept Internal Med V Hematol Oncol, Innsbruck, Austria

[28] European Inst Oncol IRCCS, Div Thorac Oncol, Milan, Italy

[29] Comprehens Canc Ctr Vienna, Dept Med I, Vienna, Austria

[30] LKI Lungenfachklin Immenhausen, Dept Thorac Oncol, Immenhausen, Germany

来源：

THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY | 2021年 / 13卷

关键词：

non-small cell lung cancer (NSCLC); real-world data; RET gene fusions; selpercatinib; targeted therapy; tyrosine kinase inhibitor (TKI); TARGETING RET; CLINICAL-OUTCOMES; OSIMERTINIB; LESSONS;

D O I：

10.1177/17588359211019675

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Introduction: Rearranged during transfection (RET) gene fusions are rare genetic drivers in non-small cell lung cancer (NSCLC). Selective RET-inhibitors such as selpercatinib have shown therapeutic activity in early clinical trials; however, their efficacy in the real-world setting is unknown. Methods: A retrospective efficacy and safety analysis was performed on data from RET fusion-positive NSCLC patients who participated in a selpercatinib access program (named patient protocol) between August 2019 and January 2021. Results: Data from 50 patients with RET fusion-positive advanced NSCLC treated with selpercatinib at 27 centers in 12 countries was analyzed. Most patients were Non-Asian (90%), female (60%), never-smokers (74%), with a median age of 65 years (range, 38-89). 32% of the patients had known brain metastasis at the time of selpercatinib treatment. Overall, 13 patients were treatment-naive, while 37 were pretreated with a median of three lines of therapy (range, 1-8). The objective response rate (ORR) was 68% [95% confidence interval (CI), 53-81] in the overall population. The disease control rate was 92%. The median progression-free survival was 15.6 months (95% CI, 8.8-22.4) after a median follow-up of 9 months. In patients with measurable brain metastases (n = 8) intracranial ORR reached 100%. In total, 88% of patients experienced treatment-related adverse events (TRAEs), a large majority of them being grade 1 or 2. The most common grade > 3 TRAEs were increased liver enzyme levels (in 10% of patients), prolonged QTc time (4%), abdominal pain (4%), hypertension (4%), and fatigue/asthenia (4%). None of patients discontinued selpercatinib treatment for safety reasons. No new safety concerns were observed, nor where there any treatment-related death. Conclusions: In this real-world setting, the selective RET-inhibitor selpercatinib demonstrated durable systemic and intracranial antitumor activity in RET fusion-positive NSCLC and was well tolerated.

引用

页数：17

共 29 条

[1] RET Rearrangement as a Predictor of Unresponsiveness to Immunotherapy in Non-Small Cell Lung Cancer: Report of Two Cases with Review of the Literature [J].

Baglivo, Sara ;

Ludovini, Vienna ;

Moretti, Riccardo ;

Bellezza, Guido ;

Sidoni, Angelo ;

Roila, Fausto ;

Metro, Giulio .

ONCOLOGY AND THERAPY, 2020, 8 (02) :333-339

[2] ESMO recommendations on the standard methods to detect RET fusions and mutations in daily practice and clinical research [J].

Belli, C. ;

Penault-Llorca, F. ;

Ladanyi, M. ;

Normanno, N. ;

Scoazec, J-Y ;

Lacroix, L. ;

Reis-Filho, J. S. ;

Subbiah, V ;

Gainor, J. F. ;

Endris, V ;

Repetto, M. ;

Drilon, A. ;

Scarpa, A. ;

Andre, F. ;

Douillard, J-Y ;

Curigliano, G. .

ANNALS OF ONCOLOGY, 2021, 32 (03) :337-350

[3] Targeting RET-rearranged non-small-cell lung cancer: future prospects [J].

Bronte, Giuseppe ;

Ulivi, Paola ;

Verlicchi, Alberto ;

Cravero, Paola ;

Delmonte, Angelo ;

Crino, Lucio .

LUNG CANCER-TARGETS AND THERAPY, 2019, 10 :27-36

[4] KIF5B-RET fusions in Chinese patients with nonsmall cell lung cancer [J].

Cai, Weijing ;

Su, Chunxia ;

Li, Xuefei ;

Fan, Lihong ;

Zheng, Limou ;

Fei, Ke ;

Zhou, Caicun .

CANCER, 2013, 119 (08) :1486-1494

[5]

Calles Antonio, 2020, Am Soc Clin Oncol Educ Book, V40, P372, DOI 10.1200/EDBK_280795

[6] Real-World Data for Regulatory Decision Making: Challenges and Possible Solutions for Europe [J].

Cave, Alison ;

Kurz, Xavier ;

Arlett, Peter .

CLINICAL PHARMACOLOGY & THERAPEUTICS, 2019, 106 (01) :36-39

[7] Case of Fatal Immune-Related Skin Toxicity From Sequential Use of Osimertinib After Pembrolizumab: Lessons for Drug Sequencing in Never-Smoking Non-Small-Cell Lung Cancer [J].

Cui, Wanyuan ;

Cotter, Chantal ;

Sreter, Katherina Bernadette ;

Heelan, Kara ;

Creamer, Daniel ;

Basu, Tanya N. ;

Handy, Jonathan ;

Walsh, Sarah ;

Popat, Sanjay .

JCO ONCOLOGY PRACTICE, 2020, 16 (12) :842-+

[8] Efficacy of Selpercatinib in RET Fusion-Positive Non-Small-Cell Lung Cancer [J].

Drilon, A. ;

Oxnard, G. R. ;

Tan, D. S. W. ;

Loong, H. H. F. ;

Johnson, M. ;

Gainor, J. ;

McCoach, C. E. ;

Gautschi, O. ;

Besse, B. ;

Cho, B. C. ;

Peled, N. ;

Weiss, J. ;

Kim, Y. -J. ;

Ohe, Y. ;

Nishio, M. ;

Park, K. ;

Patel, J. ;

Seto, T. ;

Sakamoto, T. ;

Rosen, E. ;

Shah, M. H. ;

Barlesi, F. ;

Cassier, P. A. ;

Bazhenova, L. ;

De Braud, F. ;

Garralda, E. ;

Velcheti, V. ;

Satouchi, M. ;

Ohashi, K. ;

Pennell, N. A. ;

Reckamp, K. L. ;

Dy, G. K. ;

Wolf, J. ;

Solomon, B. ;

Falchook, G. ;

Ebata, K. ;

Nguyen, M. ;

Nair, B. ;

Zhu, E. Y. ;

Yang, L. ;

Huang, X. ;

Olek, E. ;

Rothenberg, S. M. ;

Goto, K. ;

Subbiah, V. .

NEW ENGLAND JOURNAL OF MEDICINE, 2020, 383 (09) :813-824

[9] Clinical outcomes with pemetrexed-based systemic therapies in RET-rearranged lung cancers [J].

Drilon, A. ;

Bergagnini, I. ;

Delasos, L. ;

Sabari, J. ;

Woo, K. M. ;

Plodkowski, A. ;

Wang, L. ;

Hellmann, M. D. ;

Joubert, P. ;

Sima, C. S. ;

Smith, R. ;

Somwar, R. ;

Rekhtman, N. ;

Ladanyi, M. ;

Riely, G. J. ;

Kris, M. G. .

ANNALS OF ONCOLOGY, 2016, 27 (07) :1286-1291

[10] Frequency of Brain Metastases and Multikinase Inhibitor Outcomes in Patients With RET-Rearranged Lung Cancers [J].

Drilon, Alexander ;

Lin, Jessica J. ;

Filleron, Thomas ;

Ni, Ai ;

Milia, Julie ;

Bergagnini, Isabella ;

Hatzoglou, Vaios ;

Velcheti, Vamsidhar ;

Offin, Michael ;

Li, Bob ;

Carbone, David P. ;

Besse, Benjamin ;

Mok, Tony ;

Awad, Mark M. ;

Wolf, Jurgen ;

Owen, Dwight ;

Camidge, D. Ross ;

Riely, Gregory J. ;

Peled, Nir ;

Kris, Mark G. ;

Mazieres, Julien ;

Gainor, Justin F. ;

Gautschi, Oliver .

JOURNAL OF THORACIC ONCOLOGY, 2018, 13 (10) :1595-1601

← 1 2 3 →