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Medical Oncology
Published in: Medical Oncology 5/2018

01-05-2018 | Review Article

Precision medicine against ALK-positive non-small cell lung cancer: beyond crizotinib

Authors: Biagio Ricciuti, Andrea De Giglio, Carmen Mecca, Cataldo Arcuri, Sabrina Marini, Giulio Metro, Sara Baglivo, Angelo Sidoni, Guido Bellezza, Lucio Crinò, Rita Chiari

Published in: Medical Oncology | Issue 5/2018

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Abstract

Anaplastic lymphoma kinase (ALK) rearrangements represent the molecular driver of a subset of non-small cell lung cancers (NSCLCs). Despite the initial response, virtually all ALK-positive patients develop an acquired resistance to the ALK inhibitor crizotinib, usually within 12 months. Several next-generation ALK inhibitors have been developed in order to overcome crizotinib limitation, providing an unprecedented survival for this subset of patients. The aim of this review to summarize the current knowledge on ALK tyrosine kinase inhibitors (TKIs) in the treatment of advanced ALK-positive NSCLC, focusing on the role of novel ALK inhibitors in this setting. In addition, we will discuss their role in the pharmacological management of ALK-positive brain metastasis. Next-generation ALK inhibitors showed an impressive clinical activity in ALK-positive NSCLC, also against the sanctuary site of CNS. Sequential therapy with ALK TKIs appears to be effective in patients who fail a first ALK TKI and translates in clinically meaningful benefit. However, these agents display different activity profiles against crizotinib resistance mutation; therefore re-genotyping the disease at progression in order to administer the right TKI to the right patient is going to be necessary to correctly tailor the treatment. To avoid repeated invasive procedure, noninvasive methods to detect and monitor ALK rearrangement are under clinical investigation.
Literature
1.
2.
Howlader N, Noone AM, Krapcho M, et al., editors. SEER cancer statistics review, 1975–2012. Bethesda: National Cancer Institute; 2015.
3.
Shaw AT, Solomon B. Targeting anaplastic lymphoma kinase in lung cancer. Clin Cancer Res. 2011;17(8):2081–6.CrossRefPubMed
4.
Hallberg B, Palmer RH. Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology. Nat Rev Cancer. 2013;13(10):685–700.CrossRefPubMed
5.
Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448(7153):561–6.CrossRefPubMed
6.
Koivunen JP, Mermel C, Zejnullahu K, et al. EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clin Cancer Res. 2008;14(13):4275–83.CrossRefPubMedPubMedCentral
7.
Morris SW, Kirstein MN, Valentine MB, et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma. Science. 1994;263(5151):1281–4.CrossRefPubMed
8.
Boi M, Zucca E, Inghirami G, et al. Advances in understanding the pathogenesis of systemic anaplastic large cell lymphomas. Br J Haematol. 2015;168(6):771–83.CrossRefPubMed
9.
Takeuchi K, Choi YL, Soda M, et al. Multiplex reverse transcription-PCR screening for EML4-ALK fusion transcripts. Clin Cancer Res. 2008;14(20):6618–24.CrossRefPubMed
10.
Li T, Maus MK, Desai SJ, et al. Large-scale screening and molecular characterization of EML4-ALK fusion variants in archival non-small-cell lung cancer tumor specimens using quantitative reverse transcription polymerase chain reaction assays. J Thorac Oncol. 2014;9(1):18–25.CrossRefPubMed
11.
Shackelford RE, Vora M, Mayhall K, et al. ALK-rearrangements and testing methods in non-small cell lung cancer: a review. Genes Cancer. 2014;5(1–2):1–14.PubMedPubMedCentral
12.
Peled N, Palmer G, Hirsch FR, et al. Next-generation sequencing identifies and immunohistochemistry confirms a novel crizotinib-sensitive ALK rearrangement in a patient with metastatic non-small-cell lung cancer. J Thorac Oncol. 2012;7(9):e14–6.CrossRefPubMedPubMedCentral
13.
Sun JM, Choi YL, Won JK, et al. A dramatic response to crizotinib in a non-small-cell lung cancer patient with IHC-positive and FISH-negative ALK. J Thorac Oncol. 2012;7:e36–8.CrossRefPubMed
14.
Thunnissen E, Bubendorf L, Dietel M, et al. EML4-ALK testing in non-small cell carcinomas of the lung: a review with recommendations. Virchows Arch. 2012;461(3):245–57.CrossRefPubMedPubMedCentral
15.
Zhang YG, Jin ML, Li L, et al. Evaluation of ALK rearrangement in Chinese non-small cell lung cancer using FISH, immunohistochemistry, and real-time quantitative RT-PCR on paraffin embedded tissues. PLoS ONE. 2013;8:e64821.CrossRefPubMedPubMedCentral
16.
Geiss GK, Bumgarner RE, Birditt B, et al. Direct multiplexed measurement of gene expression with color-coded probe pairs. Nat Biotechnol. 2008;26(3):317–25.CrossRefPubMed
17.
Hiley CT, Le Quesne J, Santis G, et al. Challenges in molecular testing in non-small-cell lung cancer patients with advanced disease. Lancet. 2016;388(10048):1002–11.CrossRefPubMed
18.
Lin E, Li L, Guan Y, et al. Exon array profiling detects EML4-ALK fusion in breast, colorectal, and non-small cell lung cancers. Mol Cancer Res. 2009;7(9):1466–76.CrossRefPubMed
19.
Camidge DR, Bang YJ, Kwak EL, et al. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from phase 1 study. Lancet Oncol. 2012;13(10):1011–9.CrossRefPubMedPubMedCentral
20.
Kim DW, Ahn MJ, Shi Y, et al. Results of a global phase II study with crizotinib in advanced ALK-positive non-small cell lung cancer (NSCLC). J Clin Oncol. 2012;30(15):Suppl7433.
21.
Blackhall F, Ross Camidge D, Shaw AT, et al. Final results of the large-scale multinational trial PROFILE 1005: efficacy and safety of crizotinib in previously treated patients with advanced/metastatic ALK-positive non-small-cell lung cancer. ESMO Open. 2017;2(3):e000219.CrossRefPubMedPubMedCentral
22.
Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368(25):2385–94.CrossRefPubMed
23.
Shaw AT, Pasi AJ, Besse B, et al. Crizotinib vs chemotherapy in ALK+ advanced non-small cell lung cancer (NSCLC): final survival results from PROFILE 1007. J Clin Oncol. 2016;34(15):Suppl.9066.
24.
Solomon B, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;37(23):2167–77.CrossRef
25.
Heuckmann JM, Balke-Want H, Malchers F, et al. Differential protein stability and ALK inhibitor sensitivity of EML4-ALK fusion variants. Clin Cancer Res. 2012;18:4682–90.CrossRefPubMed
26.
Mengoli MC, Barbieri F, Bertolini F, et al. K-RAS mutations indicating primary resistance to crizotinib in ALK-rearranged adenocarcinomas of the lung: report of two cases and review of the literature. Lung Cancer. 2016;93:55–8.CrossRefPubMed
27.
Iacono D, Chiari R, Metro G, et al. Future options for ALK-positive non-small cell lung cancer. Lung Cancer. 2015;87(3):211–9.CrossRefPubMed
28.
Van der Wekken AJ, Saber A, Hiltermann TJ, et al. Resistance mechanism after tyrosine kinase inhibitors afatinib and crizotinib in non-small cell lung cancer, a review of the literature. Crit Rev Oncol Hematol. 2016;100:107–16.CrossRefPubMed
29.
Isozaki H, Takigawa N, Kiura K. Mechanisms of acquired resistance to ALK inhibitors and the rationale for treating ALK-positive lung cancer. Cancers (Basel). 2015;7(2):763–83.CrossRef
30.
Boland JM, Jang JS, Li J, et al. MET and EGFR mutations identified in ALK rearranged pulmonary adenocarcinoma: molecular analysis of 25 ALK-positive cases. J Thorac Oncol. 2013;8(5):574–81.CrossRefPubMed
31.
Rossing HH, Grauslund M, Urbanska EM, et al. Concomitant occurrence of EGFR (epidermal growth factor receptor) and KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutations in an ALK (anaplastic lymphoma kinase)-positive lung adenocarcinoma patient with acquired resistance to crizotinib: a case report. BMC Res Notes. 2013;6:489.CrossRefPubMedPubMedCentral
32.
33.
Ji C, Zhang L, Cheng Y, et al. Induction of autophagy contributes to crizotinib resistance in ALK-positive lung cancer. Cancer Biol Ther. 2014;15(5):570–7.CrossRefPubMedPubMedCentral
34.
Miyamoto S, Ikushima S, Ono R, et al. Transformation to small-cell lung cancer as a mechanism of acquired resistance to crizotinib and alectinib. Jpn J Clin Oncol. 2016;46(2):170–3.PubMed
35.
Costa DB, Shaw AT, Ou SH, et al. Clinical experience with crizotinib in patients with advanced ALK-rearranged non-small-cell lung cancer and brain metastases. J Clin Oncol. 2015;33(17):1881–8.CrossRefPubMedPubMedCentral
36.
Metro G, Lunardi G, Floridi P, et al. CSF concentration of crizotinib in two ALK-positive non-small-cell lung cancer patients with CNS metastases deriving clinical benefit from treatment. J Thorac Oncol. 2015;10(5):e26–7.CrossRefPubMed
37.
Weickhardt AJ, Scheier B, Burke JM, et al. Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer. J Thorac Oncol. 2012;7(12):1807–14.CrossRefPubMedPubMedCentral
38.
Sasaky T, Koivunen J, Ogino A, et al. A novel ALK secondary mutation and EGFR signalling cause resistance to ALK kinase inhibitors. Cancer Res. 2011;71(18):6051–60.CrossRef
39.
Kim S, Kim TM, Kim DW, et al. Heterogeneity of genetic changes associated with acquired crizotinib resistance in ALK rearranged lung cancer. J Thorac Oncol. 2013;8:415–22.CrossRefPubMed
40.
Marsilje TH, Pei W, Chen B, et al. Synthesis, structure-activity relationship, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and 2 clinical trials. J Med Chem. 2013;56(14):5675–90.CrossRefPubMed
41.
Friboulet L, Li N, Katayama R, et al. The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discov. 2014;4(6):662–73.CrossRefPubMedPubMedCentral
42.
Kim DW, Mehra R, Tan DSW, et al. Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): updated results from the multicentre, open-label, phase 1 trial. Lancet Oncol. 2016;17(4):452–63.CrossRefPubMedPubMedCentral
43.
Crinò L, Ahn MJ, De Marinis F, et al. Multicenter phase II study of whole-body and intracranial activity with ceritinib in patients with ALK-rearranged non-small-cell lung cancer previously treated with chemotherapy and crizotinib: results from ASCEND-2. J Clin Oncol. 2016;34(24):2866–73.CrossRefPubMed
44.
Felip E, Orlov S, Park K, et al. ASCEND-3: A single-arm, open-label, multicenter phase II study of ceritinib in ALKi-naïve adult patients (pts) with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC). J Clin Oncol. 2015;33:abstr 8060.
45.
Soria JC, Tan DSW, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017;389(10072):917–29.CrossRefPubMed
46.
Shaw AT, Kim TM, Crinò L, et al. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2017;18(7):874–86.CrossRefPubMed
47.
Cho BC, Kim DW, Bearz A, et al. ASCEND-8: a randomized phase 1 study of ceritinib, 450 mg or 600 mg, taken with a low-fat meal versus 750 mg in fasted state in patients with anaplastic lymphoma kinase (ALK)-rearranged metastatic non-small cell lung cancer (NSCLC). J Thorac Oncol. 2017;12(9):1357–67.CrossRefPubMed
48.
Kinoshita K, Asoh K, Furuichi N, et al. Design and synthesis of a highly selective, orally active and potent anaplastic lymphoma kinase inhibitor (CH5424802). Bioorg Med Chem. 2012;20(3):1271–80.CrossRefPubMed
49.
Kodama T, Tsukaguchi T, Yoshida M, et al. ALK inhibitor alectinib with potent antitumor activity in models of crizotinib resistance. Cancer Lett. 2014;351(2):215–21.CrossRefPubMed
50.
Sakamoto H, Tsukaguchi T, Hiroshima S, Kodama T, Kobayashi T, Fukami TA, et al. CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell. 2011;19(5):679–90.CrossRefPubMed
51.
Seto T, Kiura K, Nishio M, et al. CH5424802 (RO5424802) for patients with ALK rearranged advanced non-small-cell lung cancer (AF-001JP study): a single-arm, open label, phase 1-2 study. Lancet Oncol. 2013;14(7):590–8.CrossRefPubMed
52.
Gadgeel SM, Gandhi L, Riely GJ, et al. Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study. Lancet Oncol. 2014;15(10):1119–28.CrossRefPubMed
53.
Shaw AT, Gandhi L, Gadgeel S, et al. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol. 2016;17(2):234–42.CrossRefPubMed
54.
Ou SHI, Ahn JS, De Petris L, et al. Alectinib in crizotinib-refractory ALK-rearranged non-small-cell lung cancer: a phase II global study. J Clin Oncol. 2016;34(7):661–8.CrossRefPubMed
55.
Peters S, Camidge DR, Shaw AT, et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017;377(9):829–38.CrossRefPubMed
56.
Hida T, Nokihara H, Kondo M, et al. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet. 2017;390(10089):29–39.CrossRefPubMed
57.
Bauer TM, Shaw AT, Solomon B, et al. Phase I/II study of PF-06463922, an ALK/ROS1 tyrosine kinase inhibitor, in patients with advanced non-small-cell lung cancer harboring specific molecular alterations. J Clin Oncol. 2015;33:abstrTPS2620.
58.
Johnson TW, Richardson PF, Bailey S, et al. Discovery of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a macrocyclic inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) with preclinical brain exposure and broad-spectrum potency against ALK-resistant mutations. J Med Chem. 2014;57(11):4720–44.CrossRefPubMed
59.
Zou HY, Li Q, Engstrom LD, et al. PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations. Proc Natl Acad Sci USA. 2015;112(11):3493–8.CrossRefPubMedPubMedCentral
60.
Zou HY, Friboulet L, Kodack DP, et al. PF-06463922, an ALK/ROS1 inhibitor, overcomes resistance to first and second generation ALK inhibitors in preclinical models. Cancer Cell. 2015;28(1):70–81.CrossRefPubMedPubMedCentral
61.
Doebele RC, Pilling AB, Aisner DL, et al. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res. 2012;18(5):1472–82.CrossRefPubMedPubMedCentral
62.
Shaw AT, Felip E, Bauer TM, et al. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017;18(12):1590–9.CrossRefPubMed
63.
Solomon B, Shaw A, Ou S, et al. Phase 2 study of lorlatinib in patients with advanced ALK+/ROS1+ non-small-cell lung cancer. J Thorac Oncol. 2017;11S2:OA0506.
64.
Zhang S, Wang F, Keats J, et al. AP26113, a potent ALK inhibitor, overcomes mutations in EML4-ALK that confer resistance to PF-02341066. Cancer Res. 2010;70(Suppl.8):abstrLB-298.CrossRef
65.
Squillace R, Anjum R, Miller D, et al. AP26113 possesses pan-inhibitory activity versus crizotinib-resistant ALK mutants and oncogenic ROS1 fusions. Cancer Res. 2013;73(Suppl. 8):5655.CrossRef
66.
Rivera V, Wang F, Anjum R, et al. AP26113 is a dual ALK/EGFR inhibitor: characterization against EGFR T790M in cell and mouse models of NSCLC. Cancer Res. 2012;72(Suppl 1):abstract1794.CrossRef
67.
Langer CJ, Gettinger SN, Bazhenova L, et al. Activity and safety of brigatinib (BRG) in patients (pts) with ALK+ non–small cell lung cancer (NSCLC): phase (ph) 1/2 trial results. J Clin Oncol. 2016;34(Suppl.15):abstr9057.
68.
Kim DW, Tiseo M, Ahn MJ, et al. Brigatinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small-cell lung cancer: a randomized, multicenter phase II trial. J Clin Oncol. 2017;35:2490–8.CrossRefPubMed
69.
Farago AF, Le LP, Zheng Z, et al. Durable clinical response to entrectinib in NTRK1-rearranged non-small cell lung cancer. J Thorac Oncol. 2015;10(12):1670–4.CrossRefPubMedPubMedCentral
70.
71.
Ardini E, Menichincheri M, Banfi P, et al. In vitro and in vivo activity of NMS-E628 against ALK mutations resistant to Xalkori. Mol Cancer Ther. 2011;10:A232.CrossRef
72.
Ardini E, Menichincheri M, De Ponti C, et al. Characterization of NMS-E628, a small molecule inhibitor of anaplastic lymphoma kinase with antitumor efficacy in ALK-dependent lymphoma and non-small cell lung cancer models. Mol Cancer Ther. 2009;8:A243.CrossRef
73.
Drilon A, Siena S, Ou SI, et al. Safety and antitumor activity of the multitargeted pan-TRK, ROS1, and ALK inhibitor entrectinib: combined results from two phase I trials (ALKA-372-001 and STARTRK-1). Cancer Discov. 2017;7(4):400–9.CrossRefPubMedPubMedCentral
74.
Toyokawa G, Inamasu E, Shimamatsu S, et al. Identification of a novel ALKG1123S mutation in a patient with ALK-rearranged non-small-cell lung cancer exhibiting resistance to ceritinib. J Thorac Oncol. 2015;10:e55–7.CrossRefPubMed
75.
Tchekmedyian N, Ali SM, Miller VA, et al. Acquired ALK l1152r mutation confers resistance to ceritinib and predicts response to alectinib. J Thorac Oncol. 2016;11:e87–8.CrossRefPubMed
76.
Ou SHI, Azada M, Hsiang DJ, et al. Next-generation sequencing reveals a novel NSCLCALK f1174v mutation and confirms ALKG1202R mutation confers high-level resistance to alectinib (ch5424802/ro5424802) in ALK-rearranged NSCLC patients who progressed on crizotinib. J Thorac Oncol. 2014;9(4):549–53.CrossRef
77.
Ceccon M, Mologni L, Giudici G, et al. Treatment efficacy and resistance mechanisms using the second-generation ALK inhibitor ap26113 in human npm-ALK-positive anaplastic large cell lymphoma. Mol Cancer Res. 2015;13(4):775–83.CrossRefPubMed
78.
Gainor JF, Dardaei L, Yoda S, et al. Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer. Cancer Discov. 2016;6(10):1118–33.CrossRefPubMedPubMedCentral
79.
Mori M, Ueno Y, Konagai S, et al. The selective anaplastic lymphoma receptor tyrosine kinase inhibitor ASP3026 induces tumor regression and prolongs survival in non-small cell lung cancer model mice. Mol Cancer Ther. 2014;13(2):329–40.CrossRefPubMed
80.
Maitland ML, Ou SHI, Tolcher AW, et al. Safety, activity, and pharmacokinetics of an oral anaplastic lymphoma kinase (ALK) inhibitor, ASP3026, observed in a “fast follower” phase 1 trial design. J Clin Oncol. 2014;32(5s):abstr2624.
81.
Arkenau H, Sachdev J, Mita M, et al. Phase (Ph) 1/2a study of TSR-011, a potent inhibitor of ALK and TRK, in advanced solid tumors including crizotinib-resistant ALK positive non-small cell lung cancer. J Clin Oncol. 2015;33:abstr8063.
82.
Lovly CM, Heuckmann JM, de Stanchina E, et al. Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors. Cancer Res. 2011;71(14):4920–31.CrossRefPubMedPubMedCentral
83.
Horn L, Infante JR, Blumenschein GR, et al. A phase I trial of X-396, a novel ALK inhibitor, in patients with advanced solid tumors. J Clin Oncol. 2014;32(5s):abstr8030.
84.
Cheng M, Quail MR, Gingrich DE, et al. CEP-28122, a highly potent and selective orally active inhibitor of anaplastic lymphoma kinase with antitumor activity in experimental models of human cancers. Mol Cancer Ther. 2012;11(3):670–9.CrossRefPubMed
85.
Kodama T, Hasegawa M, Takanashi K, et al. Antitumor activity of the selective ALK inhibitor alectinib in models of intracranial metastases. Cancer Chemother Pharmacol. 2014;74(5):1023–8.CrossRefPubMed
86.
Gadgeel S, Shaw T, Govindan R, et al. Pooled analysis of CNS response to alectinib in two studies of pre-treated ALK+ NSCLC. J Thorac Oncol. 2015;10(9Suppl 2):S238(abstract).
87.
Metro G, Lunardi G, Bennati C, et al. Alectinib’s activity against CNS metastases from ALK-positive non-small cell lung cancer: a single institution case series. J Neurooncol. 2016;129(2):355–61.CrossRefPubMed
88.
Tiseo M, Huber RM, Hochmair MJ, et al. Brigatinib in ALK-positive NSCLC pts with intracranial CNS metastases in 2 clinical trials. Ann Oncol. 2017;28(Suppl.2):ii28–51.
89.
Riely GJ, Yu HA, Stephens D, et al. A phase 1 study of crizotinib and ganetespib (STA-9090) in ALK positive lung cancers. J Clin Oncol. 2015;33:abstr 8064.
90.
Ota K, Azuma K, Kawahara A, et al. Induction of PD-L1 expression by the EML4-ALK oncoprotein and downstream signaling pathways in non-small cell lung cancer. Clin Cancer Res. 2015;21(17):4014–21.CrossRefPubMed
91.
Spigel DR, Reynolds C, Waterhouse D, et al. Phase 1/2 study of the safety and tolerability of nivolumab plus crizotinib for the first-line treatment of ALK translocation–positive advanced non-small cell lung cancer (CheckMate 370). J Thorac Oncol. 2018; pii:S1556-0864(18)30176-X.
92.
Felip E, De Braud FG, Maur M, et al. Ceritinib plus nivolumab (NIVO) in patients (pts) with anaplastic lymphoma kinase positive (ALK+) advanced non-small cell lung cancer (NSCLC). J Clin Oncol. 2017;35(15suppl):2502.
93.
Chiari R, Metro G, Iacono D, et al. Clinical impact of sequential treatment with ALK-TKIs in patients with advanced ALK positive non-small cell lung cancer: results of a multicenter analysis. Lung Cancer. 2015;90(2):255–60.CrossRefPubMed
94.
Gainor JF, Tan DSW, De Pas T, et al. Progression-free and overall survival in ALK-positive NSCLC patients treated with sequential crizotinib and ceritinib. Clin Cancer Res. 2015;21(12):2745–52.CrossRefPubMedPubMedCentral
95.
Ito K, Hataji O, Kobayashi H, et al. Sequential therapy with crizotinib and alectinib in ALK-rearranged non-small-cell lung cancer-a multicenter retrospective study. J Thorac Oncol. 2017;12(2):390–6.CrossRefPubMed
Metadata
Title
Precision medicine against ALK-positive non-small cell lung cancer: beyond crizotinib
Authors
Biagio Ricciuti
Andrea De Giglio
Carmen Mecca
Cataldo Arcuri
Sabrina Marini
Giulio Metro
Sara Baglivo
Angelo Sidoni
Guido Bellezza
Lucio Crinò
Rita Chiari
Publication date
01-05-2018
Publisher
Springer US
Published in
Medical Oncology / Issue 5/2018
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-018-1133-4

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Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

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Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

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Prof. Florian Limbourg
Prof. Anoop Chauhan
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