Optimum Sequencing of EGFR targeted therapy in NSCLC. Dr. Sema SEZGİN GÖKSU Akdeniz Univercity, Antalya, Turkey
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1 Optimum Sequencing of EGFR targeted therapy in NSCLC Dr. Sema SEZGİN GÖKSU Akdeniz Univercity, Antalya, Turkey
2 Lung cancer NSCLC SCLC adeno squamous EGFR ALK ROS1 BRAF HER2 KRAS
3 EGFR Transl Lung Cancer Res 2015;4(2):
4 1st line treatment
5 IPASS Gefitinib Tony S. Mok et al. N Engl J Med 2009;361:947-57
6 IPASS - PFS Tony S. Mok et al. N Engl J Med 2009;361:947-57
7 IPASS PFS according to EGFR mutation Tony S. Mok et al. N Engl J Med 2009;361:947-57
8 IPASS- ORR
9 IPASS OS Tony S. Mok et al. N Engl J Med 2009;361:947-57
10
11 EURTAC - PFS 9.7 m vs 5.2m
12 EURTAC - ORR ORR Erlotinib Chemotherapy %58 %15
13 EURTAC OS
14 AFATINIB Afatinib is a strong and selective, irreversible inhibitor of EGFR Afatinib inhibits all the members of ErbB receptor family As a result of irreversible binding, afatinib supresses kinase activity for a longer time compared with reversible TKI
15 LUX-Lung 3 and LUX-Lung 6
16 LUX-Lung 3 A- all population B- patients with common mutations J Clin Oncol 31: by American Society of Clinical Oncology
17 LUX-Lung 6 Lancet Oncol 2014; 15:
18 LUX-Lung 3 and LUX-Lung 6 OS
19 Does the mutation type matters?
20 Afatinib del19 del19 L858R exon 21 Lancet Oncol 2015; 16:
21 Afatinib uncommon mutations Lancet Oncol 2015; 16:
22 Afatinib uncommon mutations poor activity for patients with de-novo Thr790Met and exon 20 insertion mutations, for whom treatment with chemotherapy might be considered rather than EGFR inhibitors.
23 Does the drug choise matter? Which TKI? 1st generation TKI Gefitinib Erlotinib 2nd generation TKI Afatinib Dacomitinib 3rd generation TKI Osimertinib Rociletinib Olmutinib
24 LUX-Lung 7 Afatinib vs Gefitinib Annals of Oncology 28: , 2017
25 LUX-Lung patients R 160 Afatinib 159 Gefitinib Annals of Oncology 28: , 2017
26 LUX-Lung 7 Annals of Oncology 28: , 2017
27 Dacomitinib vs Gefitinib
28 ARCHER 1050
29 ARCHER 1050
30 ARCHER 1050
31 2nd line treatment Although EGFR TKIs are highly effective, acquired resistance occurs within months. Mechanisms of resistance: T790M mutation (%60) Downsteram signaling pathway mutations ( BRAF- PIK3A) Parallel signaling pathway activation ( MET, HER2, FGFR, AXL) Histologic transformation (%3)
32
33 Osimertinib Osimertinib is selective for EGFR-TKI-sensitizing mutations (L858R and exon 19 deletion) and T790M mutations
34 AURA 3 Metastatic NSCLC EGFR+ T790M+ Progression on 1st line EGFR TKI 2:1 Osimertinib 80 mg once daily Pemetrexed+ Cisplatin/Carboplatin The primary endpoint of the trial was PFS Secondary endpoints included overall survival (OS), overall response rate (ORR), duration of response (DoR), disease control rate (DCR), safety and measures of health-related quality of life (HRQoL) Tony Mok et al, NEJM 2017;376
35 AURA3 - PFS Tony Mok et al, NEJM 2017;376
36 AURA3 CNS Tony Mok et al, NEJM 2017;376
37
38 What if the Osimertinib comes to 1st line? LBA2_PR - Ramalingam SS, et al. Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with EGFRm advanced NSCLC: FLAURA.
39 FLAURA - 1st line Osimertinib- PFS LBA2_PR - Ramalingam SS, et al. Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with EGFRm advanced NSCLC: FLAURA.
40 FLAURA - 1st line Osimertinib- ORR LBA2_PR - Ramalingam SS, et al. Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with EGFRm advanced NSCLC: FLAURA.
41 FLAURA - 1st line Osimertinib- OS LBA2_PR - Ramalingam SS, et al. Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with EGFRm advanced NSCLC: FLAURA.
42 FLAURA - 1st line Osimertinib- safety LBA2_PR - Ramalingam SS, et al. Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with EGFRm advanced NSCLC: FLAURA.
43 What about T790M (-) patients? progression on 1st line EGFR TKI Chemotherapy Continue 1stline EGFR TKI beyond progression Clinical trial
44 Continue 1stline EGFR TKI beyond progression
45 Continue 1stline EGFR TKI beyond progression PFS: 5.4 months vs 5.4months OS: 17 2 months vs 14 8 months (HR 1 62, 95% CI ; p=0 03) favoring chemotherapy Jean-Charles Soria et al,lancet Oncology 2015
46 ASPIRATION: Erlotinib beyond progression
47 NSCLC EGFR mutation + Erlotinib Gefitinib Afatinib Dacomitinib Osimertinib T790M + Osimertinib T790M- Continue to 1st line in oligometastatic patients CT Another TKI? CT
48 Thank you
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Disclaimer This slide deck in its original and unaltered format is for educational purposes and is current as of April 2017. The content and views presented in this educational activity are those of the
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