Virtual Library
Start Your Search
Daniel SW Tan
Author of
-
+
MTE 20 - Liquid Biopsy (Sign Up Required) (ID 551)
- Event: WCLC 2017
- Type: Meet the Expert
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 07:00 - 08:00, Room 303 + 304
-
+
MTE 20.01 - Recent Advances in Liquid Biopsy (ID 8117)
07:00 - 07:30 | Presenting Author(s): Daniel SW Tan
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
OA 09 - EGFR TKI Resistance (ID 663)
- Event: WCLC 2017
- Type: Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Thanyanan Reungwetwattana, Lecia V Sequist
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 301 + 302
-
+
OA 09.07 - Clonality of c-MET Copy Number Gain as a Determinant of Primary TKI Resistance in EGFR-Mutant NSCLC (ID 8887)
12:05 - 12:15 | Author(s): Daniel SW Tan
- Abstract
- Presentation
Background:
cMET activation is a valid mechanism of secondary TKI resistance in EGFR mutation-positive (EGFR-M+) NSCLC. However, its role in the treatment-naïve setting remains unclear. We sought to ascertain the prevalence and clinical impact of co-existing cMET copy number gain(CNG) in TKI-naïve early-stage and metastatic EGFR-M+ NSCLC.
Method:
Multi-region SNP array analysis (n=59 sectors) was performed on 13 early-stage resected EGFR-M+ NSCLC. cMET FISH was performed in a separate cohort of 206 metastatic treatment-naïve EGFR-M+ patients, all of whom were treated with first-line EGFR TKIs. We defined cMET-high as CNG≥5 copies, with an additional criteria of MET:CEP7 ratio >2.0 for amplification. Time-to-treatment failure(TTF) in patients cMET-high/low was estimated by Kaplan-Meier method and compared using log-rank test. A cell line from a cMET-high patient exhibiting primary TKI resistance was established.
Result:
Relative to median ploidy across sectors, 7/13(53.8%) early-stage EGFR-M+ tumors showed cMET CNG in at least one sector, with majority displaying(n=6/7) copy number intra-tumor heterogeneity. In the metastatic cohort, 55/206 patients (26.7%) were found to be cMET-high at diagnosis: 6(10.9%) had MET amplification, 49(89.1%) MET polysomy, with the following distribution: 5-6 copies(n=11), 6-8 copies(n=32), and >8 copies(n=12). We next evaluated clinical outcomes stratified by MET-high v low: median TTF was 14.7m(12.2–NE) vs 14.6m(12.7–16.5), p=0.985 respectively, with no significant difference in response rates(RR) to EGFR TKI (66.7%v73.7%; p=0.940). Further stratification by level of CNG did not reveal any differences in RR (5-6 copies:75.0%, 6-8 copies:63.0%, >8 copies:71.4%; p=0.868). In MET-high amplified group, only 2/6 (33.3%) had a partial response to EGFR TKI. In the cohort with suboptimal TKI response (PFS<6m, n=22), we did not observe significant enrichment for MET-high, relative to rest of the cohort (36.4%v25.5%, p=0.278). Finally, in 6 patients with progressive disease within 4 weeks of initiating EGFR TKI, 2/6(33.3%) were MET-high. In a cell line model derived from a MET-high patient (L858R, cMET:7.3 copies) genomic profiling of cell colonies revealed clonal cMET CNG and subclonal EGFR, with the patient demonstrating clinical response to crizotinib.
Conclusion:
Although up to 26% of TKI-naïve EGFR-M+ NSCLC harbor high cMET CNG by FISH, this occurs on the background of a highly variegated copy number landscape. cMET CNG alone does not significantly impact clinical outcomes to EGFR TKI, with the exception of one patient with a clonal cMET-driven tumor. Our data challenges the utility of arbitrary copy number thresholds to define clinically relevant MET pathway dysregulation and underscores the importance of targeting dominant truncal drivers.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
-
+
P1.01-012 - Ceritinib in Anaplastic Lymphoma Kinase (ALK)+ NSCLC Patients Pretreated With Only Crizotinib: ASCEND-1 Subgroup Analysis (ID 8972)
09:30 - 09:30 | Author(s): Daniel SW Tan
- Abstract
Background:
In phase 1 ASCEND-1 study (NCT01283516), ceritinib 750 mg/day (fasted) demonstrated durable whole-body and intracranial responses in both anaplastic lymphoma kinase inhibitor (ALKi)-naïve and ALKi-pretreated patients with ALK-rearranged non-small cell lung cancer (NSCLC). Here, we report the efficacy and safety of ceritinib in patients who were pretreated with crizotinib only from the ASCEND-1 study.
Method:
Patients with ALK+ NSCLC who were enrolled globally received ceritinib 750 mg/day (fasted). Efficacy and safety were evaluated in a subset of patients who had received prior crizotinib only (no other prior antineoplastic therapy). Data cut-off was May 03, 2016.
Result:
Overall, 246 patients with ALK+ NSCLC (83 ALKi-naïve and 163 ALKi-pretreated) received ≥1 dose of ceritinib, of whom, 26 had received prior crizotinib only. Among the 26 crizotinib-pretreated patients, 11 (42.3%) had baseline brain metastases, of which, 7 received prior radiotherapy, 6 (23.1%) had an ECOG performance status of 0, and 24 (92.3%) patients had stage IV disease. The median time from initial diagnosis to ceritinib initiation was 10.5 months (range, 2.4-33.0). At data cut-off, the median duration of exposure (range) was 41.0 weeks (2.9-180.4). In the 26 crizotinib-pretreated patients, per investigator assessment, the overall response rate was 65.4% (95% confidence interval [CI]: 44.3, 82.8), and the disease control rate was 80.8% (95% CI: 60.6, 93.4) (Table). The most frequently reported grade 3/4 adverse events (AEs), regardless of study drug relationship, were ALT increased (30.8%), AST increased (15.4%), diarrhea (11.5%), nausea (7.7%), fatigue (7.7%), and blood alkaline phosphatase increased (7.7%). All 26 patients discontinued treatment due to disease progression (n=12), consent withdrawal (n=6), AEs (n=2), administrative problems (n=4), or death (n=2).
*Median value derived from summary statistics; **Median value estimated by Kaplan-Meier method.Investigator Assessment N=26 Blinded Independent Review Committee Assessment N=26 Best overall response Complete response (CR), n (%) 1 (3.8%) 1 (3.8%) Partial response (PR), n (%) 16 (61.5%) 15 (57.7%) Stable disease (SD), n (%) 4 (15.4%) 5 (19.2%) Progressive disease (PD), n (%) 2 (7.7%) 1 (3.8%) Unknown, n (%) 3 (11.5%) 4 (15.4%) Overall response rate (ORR), % [95% CI] 65.4% [44.3-82.8] 61.5% [40.6-79.8] Disease control rate (DCR), % [95% CI] 80.8% [60.6-93.4] 80.8% [60.6-93.4] Median time to response*, weeks [95% CI] 6.1 [5.1-23.6] 6.4 [5.1-14.0] Median DOR**, months [95% CI] 8.3 [4.2-11.2] 8.5 [3.0-13.6] Median PFS**, months [95% CI] 8.5 [5.3-9.9] 8.2 [4.4-15.2]
Conclusion:
Ceritinib demonstrated durable efficacy in crizotinib-pretreated patients with ALK-rearranged NSCLC. Safety was consistent with the overall ASCEND-1 study population.
-
+
P2.04 - Clinical Design, Statistics and Clinical Trials (ID 705)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
-
+
P2.04-005 - GEOMETRY Mono-1: Phase II, Multicenter Study of MET Inhibitor Capmatinib (INC280) in EGFR Wt, MET-Dysregulated Advanced NSCLC (ID 8961)
09:30 - 09:30 | Author(s): Daniel SW Tan
- Abstract
Background:
Amplification of MET leading to oncogenic signaling occurs in 3‒5% of newly diagnosed EGFR wild type (wt) non-small cell lung cancer (NSCLC) cases with decreasing incidence at higher levels of amplification. Mutations in MET leading to exon 14 deletion (METΔ[ex14]) also occur in 2–4% of adenocarcinoma and 1–2% of other NSCLC subsets. Capmatinib (INC280) is a potent and selective MET inhibitor that has shown strong evidence of antitumor activity in a phase I study in patients with EGFR wt advanced NSCLC harboring MET amplification and METΔ[ex14].
Method:
This phase II, multicenter study (NCT02414139) was designed to confirm the clinical activity of capmatinib in patients with advanced NSCLC by MET amplification and METΔ[ex14] status. Eligible patients (≥18 years of age, Eastern Cooperative Oncology Group Performance Status 0–1) must have ALK-negative, EGFR wt, stage IIIB/IV NSCLC (any histology). Centrally assessed MET amplification (gene copy number [GCN]) and mutation status is used to assign patients to one of the below cohorts: Pretreated with 1–2 prior systemic lines of therapy for advanced setting (cohorts 1–4): 1a: MET amplification GCN ≥10 (n=69) 1b: MET amplification GCN ≥6 and <10 (n=69) 2: MET amplification GCN ≥4 and <6 (n=69) 3: MET amplification GCN <4 (n=69) 4: METΔ[ex14] mutation regardless of MET GCN (n=69) Treatment naïve (cohorts 5a and 5b): 5a: MET amplification GCN ≥10 and no METΔ[ex14] mutation (n=27) 5b: METΔ[ex14] mutation regardless of MET GCN (n=27) Capmatinib 400 mg tablets are orally administered twice daily on a continuous dosing schedule 12 hours apart. Primary and key secondary endpoints are overall response rate (ORR) and duration of response (DOR), respectively (blinded independent review assessment). Other secondary endpoints include investigator-assessed ORR, DOR, time to response, disease control rate, progression-free survival (independent and investigator assessment), safety, and pharmacokinetics. Enrollment is ongoing in 25 countries. Cohorts 1b, 2, and 3 are now closed to enrollment; cohorts 1a and 4 continue to enroll patients who have received 1–2 prior lines of therapy in the advanced setting, and cohorts 5a and 5b are open for enrollment of treatment-naïve patients. Responses have been seen in both MET-amplified and MET-mutated patients irrespective of the line of therapy.
Result:
Section not applicable
Conclusion:
Section not applicable
-
+
P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
-
+
P3.01-017 - Clinical Outcomes of Patients with EGFR T790M + NSCLC on Osimertinib (ID 8802)
09:30 - 09:30 | Author(s): Daniel SW Tan
- Abstract
Background:
Osimertinib (AZD9291) is a third-generation EGFR TKI specific against T790M resistance mutations in patients with metastatic EGFR-mutant (EGFRm+) NSCLC after prior first-line TKI therapy. We aimed to evaluate the clinical efficacy of osimertinib in patients treated under the AZD9291 Early Access Program (EAP) at our local institution.
Method:
This retrospective study included 57 patients who were enrolled on the AZD9291 EAP between Jul 2015 and Nov 2016 after being tested T790M+ on tumor (by direct Sanger sequencing or Roche COBAS EGFR mutation test v2) and/or plasma (cfDNA) specimens (by Lung Colon Panel v2 or ARMS PCR). Of these patients, 52 were treated with osimertinib. Tumor responses were independently assessed by radiologists using RECIST 1.1 criteria. DOR, PFS and OS were estimated by Kaplan-Meier method.
Result:
The median age at diagnosis was 58 years (range: 35-76), 80.7% patients were non-smokers, 89.5% had ECOG 0-2, 96.5% had adenocarcinoma subtype and 87.8% had either EGFR exon 19/ exon 21 mutations. Median line of therapy when osimertinib was administered was third-line (range 2nd – 9th), and 30 (53%) had brain metastasis at osimertinib initiation. RR by RECIST 1.1 was 46% (95% CI 32.2 – 60.5%) (4 CR + 20 PR) with median DOR of 8.7 months. With median follow-up of 6.2 months from osimertinib initiation, median PFS was 10.3 months (95% CI 7.52 to 15.87 months). For the 52 patients treated with osimertinib, EGFR T790M mutation was tested on the following specimens: tumor-only (n=43), plasma-only (n=25), and both (n=17). In patients with paired tumor/plasma T790M testing, 4/17 had concordant results (RR 75%), while 13 patients with discordant results [T790M+ in 8 tumor-only: RR 25% (95% CI 3.2% - 65.1%) or in 5 plasma-only: RR 40% (95% CI 5.3% - 85.3%)] had overall RR 31% (95% CI 9.1% – 61.4%). ECOG status was associated with PFS by univariable analysis, with higher ECOG 2-4 associated with shorter PFS (HR=6.54, 95% CI: 2.48 to 17.26; p<0.001) than ECOG 0-1. Line of osimertinib treatment and presence of brain metastases at osimertinib initiation were not associated with clinical outcome.
Conclusion:
Osimertinib is effective in patients with advanced EGFR T790M+ NSCLC after progression on prior EGFR TKI, regardless of presence/ absence of CNS metastasis or line of therapy. Notwithstanding ongoing optimization of plasma-based assays, T790M tumor-plasma discordance in our patient cohort is likely a reflection of overall burden of T790M subclones, and may represent a potential negative predictive biomarker of response to osimertinib.
-
+
YI 01 - Young Investigator and First Time Attendee Session (ID 588)
- Event: WCLC 2017
- Type: Young Investigator
- Track: Education/Publication/Career Development
- Presentations: 1
- Moderators:Peter Goldstraw, Giorgio Vittorio Scagliotti
- Coordinates: 10/15/2017, 08:00 - 11:30, F201 + F202 (Annex Hall)
-
+
YI 01.05 - Investigator Initiated Trials (ID 7849)
08:55 - 09:10 | Presenting Author(s): Daniel SW Tan
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
