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Young-Chul Kim
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MA08 - Clinical Trials in Brain Metastases (ID 906)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 15:15 - 16:45, Room 203 BD
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MA08.07 - Real World Data of Osimertinib in Patients with Central Nervous System (CNS) Metastasis in ASTRIS Korean Subset. (ID 13581)
15:50 - 15:55 | Author(s): Young-Chul Kim
- Abstract
- Presentation
Background
More than 40% of non-small cell lung cancer (NSCLC) patients develop CNS metastasis in their lifetime. Osimertinib is a third-generation EGFR-TKI which selectively inhibits both EGFR-sensitizing and EGFR T790M resistance mutations. Clinical studies have shown superior efficacy of osimertinib in CNS compared to platinum chemotherapy. Treatment efficacy in patients with or without CNS metastasis were observed within the second interim analysis of ASTRIS (NCT02474355). Data cut-off (DCO) was 20 October 2017.
a9ded1e5ce5d75814730bb4caaf49419 Method
In ASTRIS, advanced NSCLC patients with a locally confirmed T790M mutation, WHO performance status 0-2, prior EGFR-TKI therapy were enrolled. Patients with stable CNS metastases were allowed. The primary endpoint was overall survival (OS); other endpoints included investigator-assessed response rate (RR), progression-free survival (PFS), time to treatment discontinuation (TTD) and safety. These endpoints were also analyzed according to presence of CNS metastasis.
4c3880bb027f159e801041b1021e88e8 Result
A total of 466 patients received at least one dose of osimertinib 80mg from 31 Korean sites. CNS metastasis was evaluated in 310 patients and was present in 211 (68.1%) patients (CNS-met); 181 brain only, 1 leptomeningeal only, 29 both. 99 (31.9%) patients did not have CNS metastasis (CNS-no), and 155 patients were not evaluated (CNS-ne). At DCO, 236 patients (50.6%) were ongoing and median duration of exposure was 11.2 (0–19) months. In patients evaluable for response, defined as at least one dose of osimertinib and one response assessment, RR was 71.0% (320/451; 95% CI, 66.5–75.1): Patients with (N=211), without (N=99), and not-evaluated CNS metastasis (N=155) had RR of 68% (134/197; 95% CI, 61.0-74.5), 79.6% (78/98; 95% CI, 70.3-87.1), and 69.7% (108/155; 95% CI, 61.8-76.8), respectively. Median PFS was 12.4 months (95% CI, 11.1-13.6 months); 10.8 months (95% CI, 9.5-11.5) in CNS-met,11.0 months (95% CI, 9.2-14.5) in CNS-no, and 15.1 months (95% CI, 13.6-18.2) in CNS-ne. Median TTD was 16.5 months (95% CI, 14.1-NC); 11.2 months (95% CI, 9.4-14.8) in CNS-met, 14.7 months (95% CI, 12.2-NC) in CNS-no, and NC (95% CI, 15.5-NC) in CNS-ne. OS was not reached (data maturity: 19.7%). Serious adverse event (AE) regardless of causality were reported in 116 patients (24.9%) and AEs leading to death in 13 patients (2.8%). ILD/pneumonitis-like events were reported in 8 patients (1.7%), and QTc prolongation in 7 patients (1.5%).
8eea62084ca7e541d918e823422bd82e Conclusion
In ASTRIS Korean subset, patients with or without CNS metastasis had comparable efficacy outcome. This data continues to support osimertinib’s clinical benefit on EGFRm T790M NSCLC patients with CNS metastasis.
6f8b794f3246b0c1e1780bb4d4d5dc53Only 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.
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-11 - Named Patient Use Program for Afatinib in Advanced NSCLC with Progression on Prior Therapy: Experience from Asian Centers (ID 12968)
16:45 - 18:00 | Author(s): Young-Chul Kim
- Abstract
Background
A global named patient use (NPU) program for afatinib in patients with advanced/metastatic NSCLC who had progressed during prior therapy was conducted between May 2010 and January 2016 (Cappuzzo F et al, Future Oncol 2018). Here we describe treatment outcomes for patients at Asian centers.
a9ded1e5ce5d75814730bb4caaf49419 Method
Eligible patients had progressed after clinical benefit on prior erlotinib/gefitinib and/or had an activating EGFR/HER2 mutation, had exhausted all other treatments, and were ineligible for afatinib trials. Patients received afatinib (starting dose:30-50 mg/day). Dose modifications were allowed as tolerated. Time to treatment failure (TTF) was calculated from treatment initiation to discontinuation. Adverse event (AE) reporting was mandatory.
4c3880bb027f159e801041b1021e88e8 Result
Data were collected from 2242 NSCLC patients across 10 Asian countries. Patients were heavily pretreated, 62% received ≥2 prior chemotherapy lines, and for most, afatinib was 4th-line therapy; almost all had received erlotinib/gefitinib (Table 1). 97% of patients with known tumor status were EGFR mutation-positive (m+). Median TTF was 7.6 months overall, and 7.2 months in patients with EGFR m+ tumors (Table 1). TTF was >12 months in patients with EGFR exon20 insertions and Her2 mutations. ORR was numerically higher in patients with exon20 insertions and G719X/L861Q/S761I mutations than other subgroups (Table 1). Disease control rate was 78% overall. The most frequently reported AEs were rash and diarrhea; no new/unexpected safety signals were identified.
Table 1. Named patient use (NPU) program for afatinib in advanced/metastatic NSCLC: results from Asian centers Total number of patients 2242 Age; years, median 61 Female/male; % 60/40 Any prior treatment; n (%) 2223/2242 (99.2) Prior erlotinib and/or gefitinib; n (%) 2202/2223 (99.1) Prior erlotinib only; n (%) 866/2202 (39) Prior gefitinib only; n (%) 927/2202 (42) Prior lines of chemotherapy ≥3, 32%; ≥2, 62%; 1, 23%; 0, 15% Prior lines of systemic therapy ≥4, 37%; ≥3, 65%; 2, 21%; 1, 14%; 0, 0% EGFR m+; n (%) 1240/1281 (97) Specified EGFR mutation; n (%) 1101/1240 (89) TTF; months* n ORR, % n All patients with data available 7.6 1550 24.4 431 EGFR m+ 7.2 834 27.7 267 EGFR mutation specified 6.5 740 - - Common mutations (Del19 or L858R) 6.4 692 27.4 230 Uncommon mutations (all) 8.0 84 30.3 33 T790M 6.0 34 21.1 19 G719X, L861Q, or S761I 7.8 28 42.9 7 Exon 20 insertion 18.0 25 42.9 7 Her2 m+ 12.2 12 14.2 7 p.A775 G776insYVMA 12.4 7 25.0 4 *median
m+ve, mutation-positive; ORR, objective response rate;
TTF, time to treatment failure
8eea62084ca7e541d918e823422bd82e Conclusion
This analysis from Asian countries in the afatinib NPU program revealed clinically meaningful TTF/ORR in this heavily pre-treated and refractory advanced NSCLC patient population, including activity in common and uncommon EGFR mutations. TTF was numerically longer in patients with uncommon mutations (particularly EGFR exon20 insertions) and HER2 mutations than in those with common EGFR mutations. The safety profile of afatinib was consistent with non-Asian centers.
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P1.01-77 - Osimertinib in the First-Line Treatment of Non-Small Cell Lung Cancer Harboring Activating EGFR Mutation from Circulating Tumor DNA (ID 13686)
16:45 - 18:00 | Author(s): Young-Chul Kim
- Abstract
Background
Osimertinib is a potent, irreversible third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for both EGFR activating and T790M resistant mutation. In this trial, the treatment efficacy of osimertinib was assessed in previously untreated patients with advanced or metastatic non-small cell lung carcinoma (NSCLC) harboring the EGFR activating mutation, which was detected from circulating tumor DNA (ctDNA) combined with tumor genotyping.
a9ded1e5ce5d75814730bb4caaf49419 Method
Venous blood sampling was performed from the patients with EGFR activating mutation confirmed by tissue genotyping. To extract ctDNA from the plasma, 15 mL of peripheral blood was withdrawn and centrifuged, immediately before storage. CobasTM v2 and PANA MutyperTM were used for ctDNA genotyping. Patients with the EGFR activating mutation, detected from ctDNA, were enrolled and received a once-daily administration of osimertinib, 80 mg. The primary endpoint was objective response rate (ORR), and secondary endpoints were ctDNA test sensitivity, progression-free survival (PFS), duration of response (DoR), and safety of osimertinib treatment (ClinicalTrials.gov, Identifier: NCT02769286).
4c3880bb027f159e801041b1021e88e8 Result
Thirty-nine patients with activating EGFR mutations in tumor genotyping were screened from February 2017, and the enrollment of the last patient was completed in March 2018. The ctDNA of 29 patients was positive for activating EGFR mutation, and 19 patients were enrolled (exon 19 deletion, n=11; L858R or L861Q, n=7; G719A, n=1). Median age was 70 years (range 32-84) and the majority of patients had brain metastasis (15/19, 78.9%). In the response-evaluable population (n=17), ORR was 64.7% (11/17) and DCR was 94.1% (16/17). According to EGFR mutation type of tumor genotyping, patients with exon 19 deletion showed more favorable ORR (8/9, 88.9%) than patients with exon 21 L858R/L861Q (3/7, 42.9%). In patients evaluable for CNS response (n=14), DCR of brain metastasis was 100.0% (14/14). The sensitivity of the ctDNA tests for activating EGFR mutation was 74.4% when using both tests, and 61.5% (Mutyper) or 64.1% (Cobas V2) with either test. Only one patient experienced drug-related interstitial pneumonia of grades ≥3 and resulted in drug discontinuation. Survival data including PFS was not matured (2/19, 10.5%) and the analysis will be followed.
8eea62084ca7e541d918e823422bd82e Conclusion
Osimertinib had favorable efficacy in first-line treatment of NSCLC harboring the EGFR activating mutation, detected from ctDNA combined with tumor genotyping, even though in patients with old age and brain metastasis.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P1.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 944)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.12-07 - Time to the End of Thoracic Radiotherapy Affects to Survival Outcomes Greater than Radiation Dose in Limited Stage Small Cell Lung Cancer (ID 13607)
16:45 - 18:00 | Author(s): Young-Chul Kim
- Abstract
Background
Early thoracic radiotherapy (TRT) concurrent with chemotherapy and radiation doses of 45 Gy given 1.5 Gy bid still has taken a seat as a standard treatment option for limited-stage small cell lung cancer (LS-SCLC). We aim to search the association between radiation parameters and survival outcomes in LS-SCLC patients who undertaken more than 45 Gy of TRT.
a9ded1e5ce5d75814730bb4caaf49419 Method
One hundred and one patients with LS-SCLC who completed TRT between August 2005 and March 2014 were reviewed retrospectively. Median age was 64 years (43-80) and male to female was 88 vs. 13. Stage IIIA was 30 and IIIB was 55, respectively. TRT was performed using 3-dimensional conformal radiation therapy (3DCRT) and delivered using 2Gy single fraction per day in 73.2% of patients. The median dose TRT was 50 Gy (45-65), and all patients received concurrent chemoradiotherapy. PCI was combined in 56 (55.4%) patients.
4c3880bb027f159e801041b1021e88e8 Result
The median survival for all patients was 26.9 months. Local failure occurred in 41 patients (40.5%), and distant metastasis was noted in 54 patients (53.4%). The 3-year local control, progression-free survival (PFS), and overall survival (OS) rates were 52.0%, 29.5%, and 56.4%, respectively. On univariate analysis, the American Joint Committee on Cancer stage (p<0.001), timing of TRT (≤2 vs, >2 cycles, p=0.017), tumor response (CR vs. PR, p=0.015), the duration from the start date of chemotherapy to the end of TRT (SER) (≤70 vs >70 days, p=0.025), and PCI (p=0.003) were the significant predictors of OS and stage (p<0.001) and PCI (p=0.017) were the significant predictors in PFS. Multivariate analysis revealed that stage (hazard ratio [HR], 3.61; 95% CI, 2.15-6.07) was the only significant factor in PFS and stage (HR, 2.49; 95% CI, 1.56-3.98), SER (HR, 1.93; 95% CI, 1.22-3.07), PCI (HR, 0.52; 95% CI, 0.33-0.84), and tumor response (HR, 1.76; 95% CI, 1.12 – 2.77) were the significant predictors in OS. There was one fatal radiation pneumonitis. Grade 3 radiation pneumonitis and esophagitis was shown in 7 (6.9%) vs. 7 (6.9%) patients, respectively. Grade 3 and 4 leukopenia was shown in 30 (29.7%) vs. 11 (10.8%) patients and febrile neutropenia was 9 (8.9%) vs. 1 (0.9%) patients, respectively.
8eea62084ca7e541d918e823422bd82e Conclusion
SER less than 70 days was a significant predictors of OS in LS-SCLC patients who received more than 45 Gy of TRT concurrently with chemotherapy. We could not find any significant positive survival benefits of TRT dose or BED escalation in our patients groups.
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P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.01-77 - Clinical Characteristics of Korean Lung Cancer Patients with Programmed Death-Ligand 1 Expression (ID 12770)
12:00 - 13:30 | Author(s): Young-Chul Kim
- Abstract
Background
Programmed death-ligand 1 (PD-L1) is a transmembrane protein that binds to the programmed death-1 (PD-1) receptor and anti-PD-1 therapy enables the immune response against tumors. The aim of this study was to assess the clinical and pathologic characteristics of PD-L1 positive lung cancer patients in Korea. And we examined correlation between immunohistochemical assays.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively reviewed the clinical and pathologic data of pathologically proven lung cancer patients, and collected 267 cases of formalin-fixed, paraffin-embedded tissue sample from single institution. PD-L1 expression was detected by qualitative immunohistochemical assay using Monoclonal Mouse Anti-PD-L1, Clone 22C3. PD-L1 protein expression is determined by using Tumor Proportion Score (TPS), which is the percentage of viable tumor cells showing partial or complete membrane staining. We categorized according to the percentage of TPS; more than 1% or more than 50%. Among 267 patients, 34 were analyzed by both 22C3 and SP263 assays. We examined the concordance correlation between IHC assays.
4c3880bb027f159e801041b1021e88e8 Result
A total of 267 patients were enrolled and major histologic types were adenocarcinoma (69.3%). The majority was smoker (67.4%) and clinical stage IV (60.7%). Thirty one (11.6%) cases of EGFR mutation and 17 (6.4%) cases of ALK FISH positive were included. The patients who showed TPS ≥ 1% and 50% were 116 (42%) and 58 (21%), respectively. More than 1% of TPS group was consisted of adenocarcinoma (67.8%), squamous cell carcinoma (29.6%), and small cell carcinoma (1.9%) histology. And more than 50% of TPS group was composed of adenocarcinoma (72.4%), squamous cell carcinoma (22.4%). More than 1% of TPS group was significantly older than less than 1% of TPS group (64.83 ± 9.38 vs. 61.73 ± 10.78 years, p=0.014). The rate of poorly differentiated pathology was significantly higher in TPS ≥ 1% group (40.8% vs. 25.8%) and TPS ≥ 50% group (53.2% vs. 27.2%). There was no difference in smoking, EGFR mutation, ALK rearrangement status or biopsy site. Among 34 patients analyzed by both 22C3 and SP 263, 27 patients showed positive by both 22C3 and SP263, at the cut-off of 1% or higher. The concordance correlation coefficient was 0.826 (95% confidence interval: 0.736-0.916).
8eea62084ca7e541d918e823422bd82e Conclusion
In Korean lung cancer patients, PD-L1 positive group defined as TPS ≥ 1% was older than negative group. And major histology was poorly differentiated non-small cell lung cancer in both TPS ≥ 1% and 50% groups. And our results showed a high correlation between PD-L1 IHC expression data analyzed by 22C3 and SP263 assays.
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PL02 - Presidential Symposium - Top 5 Abstracts (ID 850)
- Event: WCLC 2018
- Type: Plenary Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 08:15 - 09:45, Plenary Hall
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PL02.01 - Overall Survival with Durvalumab Versus Placebo After Chemoradiotherapy in Stage III NSCLC: Updated Results from PACIFIC (ID 14701)
08:15 - 08:25 | Author(s): Young-Chul Kim
- Abstract
- Presentation
Background
In the global, Phase 3 PACIFIC study (Antonia 2017; NCT02125461), durvalumab significantly improved progression-free survival (PFS) versus placebo in Stage III, unresectable NSCLC patients without progression after chemoradiotherapy (CRT) (stratified HR, 0.52; 95% CI, 0.42–0.65; P<0.001). This was the first major advance in this disease setting for many years. Here we report the second primary endpoint overall survival (OS) for PACIFIC.
Patients with WHO PS 0/1 (any PD-L1 tumor status) who received ≥2 cycles of platinum-based CRT were randomized (2:1) 1–42 days post-CRT to durvalumab 10 mg/kg IV Q2W or placebo up to 12 months, stratified by age, sex, and smoking history. Primary endpoints were PFS from randomization (blinded independent central review; RECIST v1.1) and OS (interim analysis reported). Secondary endpoints included time to death or distant metastasis (TTDM) and PFS2 (time to second progression) from randomization and safety. Time to first/second subsequent therapy or death (TFST/TSST) were supportive assessments for PFS/PFS2.
Between May 2014 and April 2016, 713 patients were randomized of whom 709 received treatment (durvalumab, n=473; placebo, n=236). As of March 22, 2018 (data cutoff), median follow-up duration was 25.2 months (range, 0.2–43.1). After discontinuation, 41.0% and 54.0% in the durvalumab and placebo groups received subsequent anticancer therapy; overall, 8.0% and 22.4% received additional immunotherapy. Durvalumab significantly improved OS versus placebo (stratified HR 0.68, 99.73% CI, 0.469–0.997; P=0.00251), with the median not reached (NR; 95% CI, 34.7 months–NR) and 28.7 months (95% CI, 22.9–NR), respectively. Durvalumab improved OS in all pre-specified subgroups. Updated PFS remained similar (stratified HR 0.51, 95% CI, 0.41–0.63), with medians of 17.2 and 5.6 months with durvalumab and placebo, respectively. Durvalumab improved the updated TTDM (stratified HR 0.53, 95% CI, 0.41–0.68), as well as PFS2 (stratified HR 0.58, 95% CI, 0.46–0.73), TFST (stratified HR 0.58, 95% CI, 0.47–0.72) and TSST (stratified HR 0.63, 95% CI, 0.50–0.79). Within the durvalumab and placebo groups, 30.5% and 26.1% had grade 3/4 any-causality AEs, 15.4% and 9.8% discontinued due to AEs, and no new safety signals were identified.
Durvalumab demonstrated statistically significant and clinically meaningful improvement in OS compared with placebo, supported by secondary endpoints such as PFS2. PACIFIC is the first study to show a survival advantage following CRT in this population, providing compelling evidence for the unprecedented benefit of durvalumab treatment as the standard of care.
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