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Young Kwang Chae
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EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.01-94 - The Role of Neoadjuvant Chemo-Immunotherapy in Unresectable Non-Small Cell Lung Cancer (Now Available) (ID 2873)
08:00 - 18:00 | Presenting Author(s): Young Kwang Chae
- Abstract
Background
Current practices and guidelines invoke a limited role for neoadjuvant therapies in NSCLC. These strategies are not considered for use in advanced, unresectable disease. However, the development of immune checkpoint inhibitors has drastically improved the efficacy of systemic treatments for NSCLC.
Method
We describe the case of a patient who was diagnosed with squamous cell carcinoma of the lung.
Result
Imaging demonstrated a 7.9-cm right lower lobe lesion, a 1.8-cm satellite right middle lobe nodule, and ipsilateral mediastinal lymphadenopathy, consistent with stage IIIB disease. The tumor biopsy exhibited 5% PD-L1 positivity in tumor cells. Tissue next generation sequencing (NGS) revealed loss-of-function mutations in RB1, TP53, and EP300, copy number gain in PIK3CA, and tumor mutational burden of 4.3/Mb. Analysis of circulating tumor DNA (ctDNA) demonstrated a highest allele fraction of 4.1% (TP53 mutant clone). As the tumor was deemed unresectable, the patient was started on carboplatin, nab-paclitaxel, and pembrolizumab. Follow-up imaging at 12 weeks after 4 cycles showed partial response, with significant reduction in tumor size and improvement in lymphadenopathy. After tumor board discussion, the decision was made to proceed with surgical resection. A right thoracotomy with bilobectomy was successfully performed. Resected tumor demonstrated major pathologic response with less than 5% viable cancer cells. Whole-genome sequencing of plasma was also carried out on blood collected over the course of treatment. The observable cancer signal shrank to less than 5% of the baseline as early as 25 days after treatment start. Finally, repeat ctDNA analysis 6 weeks after the surgery showed no detectable somatic variants.
Conclusion
Conversion of unresectable tumors in NSCLC may be more feasible with modern treatment regimens. The potential efficacy of neoadjuvant strategies using chemoimmunotherapy warrants further clinical investigation.
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EP1.04 - Immuno-oncology (ID 194)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.04-12 - Response to Combination of Metformin and Nivolumab in a NSCLC Patient Whose Disease Previously Progressed on Nivolumab (Now Available) (ID 2899)
08:00 - 18:00 | Presenting Author(s): Young Kwang Chae
- Abstract
Background
Beyond metformin’s success as a widely used anti-diabetic, there is mounting evidence for its anti-cancer properties. Metformin disrupts many molecular pathways, in particular causing mTOR inhibition. Additionally, it causes metabolic alterations that might impact cancer cell survival. Recent experiments have also suggested that metformin has immune modulatory properties. Metformin impairs immunologic exhaustion of CD8+ lymphocytes, potentiating immune response to tumors. Thus, when curbing acquired resistance to immune checkpoint inhibition, adding metformin could prove to be a valid strategy. Here, we present a case of a NSCLC patient for whom the addition of metformin coincided with reversal of disease progression on a single-agent nivolumab.
Method
This is a case report obtained by medical records revision.
Result
Case report: A 75-year-old male, ex-smoker, initially presented with symptomatic left pleural effusion and multiple lung nodules 7 years ago. Pathology confirmed poorly differentiated adenocarcinoma, wild-type for molecular targets. Disease was Stage IV based on the presence of a malignant pleural infusion. The patient underwent VATS and left pleurodesis and was started on systemic therapy. After four cycles of pemetrexed-platinum doublet, he was put on maintenance chemotherapy with clinical response but, eventually, maintenance treatment was discontinued due to worsening fatigue. The patient developed significant disease progression resulting in a left peripheral mass adjacent to the cardiac silhouette. He then underwent localized SBRT followed by disease stability for approximately 6 months. 48 months ago, the patient developed progressive disease and was briefly put on vinorelbine. Due to toxicity and worsening kidney function, the treatment was stopped after one cycle. One month later, the patient started the immune checkpoint inhibitor, nivolumab. In the first imaging assessment there was evidence of response to immunotherapy and that was followed by disease control for 10 months. After that, asymptomatic lung and pleural progression ensued. Initial decision was made to continue nivolumab. Repeat scans revealed continued interval increases in the lung nodules. Metformin XR 2000mg PO daily was added to the treatment regimen. Since then, the patient has been tolerating the combination treatment well and new response was observed in the following scans with interval diminishing of the lung nodules followed by on-going stability for 17 months.
Conclusion
There has been some evidence that metformin can enhance anti-PD-1/PD-L1 activity. We here presented a case of metastatic lung adenocarcinoma with long-term disease stability coinciding with the addition of metformin to nivolumab regimen. A new phase-2 clinical trial (NU16L04) open in our institution has been accruing NSCLC patients, including those previously refractory to anti-PD-1/PD-L1 to receive nivolumab and metformin combination.
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-49 - Serial Changes in Whole-Genome Cell-Free DNA (cfDNA) to Identify Disease Progression Prior to Imaging in Advanced NSCLC (ID 2484)
09:45 - 18:00 | Presenting Author(s): Young Kwang Chae
- Abstract
Background
Response to treatment in advanced lung cancer is usually determined by clinical and imaging assessment. We analyzed longitudinal changes in blood whole-genome cfDNA to investigate whether a molecular response assessment could provide potentially actionable information prior to imaging.
Method
We prospectively enrolled and serially collected blood from 35 patients with advanced non-small cell lung cancer (NSCLC). Baseline blood samples were drawn prior to initiation of a new treatment and at one or two additional time points, after the first cycle (median 21 days) and the second cycle (median 42 days). 4 mL of plasma was separated from peripheral blood collected in Streck tubes. Next, cfDNA was isolated from plasma and used to prepare libraries (15 with bisulfite conversion) for whole-genome sequencing at approximately 20X depth. Based on a patient-specific profile of whole-genome features, changes in the fraction of tumor-derived cfDNA were quantified over the initial course of treatment. Imaging was performed per standard practice with treatment response determined by an independent radiologist according to RECIST guidelines.
Result
Median age of patients was 72 (range 48-87), and 49% were female. 69% of patients were on their first line of therapy (range 1-5). Patients were treated with an immune checkpoint inhibitor +/- chemotherapy (22), chemotherapy alone (11), or targeted therapy (2). Patients with predicted progression by cfDNA (n=4), indicated by an increase in tumor fraction at either post-treatment blood collection, had worse progression-free survival (PFS) compared to patients who did not show an increase (n=31) (hazard ratio 22.3, [95% CI 3.9-127.8], log-rank p=9 x 10-7). For the patients who were predicted to progress, the cfDNA assay preceded clinical evaluation by a median of 34 days. Median PFS was 56 days for patients with predicted progression versus 370 days for others. All patients with predicted progression were later confirmed to progress at the first follow-up evaluation (4/4, 100% positive predictive value). For the remaining patients, 27 of 31 did not progress (87% negative predictive value). Therefore, sensitivity for the assay was 50% and specificity was 100%.
Conclusion
Analyzing tumor-derived cfDNA early in the course of a new therapy holds promise to identify patients with early disease progression across multiple types of treatment. This technology may enable early switching to other potentially effective therapies, increasing the value proposition of all delivered treatment.
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P1.01-67 - Ph I/II Carboplatin, Nab-Paclitaxel and Pembrolizumab for Advanced NSCLC (HCRN LUN13-175): Outcomes by Nab-Paclitaxel Dose (ID 530)
09:45 - 18:00 | Author(s): Young Kwang Chae
- Abstract
Background
Combination chemotherapy and immunotherapy have significantly improved survival for patients with treatment-naïve advanced non-small cell lung cancer (NSCLC). We sought to evaluate the safety and efficacy of adding pembrolizumab to a standard regimen at the time of study development, nab-paclitaxel and carboplatin. Safety data from phase I have been reported, and phase II commenced with the same chemotherapy doses and flat dosing of pembrolizumab at 200 mg.
Method
Patients with treatment-naïve, stage IIIB/IV NSCLC AJCC 7 (all histology), any PDL1, no EGFR or ALK, ECOG 0-1, received carboplatin AUC 6 day 1, nab-paclitaxel 100 mg/m2 days 1, 8, 15, and pembrolizumab 200 mg day 1 q21 days for 4 cycles followed by maintenance pembrolizumab q3wks. Co-primary endpoints were progression-free survival (PFS) and response rate (RR). PDL1 was assessed prior to treatment and from biopsies obtained after cycle 4.
Result
46 patients enrolled, 14 on phase I and 32 in phase II, from June 2015–July 2018. Accrual stopped after data was presented from similar phase III trials. 43 were evaluable for the primary endpoints. Median age was 65 years, 48% female, 45% adenocarcinoma, 94% current/former smokers, 9% brain metastases. PDL1 expression (TPS) by <1%, 1-49%, and ≥ 50% cutoffs was 44%, 28%, and 28%, respectively. ORR was 28%. Median PFS was 5.6 months (CI, 4.2-10.5 mo). Median OS was 15.7 mo (CI 11.1-22.3 mo). There was no statistical differences in PFS or OS outcomes by PDL1 status. Paired PDL1 results from pre- and post-treatment biopsies were available in 8 patients. PDL1 status changed categories in 4/8 samples (n=3, 0% to positive; n=1, 99% to 0%). The most common grade 3-4 adverse events (AEs) were neutropenia (64%), anemia (31%), thrombocytopenia (24%), leukopenia (16%) and fatigue (11%). Other notable AEs included rash (58%), diarrhea (47%), neuropathy (22%), arthralgia (18%), transaminitis (13%), and myalgia (11%). 18% discontinued treatment due to AEs. In an exploratory analysis, there was no difference in median PFS for those receiving total nab-paclitaxel dose of 400–799 mg/m2 compared to ≥800 mg/m2 (6.2 mo vs. 8.2 mo, p=0.62).
Conclusion
Although the study did not meet its pre-specified endpoints of PFS 9 months and RR of 50%, results were similar to previously reported phase III Keynote 407 (squamous histology). Despite hematologic toxicity, the combination could safely be administered, and outcomes were similar for those receiving moderate doses of nab-paclitaxel compared to those with an average of at least 200 mg/m2 per cycle.
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P1.03 - Biology (ID 161)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.03-38 - EGFR Mutation Status as a Prognostic Marker in Stage 1 Lung Adenocarcinoma After Definitive Surgical Resection (Now Available) (ID 646)
09:45 - 18:00 | Author(s): Young Kwang Chae
- Abstract
Background
With tumor molecular genetics at the forefront of precision medicine, EGFR mutation status has been paramount for predicting response to therapy in advanced and metastatic NSCLC. However, little is known about the implications of EGFR mutation status in stage 1 disease following definitive surgical therapy, particularly in regard to prognosis and disease recurrence.
Method
We retrospectively studied the clinical outcomes in 101 EGFR-positive patients and 97 age-matched EGFR-negative controls with stage 1 lung adenocarcinoma who underwent definitive surgical resection +/- chemoradiation. EGFR status was determined by pathologic molecular testing performed at time of diagnosis and TNM stage was determined at time of treatment. These cases were then followed for pathologically confirmed cases of recurrence and assessed for stage at recurrence, time elapsed since definitive treatment, and disease-free survival at 1, 2 and 5 years.
Result
EGFR-positive disease demonstrated higher rates of metastatic recurrence with 15% vs 3% in controls (p=0.007). Median time to progression among those who progressed, defined as time to recurrence or death, was significantly shorter in EGFR-positive cases (82 weeks vs 158 weeks, p=0.048). There was no significant difference in rates of recurrence (p=0.32) between both groups. Disease-free survival in EGFR-positive cases was most notably lower at 2 years, with 0.86 (0.78-0.94) vs 0.94 (0.89-0.99).
Conclusion
This study suggests that EGFR-positive disease may be associated with a higher risk of metastatic recurrence and decreased time to progression in individuals who ultimately progress. EGFR molecular testing may be a promising tool for risk stratification and surveillance following definitive management for stage 1 disease. Future prospective modeling may be indicated in this disease.
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P1.17 - Treatment of Early Stage/Localized Disease (ID 188)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.17-40 - Clinical Implications of Using Circulating Tumor DNA to Assess Minimal Residual Disease (MRD) in Patients with NSCLC After Definitive Treatment (ID 1801)
09:45 - 18:00 | Author(s): Young Kwang Chae
- Abstract
Background
Circulating tumor DNA (ctDNA) has been used to identify driver genomic alterations during treatment of metastatic nonsmall cell lung cancer (NSCLC). Recent studies have also demonstrated the role of ctDNA to monitor response to therapy. Here we performed an analysis on a cohort of NSCLC patients (pts) with localized disease who underwent ctDNA testing after definitive treatments to determine whether ctDNA can be used as a marker of MRD.
Method
Between 2015-2019, 70 pts with localized NSCLC received ctDNA testing. ctDNA testing was done using the next generation sequencing (NGS) panel of 73 genes via digital sequencing technology (Guardant360). Statistical analysis was performed to determine which factors were associated with ctDNA levels and recurrence free survival (RFS).
Result
Of the 70 pts analyzed, 26 pts had ctDNA testing performed after definitive treatment. Median duration of follow up was 22 months (range: 3 to 36). 26% (n = 7) had stage I disease, 30% (n = 8) had stage II disease, and 42% (n = 11) had stage III disease. 81% (n = 21) were adenocarcinoma while 19% (n = 5) were squamous cell carcinoma. 42% (n = 11) had no recurrence during our observation time, while 58% (n = 15) experienced progression. For definitive treatments, 38% (n = 10) underwent surgery alone, 35% (n = 9) underwent surgery with adjuvant chemotherapy, 15% (n = 4) underwent chemoradiation therapy, 8% (n=2) underwent surgery followed by radiation, and 4% (n=1) under went surgery with adjuvant chemoradiation prior to their ctDNA levels [variant allele frequency (VAF)] being drawn. Of these, 15% (n = 4) tested negative for any ctDNA, while 85% (n = 22) were positive. Only one of the pts with undetectable levels of ctDNA experienced recurrence of cancer 34 months after definitive treatment with surgery followed by chemotherapy. 13 among 22 pts with detectable ctDNA had recurrence (median time to recurrence = 6.3 months). Kaplan-Meir survival analysis revealed a trend toward significant association between the presence of detectable ctDNA and RFS (p = 0.10).
Conclusion
Our analysis demonstrates that ctDNA could potentially be used as a marker to assess MRD following definitive treatment for localized NSCLC.
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P2.11 - Screening and Early Detection (ID 178)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Screening and Early Detection
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.11-06 - Serum Proteomic Signature as a Potential Biomarker for Survival in Patients with NSCLC Receiving Immunotherapy (Now Available) (ID 86)
10:15 - 18:15 | Author(s): Young Kwang Chae
- Abstract
Background
The VeriStrat Test is a serum assay which uses a mass spectrometry (MS)-based proteomic signature derived from machine learning. It is currently used as a prognostic marker for patients with NSCLC receiving chemotherapy. However, little is known about its role for NSCLC patients receiving immune checkpoint inhibitors (ICIs).
Method
This is a retrospective study that includes 47 patients with advanced stage NSCLC without an activating EGFR mutation, who underwent the VeriStrat Test from 2016 to 2018. Spectra from blood samples were evaluated to assign patients into the VeriStrat ‘Good’ (VS-G) or VeriStrat ‘Poor’ (VS-P) risk group. The clinical outcomes of 32 patients who received programmed cell death 1(PD-1) inhibitors nivolumab or pembrolizumab were analyzed by the VeriStrat status.
Result
The VS-G group demonstrated significantly higher progression-free survival (PFS) and overall survival (OS) compared to the VS-P group among overall NSCLC patients regardless of treatment (median PFS of 7.1 vs. 4.2 months, p=0.013, and median OS, not reached vs. 17.2 months, p=0.012). Among NSCLC patients treated with ICIs, VS-G classification was associated with significantly increased PFS in comparison to VS-P classification (median PFS of 6.2 vs. 3.0 months, p=0.012), while the differences in OS trended towards significance (median OS, not reached vs. 16.5 months, p=0.076). Multivariate analyses showed that the VeriStrat status had a borderline significance (p=0.051) in predicting PFS in NSCLC patients treated with ICIs.
Conclusion
MS-based serum proteomic signature has a potential as a biomarker for survival outcome in NSCLC patients receiving immunotherapy.
