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Barbara Melosky
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IS12 - Industry Symposium Sponsored by: Boehringer Ingelheim: Know Your Patients With NSCLC (ID 289)
- Event: WCLC 2020
- Type: Industry Symposium
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 1/30/2021, 13:00 - 14:00, Industry Symposia Auditorium (via Industry Hub)
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IS12.03 - Know How to Sequence EGFR TKIS (ID 4361)
13:00 - 14:00 | Presenting Author(s): Barbara Melosky
- Abstract
Abstract not provided
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P06 - Early Stage/Localized Disease - Multiple Primary Lung Cancer (ID 115)
- Event: WCLC 2020
- Type: Posters
- Track: Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P06.03 - Regression of the Ground Glass Component in Patients with Multifocal Primary Lung Cancers Receiving Pembrolizumab (ID 2078)
00:00 - 00:00 | Author(s): Barbara Melosky
- Abstract
Introduction
With the use of HRCT and lung cancer screening program, patients with multifocal primary lung cancers (MPLCs) are becoming a growing population in clinical practice worldwide. It's a rising challenging as no established treatment guideline. Having >= 1 Ground Glass nodule (GGN) or Part-Solid Nodule (PSN) suggests MPLC. Many of these GGN/PSN are pre-/early invasive, or preneoplastic, which is shown to have better preserved immune contexture, and therefore could benefit from immunotherapy (IO). This study is to evaluate potential beneficial effect of IO the pre-/early invasive adenocarcinoma in patients with MPLC.
Methods
We retrospectively reviewed CT in 13 stage IV NSCLC with MPLCs (9F: 4M, 70±4 yrs, 3CS vs. 10ES). All had tumor proportion score of PD-L1 ≥ 50% in dominant tumors and received first-line pembrolizumab. We evaluate disease response to pembrolizumab using RECIST 1.1 and the change of GGNs and PSNs (in addition to the dominant tumor) to pembrolizumab.
Results
27 GGNs/PSNs were found on 13 patients at baseline (16 GGN, Di: 13±6mm, 11 PSNs, Di entire nodule/solid core: 19±8/11±7mm). Over 267±196 days on pembrolizumab, 8 patients had radiographic partial response (PR) while 5 had progressive disease. 6 GGNs and 4 PSNs in 3/8 patients with PR improved: 3/6 GGNs (Di=7, 10, 12mm) have completely resolved and ther other 3/6 GGNs decreased (Di: from 9, 14, 21 to 3, 3, 7mm, Fig1); in 4 PSNs, their GGO component has completely resolved with only solid core at FU CT (Di entire nodule/solid core at baseline: 19±6/12±8mm; Di solid core at FU: 11±6mm, Fig2). The other 17/27 (10 GGNs and 7 PSNs) have unchanged/enlarged despite of similar baseline size to the regressed ones (GGNs: 13±6mm; PSNs: 20±10/10±6mm).
improved
Conclusion
Treatment with pembrolizumab resulted in the regression of the GGO component of the GGN and PSN. Further investigation of use of IO for patients with MPLC is warranted.
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P21 - Locoregional and Oligometastatic Disease - Treatment of Locally Advanced NSCLC (ID 131)
- Event: WCLC 2020
- Type: Posters
- Track: Locoregional and Oligometastatic Disease
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P21.05 - Overall Survival by PD-L1 Status in Stage III NSCLC Following Implementation of Durvalumab: The Real-World Application of PACIFIC (ID 1624)
00:00 - 00:00 | Author(s): Barbara Melosky
- Abstract
Introduction
In patients with unresectable stage III NSCLC, consolidative durvalumab has been shown to improve both PFS and OS following concurrent chemoradiotherapy. We performed a retrospective review to better understand patient outcomes by PD-L1 status in British Columbia.
Methods
A review of unresectable stage III NSCLC patients treated with chemoradiotherapy between March 2018 and June 2019 was conducted, after durvalumab was provincially available. Patient demographics, histology, stage, ECOG, smoking status, PD-L1 status if measured, sites of disease progression, and treatment toxicity were collected.
Results
196 patients were identified. Baseline characteristics were median age 67, female 49%, 69% non-squamous, 31% squamous histology. Median radiotherapy dose was 60 Gy, 38% received cisplatin, 62% carboplatin. 17% (n=34) PD-L1 <1%; 13% (n=25) PD-L1 1-49%; 23% (n=46) PD-L1 ≥50%; 46% (n=91) PD-L1 unknown. 49% (n=97) received durvalumab, with 47% (n=16) PD-L1 <1%; 36% (n=9) PD-L1 1-49%; 46% (n=21) PD-L1 ≥50%; 56% (n=51) PD-L1 unknown. Median time to starting durvalumab after chemoradiotherapy was 43 days, median treatment completed was 18 cycles, 22 patients remain on durvalumab. Within 6 weeks of completing concurrent chemoradiotherapy, 13% of patients progressed, 4% of patients died. Median follow-up was 18.2 months. Death on durvalumab vs surveillance was 29% vs 53% in PD-L1 <1%, 42% vs 63% in PD-L1 1-49%, 10% vs 42% in PD-L1≥50%, 17% vs 42% in PD-L1 unknown. The 1-year OS on durvalumab vs surveillance was 65% vs 47% in PD-L1 <1% (p=0.345), 53% vs 49% in PD-L1 1-49% (p=0.392), 95% vs 72% in PD-L1≥50% (p=0.039), and 88% vs 76% in PD-L1 unknown (p=0.023).
Conclusion
In a real-world population, durvalumab was associated with higher OS in patients with unresectable stage III NSCLC following concurrent chemoradiotherapy. There was a trend for improved overall survival in patients with high expression of PD-L1 (≥50%) from durvalumab after chemoradiotherapy, with 1-year OS 95% vs 72% (p=0.039). Durvalumab was not detrimental in patients with no expression or low expression of PD-L1, and further studies are needed to evaluate its benefit. Based on these findings, PD-L1 expression may be a useful biomarker to predict efficacy, and patients should not be excluded from receiving durvalumab after chemoradiotherapy based on PD-L1 status.
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P33 - Pathology - Immunotherapy Biomarker (ID 101)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P33.17 - Incidence of PD-L1 Expression at Clinically Significant Cut Offs in NSCLC EGFR Mutated Population Compared to Wild Type (ID 2710)
00:00 - 00:00 | Presenting Author(s): Barbara Melosky
- Abstract
Introduction
EGFR mutation can induce PD-L1 expression through p-ERK1/2/p-c-Jun pathway. The total incidence of PD-L1 positivity and percentage of PD-L1 immunoexpression at clinically significant cut off levels is not well studied. We performed a retrospective analysis of EGFR mutated NSCLC patients and correlated their tumors PD-L1 status. These results were compared to PD-L1 levels of NSCLC wild type patients.
Methods
In the province of British Columbia Canada, patients with advanced stage IIIB/IV NSCLC are tested for PD-L1 expression using the 22C3 PharmaDx kit. Cut off levels of <1%, 1-49% and >50% are reported, as per the pembrolizumab clinical trials. In British Columbia, mutational testing for activating mutations is performed after PD-L1 IHC, and therefore all patients with known EGFR mutation have a known PD-L1 status. A retrospective analysis was done to identify patients with advanced NSCLC who had PD-L1 testing between January 2017 and May 2018, and had EGFR testing results.
Results
174 patients were identified with tumors positive for an EGFR mutation. Baseline characteristics were median age 67, female 49%, 99% non-squamous and 1% squamous histology. Of the 174 tumors identified, 38% (n=66) were PD-L1 <1%; 36% (n=63) were PD-L1 1-49%; and 26% (n=45) were PD-L1 ≥50%. 771 patients were identified with EGFR wild type tumors. Baseline characteristics were median age 68, female 56%, 99% non-squamous and 1% squamous histology. Of the 771 tumors identified, 35% (n=266) were PD-L1 <1%; 22% (n=172) were PD-L1 1-49%; and 43% (n=333) were PD-L1 ≥50%. Fewer EGFR M+ samples compared to EGFR wildtype samples scored PD-L1 <50% (Chi-square statistic 17.76 p< 0.05) which was statistically significant.
Conclusion
Patients with tumors who are EGFR M+ have lower percentage of high PD-L1 > 50% expression (26% vs 43%) and higher percentage of no expression (38% vs 35%) than patients with wild type NSCLC. Significant fewer EGFR M+ samples compared to EGFR wildtype samples scored PD-L1 <50%. At present PD-L1 expression does not guide treatment decisions with immunotherapy in EGFR M+ patients, as single checkpoint inhibitors have shown little efficacy. The IMpower150 trial did show a signal in EGFR M+ tumors treated with atezolizumab, bevacizumab, carboplatin and paclitaxel. Future trials may show a role for measuring the PD-L1 expression level, and knowing the PD-L1 incidence by different cut off levels in the NSCLC EGFR mutant population may guide future clinical trial design.
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P37 - Pathology - Biomarker Testing (ID 107)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P37.17 - Prevalence of Epidermal Growth Factor Receptor (EGFR) Mutations in Non-small Cell Lung Cancer (NSCLC): A Global Meta-analysis (ID 3317)
00:00 - 00:00 | Presenting Author(s): Barbara Melosky
- Abstract
Introduction
Identification of variable EGFR gene mutations in NSCLC is increasingly important for the selection of appropriate targeted therapies. In this timely, global overview of EGFR mutated NSCLC we aim to address this clinical data gap.
Methods
Embase® and MEDLINE® in Ovid were searched for studies published 2004–2019 with cohorts of >50 adults with EGFR mutations, focusing on Stage III/IV NSCLC. Linear mixed-effects models were fitted to EGFR mutation endpoints using logistic transformation (logit), assuming a binomial distribution. The model included terms for an intercept reflecting European studies and further additive terms for other continents. EGFR sub-mutations examined were exon 21 L858R substitution, exon 19 deletion and ‘others’, with further analyses performed for exon 21 L858R substitution and exon 19 deletion.
Results
Of 3969 abstracts screened, 74 studies were included; 17 were considered non-representative of true prevalence in the wider NSCLC population (n=57 in overall model), but sub-mutation prevalence was assessed relative to the overall EGFR mutation population (n=74: Europe n=12; Asia n=51; North America n=5; Central America n=1; South America n=1; Oceania n=1; Global n=3). The final overall EGFR mutations model estimated a European prevalence of 12.8% (Table) and included an additive covariate for proportion of males in a study. There were no significant covariates in sub-mutation analyses. Most sub-mutations were actionable: exon 19 deletion (48.4% [Europe], 42.8% [North America], 49.2% [Asia]); exon 21 L858R substitution (29.9% [Europe], 29.8% [North America], 41.1% [Asia]).
Conclusion
Although EGFR mutation prevalence was higher in Asian than Western countries, data support testing overall and sub-mutations globally to inform appropriate targeted treatment decisions.
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P43 - Screening and Early Detection - Biomarkers (ID 178)
- Event: WCLC 2020
- Type: Posters
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P43.02 - A Multiplex Plasma Protein Panel for Detection of Lung Cancer in Ever Smokers Not Currently Eligible for Screening (ID 2407)
00:00 - 00:00 | Author(s): Barbara Melosky
- Abstract
Introduction
Lung cancer screening using low-dose computed tomography (LDCT) of the chest has been shown to reduce lung cancer mortality by 20% to 24% in heavy ever smokers. A sizeable proportion of light ever smokers do not meet screening criteria as defined by the US Preventive Services Task Force (USPSTF) for age, pack-years and quit-time. They furthermore do not meet the LDCT screening criteria set forth with the PLCOm2012 risk prediction model 6-year lung cancer risk threshold of ≥1.51%. To improve the impact of lung cancer screening programs, a simple low-cost risk-stratification method capable of identifying light ever smokers with similar lung cancer risk as heavy ever smokers is urgently needed. This study presents plasma protein assessment of informative biomarkers which may independently identify risk.
Methods
The study sample includes ever-smokers (55-80 years) with and without lung cancer who do not meet PLCOm2012 lung cancer risk model threshold of ≥1.51%/6-years or the USPSTF criteria (≥30 pack-years and smoked within the past 15 years). Plasma samples from individuals who were not eligible for the International Lung Screening Trial (ILST) and light ever smokers with Stage I lung cancer prior to surgical resection were subject to multiplex assay for Pro-surfactant protein B (ProSB) and Carcinoembryonic antigen (CEA) using the MagArray magnetic nanosensor. The results were compared to ILST participants with or without lung cancer with PLCOm2012 risk score >1.5%.
Results
The characteristics of the subjects studied are shown in Table 1.
Among the light ever smokers with a PLCOm2012 risk score <1.5%, a significantly higher level of ProSB was observed in those with lung cancer compared to the non-cancer controls (P=0.001) ProSB levels are similar between cancer subjects irrespective of the PLCOm2012 risk score but were significantly lower in the non-cancer subjects with a PLCOm2012 risk score <1.5% versus those with a PLCOm2012 risk score >1.5%. CEA was higher in the cancer versus non-cancer subjects although not statistically significant in those with a PLCOm2012 risk score <1.5% (P=0.09).
Conclusion
Using a blood biomarker such as ProSB may identify light ever smokers who do not meet current eligibility criteria for screening but may benefit from LDCT screening.
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P89 - Targeted Therapy - Clinically Focused - Translational (ID 266)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P89.03 - Demonstrating VALUE of Liquid Biopsy for Lung Cancer in a Public Healthcare System (ID 2333)
00:00 - 00:00 | Author(s): Barbara Melosky
- Abstract
Introduction
Liquid biopsy (LB) is an important alternative for advanced lung cancer patients in diagnosing resistance or where tissue genotyping has failed. The VALUE study examines clinical outcomes and utility of LB for molecular diagnosis in treatment naive stage IV lung adenocarcinoma patients.
[Preliminary data previously presented at ASCO2020. Final study results will be available for WCLC2021]
Methods
This study is being conducted at 6 Canadian centres (NCT03576937) using Guardant360TM (G360), a validated cell-free DNA next-generation sequencing assay that identifies variants in 74 cancer-associated genes, including fusions and copy number gain. Patients with treatment-naïve advanced non-squamous lung carcinoma, ≤10 pack-year smoking history, and measurable disease are eligible (N=150). Patients receive standard of care tumour tissue (TT) molecular profiling (EGFR, ALK +/- ROS1) and LB. The primary endpoint is response rate to first-line therapy (RECIST 1.1); secondary endpoints include incremental targetable alterations identified through G360 (EGFR, ALK, BRAF, ERBB2, KRAS (G12C), NTRK, MET (amplification, exon 14 skipping), RET, ROS1), turnaround time (TAT) and successful molecular profiling rates.
Results
To date, 150 eligible patients have been enrolled. Demographic data are available for the first 100 patients, treatment data for 89 and 60 have response data. Median age is 63 (range 22-91), 63% are female, 85% never smokers, 35% East Asian, 24% ECOG PS>1, and 94% have adenocarcinoma. Actionable targets have been identified in 55% of patients using G360 (EGFR/ALK in 38%), and 38% using standard TT profiling. Concordance between TT and LB was high, 84%, with 8 cases each identified by TT or LB but not the other. TT profiling for EGFR/ALK was unsuccessful in 6% of patients (insufficient tissue, failed biopsy, single biomarker tested only). Fifteen patients (15%) had no ctDNA alterations detected by G360 (low disease burden vs. non-shedding). Of 89 patients receiving first-line treatment, 60% received targeted therapy, 26% chemo-immunotherapy combinations, 10% checkpoint inhibitors alone and 4% were observed. Treatment decisions were informed by G360 alone in 40% and by G360+TT results in 28% (by physician report). Among 51 evaluable patients, ORR was 55% (28/51). Using G360, ORR was 75% (18/24) in those with actionable alterations and 37% (10/27) in those without. Using TT, ORR was 64% (16/25) in those with actionable alterations and 46% (12/26) in those without. Mean TAT was 7.7 days (SD+/-1.6) for LB vs 20.8 days (SD+/- 9.8) for TT.
Conclusion
LB using G360 identifies actionable targets beyond tissue profiling alone in newly diagnosed lung cancer patients, has faster TAT and yields similar outcomes with targeted and non-targeted therapy.
