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Tracy Li
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MA04 - Health Policy and the Real World (ID 217)
- Event: WCLC 2020
- Type: Mini Oral
- Track: Health Services Research/Health Economics
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 16:45 - 17:45, Scientific Program Auditorium
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MA04.07 - Comparative Clinical Outcomes for Patients with NSCLC Harboring EGFR Exon 20 Insertion Mutations and Common EGFR Mutations (ID 3390)
16:45 - 17:45 | Author(s): Tracy Li
- Abstract
- Presentation
Introduction
Approximately 85–90% of the mutations seen in EGFR-mutant non-small cell lung cancers (NSCLCs) are common mutations (cEGFR), Exon 19 deletions and Exon 21 L858R. Up to 10% of EGFR-mutant NSCLC harbors Exon 20 insertion mutations (Exon20ins). We conducted a retrospective cohort study using real-world data to compare clinical outcomes between patients harboring Exon20ins and cEGFR.
Methods
This retrospective cohort study included patients from the Flatiron Health database (1 January 2011 through 31 May 2020) who had advanced NSCLC. The objectives of the study were to assess the prognostic value of Exon20ins compared with cEGFR (start date of first-line therapy as the index date) and the effect of tyrosine kinase inhibitor (TKI) treatment between the groups (start date of first TKI line as the index date). Analysis was stratified by line of TKI use. Endpoints included real-world overall survival (rwOS), progression-free survival (rwPFS), and time to next therapy (rwTTNT) and were analyzed using multivariable Cox proportional hazards model and summarized by Kaplan-Meier method.
Results
Among 62,464 patients with advanced NSCLC, 181 with Exon20ins and 2833 with cEGFR met eligibility criteria. Population demographics between the groups were comparable with minor exceptions. With median 34-month follow-up, Exon20ins was associated with a 75% increased risk of death (adjusted hazard ratio [adjHR] of 1.75 [95%CI, 1.45–2.13]; p˂0.0001); median rwOS was 16.23 (95%CI, 11.04–19.38) for Exon20ins and 25.49 months (95%CI, 24.48–27.04) for cEGFR (Table). The estimated 5-year survival rate for Exon20ins is 8% compared with 19% for cEGFR.
The predictive value of TKI treatment, stratified by line, was assessed in 76 Exon20ins and 2749 cEGFR patients who were treated with TKIs. With median 20.6-month follow-up, there was a 170% increase in risk of progression or death associated with Exon20ins (adjHR of 2.7 [95% CI, 2.06–3.55]; p˂0.0001); median rwPFS was 2.86 months (95%CI, 2.14–3.91) compared with 10.45 months (95%CI: 10.05–10.94) for cEGFR. Furthermore, there was a 170% increased risk of death (adjHR of 2.70 [95% CI, 2.04–3.57]; p˂0.0001) associated with Exon20ins; median rwOS was 7.46 months (95%CI, 5.45–13.34) for Exon20ins and 25.49 months (95%CI, 24.28–26.81) for cEGFR (Table).
Conclusion
Patients with Exon20ins have a worse prognosis compared with patients with cEGFR. Furthermore, EGFR TKI treatment was substantially less effective for patients with Exon20ins, as the risk of disease progression and mortality was higher compared with patients with cEGFR. These findings highlight the need for new treatment options for Exon20ins.
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P09 - Health Services Research/Health Economics - Real World Outcomes (ID 121)
- Event: WCLC 2020
- Type: Posters
- Track: Health Services Research/Health Economics
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P09.61 - Epidemiological and Clinical Burden of EGFR Exon 20 Insertion in Advanced NSCLC: Results of a Systematic Literature Review (ID 1271)
00:00 - 00:00 | Presenting Author(s): Tracy Li
- Abstract
Introduction
The burden of epidermal growth factor receptor (EGFR) exon 20 insertion (ex20Ins) mutation is not well understood. A systematic review was conducted to identify the available evidence on mutation frequency, prognostic impact, and clinical, patient-reported, and economic outcomes.
Methods
Prespecified PICOS criteria were used to determine study eligibility. MEDLINE, Embase (1974-September 2019), and conference proceedings (2018-2019) were searched. Studies were not limited by intervention, geography, or publication year and were stratified by line of therapy.
Results
Eighty-four unique studies were included; 53 reporting mutation frequency, 18 prognostic impact, 35 clinical outcomes, and one humanistic burden. No economic burden data were identified.
The frequency of ex20Ins mutation ranged from 0.1% to 4% of all NSCLC cases and 1% to 12% of all EGFR mutations with a wide range of test methodologies observed (Table 1). Data on the prognostic impact of ex20Ins were heterogeneous but highlighted poorer treatment outcomes in ex20Ins compared with other EGFR mutations and EGFR wildtype across a wide range of therapies (chemotherapy, TKIs) and treatment lines.
Seven clinical trials and 37 prospective observational studies reported clinical outcomes for patients with ex20Ins (Table 2). Trends towards better median PFS, OS, and ORR were observed for chemotherapy compared with TKIs as first-line treatments. For subsequent treatment lines, novel targeted therapies provided encouraging preliminary responses while results for chemotherapy were limited. Limited safety data were reported.
One conference abstract described the symptom burden for ex20Ins patients with fatigue and pain being most common.
Conclusion
We found substantial global variations in the frequency of ex20Ins mutation detection. Across the clinical studies, ex20Ins had a worse prognosis compared to common EGFR mutations. Data on emerging ex20Ins targeted therapies are encouraging but limited. More research is needed to understand the humanistic and economic impact of ex20Ins.
Table 1. The Range of Mutation Frequency Reported Across the Included Studies by Region Region
Frequency of exon 20 ins (%)
# Studies
NSCLC
# Studies
EGFRm Positive NSCLC
US
9
0.5-2.6%
7
5-12%
Latin America
7
1.3-2.1%
5
5-8%
Europe
13
0.3-1.3%
10
4-12%
Asia Pacific
28
0.1-4.0%
16
1-5%
China
9
0.3-2.9%
7
2-5%
Japan
4
1.8-2.4%
2
2-5%
Taiwan
3
1.3-4.0%
2
3-4%
South
5
0.3-3.4%
4
1-4%
South East
4
0.1-2.4%
2
2-3%
Australia
1
1.4%
0
NA
Table 2. Range of Ex20Ins Clinical Outcomes Across Included Studies: Mean OS and PFS (months) and ORR (%) by Line of Therapy and Treatment Type For Treatment Groups Including >10 Patients 1L
2L+
Mixed LOT
All Treatments
mOS
6.3-28
[10 studies; 307 patients]8-17.1
[6 studies; 129 patients]4.8-29.4
[7 studies; 235 patients]mPFS
1.8-6.9
[11 studies; 354 patients1.9-7.3
[10 studies; 215 patients]1.4-4.5
[8 studies; 203 patients]ORR
0-29%
[7 studies; 250 patients]0-43%
[12 studies; 374 patients]0-67%
[9 studies; 218 patients]TKI
mOS
7.1-16.8
[4 studies; 81 patients]12.9-15.3
[2 studies; 47 patients]4.8-19
[4 studies; 125 patients]mPFS
1.8-6.4
[6 studies; 116 patients]1.9-3.7
[4 studies; 79 patients]1.4-3.1
[7 studies; 206 patients]ORR
6.3-8.7%
[2 studies; 39 patients]0-43%
[5 studies; 107 patients]0-36%
[6 studies; 142 patients]Chemotherapy
mOS
15.9-28
[4 studies; 259 patients]17.1
[1 study; 17 patients]26-29.4
[3 studies; 113 patients]mPFS
3.4-6.9
[5 studies; 238 patients]4.1-4.8
[3 studies; 58 patients]4.5
[1 study; 22 patients]ORR
23-29%
[4 studies; 211 patients]17-42%
[2 studies; 24 patients]50-63%
[3 studies; 79 patients]Ex20Ins Targeting Therapy
mOS
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mPFS
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7.3
[1 study; 28 patients]-
ORR
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14.8-43%
[4 studies; 214 patients]-
