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Narumol Trachu
Author of
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-78 - PD-L1 Expression as a Prognostic Marker for Non-Small Cell Lung Cancer in Distinct Mutational Status (ID 2927)
10:15 - 18:15 | Presenting Author(s): Narumol Trachu
- Abstract
Background
Programmed death-ligand 1 (PD-L1) expression is widely used as the predictive biomarker for immunotherapy treatment in NSCLC whereas their role as a prognostic marker is limited.
Method
Seventy-nine FFPE tissues (stage I-IV) during 2012-2017 were retrieved for Next Generation Sequencing (NGS) and immunohistochemistry (IHC) staining. PD-L1 expression was performed using 22C3 Ab. Positive-PD-L1 was defined by tumor proportion score (TPS) >1%. Targeted mutations and fusion genes were analyzed by Lung Cancer Panel 45 Genes and Targeted RNAscan Panel on NGS, respectively. Variants from NGS with coverage of higher than 1000X, cutoff ≥3% alternate variant frequency were considered positive. The cutoff was validated by Real-time PCR. Clinical data correlation was analyzed.
Result
Thirty-one patients (39%) had stage I-II and 48 patients (61%) had stage III-IV disease. Mean age was 62.5 years old. Fifty-one patients (65%) were female and 55 patients (70%) were never-smoker. A majority of the patients (83.6%) were negative-PD-L1. All of the 13 PD-L1 positive patients were in stage III-IV, suggesting the increased likelihood of PD-L1 expression in advanced disease (p = 0.014). No difference in age, sex, smoking status, histological subtypes, and mutational status were seen between PD-L1 positive and negative group.However, PD-L1 negative was associated with a trend toward better survival (Table1). Subgroup analysis in stage IV patients with common EGFR mutations revealed PD-L1 positive status as a significant negative prognostic factor with HR of 3.00 (95% CI: 1.17, 7.73; P-value=0.023), whereas positive-PD-L1 patients with the other mutations showed a trend of worse survival outcome.
Table 1: Cox regression analysis of prognostic factors associated with overall survival of NSCLC patients
ConclusionPrognostic factors
Follow up time
(100 person-month)
Death
Median survival
(mo)
Univariate analysis
Multivariate analysis
No.
Rate (95% CI)
HR (95% CI)
p-value
Adjusted HR (95% CI)
p-value
Age
1.00 (0.98, 1.03)
0.893
-
Sex
0.250
Male
8.71
18
2.07 (1.30, 3.28)
22.8
1.43 (0.79, 2.59)
0.243
-
Female
21.14
28
1.32 (0.91, 1.92)
53.9
1
-
PDL1
0.002
Negative (<1%)
28.05
35
1.25 (0.90, 1.74)
53.9
1
1
Positive (≥1%)
1.80
11
6.09 (3.38, 11.00)
7.1
3.52 (1.73, 7.16)
0.001
1.88 (0.83, 4.22)
0.128
Stage
<0.001
I-II
19.20
6
0.31 (0.14, 0.70)
NR
1
1
III-IV
10.65
40
3.76 (2.75, 5.12)
20.1
11.09 (4.26, 28.87)
<0.001
10.03 (3.67, 27.41)
<0.001
Smoking status
0.011
Never smoker
24.04
28
1.16 (0.80, 1.69)
76.2
1
1
Ex-smoker
4.55
10
2.20 (1.18, 4.09)
20.1
1.70 (0.82, 3.52)
0.154
1.02 (0.47, 2.23)
0.962
Current smoker
1.26
8
6.33 (3.17, 12.66)
8.7
3.76 (1.68, 8.41)
0.001
1.70 (0.74, 3.88)
0.208
EGFR
0.825
Mutation
22.99
35
1.52 (1.09, 2.12)
31.9
0.93 (0.47, 1.83)
0.824
-
No mutation
6.87
11
1.60 (0.89, 2.89)
33.5
1
-
ALK
0.869
Positive
2.28
3
1.32 (0.43, 4.09)
NR
1.11 (0.33, 3.78)
0.867
-
Negative
16.50
19
1.15 (0.73, 1.81)
76.2
1
-
KRAS
0.051
Mutation
13.12
12
0.91 (0.52, 1.61)
NR
0.53 (0.27, 1.03)
0.062
-
No mutation
16.73
34
2.03 (1.45, 2.84)
31.1
1
-
Number of co-MT
0.045
< 1000
11.84
27
2.28 (1.56, 3.33)
22.8
1
1
≥ 1000
18.02
19
1.05 (0.67, 1.65)
57.6
0.55 (0.30, 0.99)
0.047
1.22 (0.61, 2.41)
0.574
Positive-PD-L1 is significantly associated with advanced disease and a trend toward unfavorable prognosis. The detrimental effect of PD-L1 is significant in stage IV patients with common EGFR mutations. A confirmatory study with a larger sample size would better identify the prognostic benefit of PD-L1 status in vast subsets.
