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Sorrapong Manyanont
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FP07 - Pathology (ID 109)
- Event: WCLC 2020
- Type: Posters (Featured)
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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FP07.13 - Clinical Characteristics and Outcomes in Patients With KRAS G12C Mutated Non-Small Cell Lung Cancer (ID 1415)
00:00 - 00:00 | Author(s): Sorrapong Manyanont
- Abstract
Introduction
KRAS oncogenic mutations are the most common driver alterations in non-small cell lung cancer (NSCLC). Among these, G12C mutations are the most frequently encountered and targetable with currently available investigational therapies. Understanding the clinical characteristics and outcomes in patients with G12C mutated NSCLC has the potential to inform clinical testing in resource limited settings and facilitate the study of novel combination therapies.
Methods
KRAS-mutant NSCLC patients treated at Washington University in St. Louis were retrospectively identified through review of commercial target hybrid-capture next generation sequencing (NGS) test results (plasma and tissue). Clinical and demographic information was collected from electronic medical records. Patients were categorized into two groups based on the KRAS mutation: G12C and non-G12C. Fisher’s exact test was used for comparing categorical variables and log-rank test was used to test for differences in survival, between these categories.
Results
A total of 169 patients with KRAS mutations were identified for this study. Nearly a third of patients were G12C mutated (n=64,37.6%) (Table 1). The majority of patients in both groups were diagnosed with stage IV disease (68.7% [G12C] and 72.9% [non-G12C]). PD-L1 (22C3 antibody) status was available in 43.7% of patients and PD-L1 status did not significantly differ between both categories (p=0.772). G12C mutations were observed in patients of all races and predominantly in smokers (96.9%). Apart from adenocarcinomas (92.2%), G12C mutations were also observed in large cell carcinomas (n=5), poorly differentiated carcinomas (n=3), NSCLC-NOS (n=1) and combined adenocarcinoma-small cell lung cancer (n=1). Pattern of metastasis at presentation did not differ between G12C and non-G12C patients. Overall, 28 KRAS mutated patients received immunotherapy as single agent or in combination with chemotherapy in the first-line setting (n=10 [G12C] and n=18 [non-G12C]). While no statistically significant difference in PFS and OS were found between these categories (median PFS 6.24 [G12C] vs 6.27 months [non-G12C], log rank p=0.899; median OS 21.0 [G12C] vs 21.8 months [non-G12C], log rank p=0.992), G12C mutated NSCLC was associated with a better PFS than non-G12C NSCLC (p=0.0384), when the analysis was restricted to patients achieving a durable response to immunotherapy (PFS>3.5 months, corresponding to first 4 cycles).
ConclusionTABLE 1. Patients Characteristics
Characteristic
KRAS G12C (n=64)
Non-KRAS G12C (n=105)
p-valuea
Median Age (range)
64.5 (47-89)
63.0 (46-89)
Gender, n (%)
0.626
Male
22 (34.4)
40 (38.1)
Female
42 (65.6)
65 (61.9)
Race, n (%)
0.156
Caucasian
54 (84.4)
82 (78.1)
African American
7 (10.9)
22 (21.0)
Asian
2 (3.1)
1 (1.0)
Hispanic
1 (1.6)
0 (0)
Smoking history, n (%)
0.08
Ever
62 (96.9)
94 (89.5)
Never
2 (3.1)
11 (10.5)
Histology, n (%)
0.146
Adenocarcinoma
59 (92.2)
83 (77.6)
Squamous cell
0 (0)
6 (5.6)
Large cell
5 (8.0)
18 (16.8)
NSCLC-NOS
3 (4.7)
10 (9.5)
Sarcomatoid
0 (0)
3 (2.9)
Poorly differentiated carcinoma
1 (1.6)
0 (0)
Adenosquamous
0 (0)
1 (1.0)
NSCLC with NET differentiation
0 (0)
1 (1.0)
Adenocarcinoma with SCLC component
1 (1.6)
0 (0)
Carcinoma of the lung
0 (0)
1 (1.0)
Clinical stage*, n (%)
0.942
I
6 (9.3)
8 (7.4)
II
4 (6.4)
5 (4.8)
III
10 (15.6)
16 (14.9)
IV
44 (68.7)
78 (72.9)
PD-L1 status, n (%)
0.704
<1%
13 (20.3)
20 (19.0)
1-49%
7 (10.9)
11 (10.5)
>50%
11 (17.2)
12 (11.4)
Missing
33 (51.6)
62 (59.0)
Initial Therapy, n (%)
0.772
Surgery +/- Chemotherapy
10 (18.2)
12 (12.9)
Radiation
5 (9.1)
9 (9.7)
Concurrent chemoradiation
7 (12.7)
14 (15.1)
Chemoimmunotherapy
6 (10.9)
12 (12.9)
Platinum-doublets
14 (25.5)
27 (29.0)
Pembrolizumab
4 (7.3)
6 (6.5)
Docetaxel
1 (1.8)
0 (0)
Vinorelbine
0 (0)
1 (1.1)
Gemcitabine
0 (0)
1 (1.1)
Pemetrexed
6 (10.9)
7 (7.5)
Targeted therapy
0 (0)
3 (3.2)
Clinical Trial
2 (3.6)
1 (1.1)
aFisher’s exact test p-value; NSCLC-NOS: non-small cell lung cancer, not otherwise specified; NET: neuroendocrine tumor; SCLC: small cell lung cancer; *stage at diagnosis; PD-L1: programmed death ligand-1
Although outcomes and demographics in KRAS G12C and non-G12C mutant NSCLCs appear to be largely comparable, our analyses suggest an association between the presence of G12C mutations and durable responses to immunotherapy. These findings will require validation in larger, prospective studies.
