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Ivana Sullivan
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-68 - Correlation of the Lung Immune Prognostic Index (LIPI) and PDL1 Status with Outcomes for Immune Checkpoint Inhibitors in Advanced NSCLC Patients (ID 14256)
16:45 - 18:00 | Author(s): Ivana Sullivan
- Abstract
Background
Baseline LIPI, based on derived NLR (neutrophils/[leucocytes-neutrophils]) and lactate dehydrogenase (LDH) was associated with outcomes for immune checkpoint inhibitors in advanced NSCLC patients. We assessed the correlation between LIPI and PDL1 for ICI outcomes in NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Method
Baseline dNLR and LDH and clinical data were retrospectively collected in advanced NSCLC patients, treated with PD1/PDL1 +/- CTLA4 inhibitors from Nov. 2012 to Mar. 2018, in a multicentric cohort (N=794) from 11 centers. LIPI stratified 3 groups: good (dNLR<3+LDH<upper limit of normal (ULN), intermediate (dNLR>3 or LDH>ULN), poor risk (dNLR>3+LDH>ULN). PDL1 positivity was defined as ≥ 1% tumor cells expression by immunohistochemistry.
4c3880bb027f159e801041b1021e88e8 Result
476 patients (60%) were male, 693 (87%) smokers, 695 (88%) had PS ≤1, with median age 65; 576 (73%) had nonsquamous histology. PDL1 was ≥ 1% in 195 (70%) patients, negative in 82 (30%), and unknown in 517. The median of prior lines was 1 (0-11). The median PFS and OS were 4 months (m) [95% CI 4-5] and 12 m [10-15]. dNLR was>3 in 276 (35%) and LDH>ULN in 290 (37%) patients. LIPI stratified 349 patients as good (44%), 323 (41%) as intermediate and 121 (15%) as poor LIPI risk groups. LIPI was an independent factor for OS (table) and PFS (HR 2.58; CI 1.3-5.2, P=0.02). ≥ 1% PDL1 and ≥ 50% PDL1 were not correlated with OS and PFS. Median OS for good, intermediate, and poor LIPI risk groups were 21 m [17-23], 11 m [9-14] and 4 m [2-6], respectively (P=<0.0001). Median PFS for good, intermediate, and poor risk was 5 m [5-7], 4 m [3-5], and 2 m [1-3], respectively (P=0.0005). No differences were observed in LIPI groups according to the PDL1 expression.
8eea62084ca7e541d918e823422bd82e ConclusionMultivariate analysis for OS
HR
95% CI
P value
Immunotherapy line
>2
2.117
0.641
6.992
0.219
N# Metastasis sites
≥2
1.242
0.727
2.121
0.428
Performance status
≥2
2.141
1.059
4.332
0.034
Albumin
>35 g/dL
0.867
0.507
1.48
0.6
LIPI
Intermediate
Poor
1.697
4.178
0.917
1.956
3.142
8.925
0.001
PDL1 IHC
≥1%
0.713
0.406
1.252
0.239
Baseline LIPI is associated with ICI outcomes in advanced NSCLC, regardless the PDL1 expression. LIPI should be evaluated in prospective clinical trials.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.17 - Treatment of Locoregional Disease - NSCLC (Not CME Accredited Session) (ID 966)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.17-17 - Multimodal Treatment in Pathologically Confirmed Single-Station Resectable IIIA-N2 Non-Small Cell Lung Cancer: A Single Center Experience (ID 13747)
16:45 - 18:00 | Author(s): Ivana Sullivan
- Abstract
Background
The management of patients with resectable stage IIIA-N2 (7th Edition) non-small cell lung cancer (NSCLC) is controversial. Multimodal treatment with neoadjuvant chemotherapy (CT) and radiotherapy (RT) followed by surgery may be recommended for a selected group of patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
We have retrospectively analyzed 21 patients with single-station resectable stage IIIA-N2 NSCLC treated in our center from April 2011 to June 2017. N2 was confirmed by EBUS or mediastinoscopy. Patients received CT with cisplatin (70 mg/m2)/carboplatin (5AUC) + vinorelbine (25 mg/m2 C1, 15 mg/m2 C2-3) concurrent RT with the 2nd cycle of CT with a total dose of 60Gy. PET-CT and mediastinoscopy was performed after induction treatment, and only those patients with mediastinal downstaging disease were proposed for surgery (lobectomy + systematic lymph node dissection). Kaplan-meier analysis was used to evaluate local control (LC), Overall survival (OS), Cause-specific-survival (CSS) and Disease-free-survival (DFS).
4c3880bb027f159e801041b1021e88e8 Result
13 patients were males (62%) and 8 females (38%), median age was 63 (52-75). Histology was: 10(48%) adenocarcinoma, 6(28%) squamous and 5 (24%) NOS NSCLC. Surgery was not performed in 5 patients (24%): 1 presented progressive disease, 2 had persistent mediastinum disease and 2 were excluded due to comorbidities. No severe postoperative complications were observed in patients who underwent surgery. Table 1 shows the results.
With a median follow up of 49 (10-84) months, significant differences in terms of OS (p=0,002) and in CSS (p=0,006) were observed between patients with/without surgery, with no difference in LC and DFS. In patients who underwent surgery, there was a trend to a better LC, OS, CSS, DFS when complete pathological response was achieved.
8eea62084ca7e541d918e823422bd82e Conclusion
In patients with pathologically confirmed single-station resectable stage IIIA-N2 NSCLC multimodal treatment with high dose
radiotherapy is feasible and with a trend to better outcome in patients with complete pathological response.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P3.04 - Immunooncology (Not CME Accredited Session) (ID 970)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.04-16 - A Seven-Gene Expression Signature Reveals Unique Immune-Phenotypes Related to Major Oncogenic-Drivers in NSCLC (ID 13991)
12:00 - 13:30 | Author(s): Ivana Sullivan
- Abstract
Background
In oncogenic-driven non-small cell lung cancer (NSCLC), programmed death ligand 1 (PD-L1) expression is the result of a constitutive oncogenic activation leading to an immunosuppressive microenvironment. However, the relationship between the major driver mutations (KRAS, EGFR and ALK) and PD-L1 and other immune markers remains unclear. Gene expression signatures incorporating not only PD-L1 but also other components of the stroma might better capture the immune-context of these oncogenic subgroups.
a9ded1e5ce5d75814730bb4caaf49419 Method
A 7-gene ‘immune signature’ comprising CD4, CD8, PD-1, PD-L1, IFNG, GZMM and FOXP3 was included in a customized nCounter panel (NanoString Technologies), used in our clinical institution on a routine basis and designed to simultaneously screen for gene fusion drivers (ALK, ROS1, RET and NTRK1), MET overexpression and MET exon 14-skipping mutations in formalin-fixed paraffin embedded (FFPE) samples. A total of 296 advanced NSCLC patients from two different institutions were analyzed by the panel. Among them, 115 patients (38.9%) were also submitted to next-generation sequencing (NGS, Ion Torrent PGM® or GeneReader) . Analyses of variance (ANOVA) were used to describe statistical significance between immune response genes in the two major oncogenic groups: KRAS mutant (n=33) andALK rearranged (n=44), compared to wild-type (WT) tumor samples (n=38).
4c3880bb027f159e801041b1021e88e8 Result
Oncogenic genes (ALK, KRAS) were mutually exclusive. The analysis of the 7-gene signature revealed distinct expression patterns in the oncogenic biomarker groups. A significantly higher mRNA expression of CD4 and PD-L1 was found in ALK rearranged tumors compared to the KRAS mutant, and WT groups (p=0.0014 and p=0.0467, respectively). In addition, a trend was observed between GZMM mRNA levels and the oncogenic groups (p= 0.0665) whereas no association was found with the other immune genes (CD8, PD-1, IFNG, FOXP3). There was a significant linear correlation between CD4 and PD-L1 in ALK positive patients (p= 0.0214), but not in KRAS mutant samples (p= 0. 112). Unsupervised clustering across mRNA expression data from 296 samples using 7-immune-related genes showed two clusters, high expression for ALK-rearranged patients and low expression for KRAS mutant patients. The correlation between each of the immune genes was performed and a high correlation was found between PD-1 and FOXP3 (r=0.9) and PD-1 with GZMM (r=0.8).
8eea62084ca7e541d918e823422bd82e Conclusion
NSCLC tumors with ALK alterations show a distinct CD4 and PD-L1 immune profile when compared to KRAS and WT samples.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P3.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 978)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.12-11 - Association of the Lung Immune Prognostic Index (LIPI) with Outcomes for Immune Checkpoint Inhibitors in Diffuse SCLC Patients (ID 14200)
12:00 - 13:30 | Author(s): Ivana Sullivan
- Abstract
Background
Pretreatment LIPI (Lung Immune Prognostic Index), based on derived NLR (neutrophils/[leucocytes-neutrophils] ratio) and lactate dehydrogenase (LDH) has been associated with outcomes for immune checkpoint inhibitors (ICI) in advanced NSCLC patients. We tested whether LIPI has the same role in diffuse small cell lung cancer (SCLC) patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
Baseline dNLR and LDH and clinical data were retrospectively collected in SCLC patients, treated with ICI (PD1 inhibitor, PDL1 inhibitors +/- CTLA4 inhibitor) from April 2014 to Jan. 2018 (N=66) from 6 European centers. LIPI was calculated combining dNLR and LDH, stratifying 3 risk groups: good (dNLR<3+LDH<upper limit of normal (ULN), intermediate (dNLR>3 or LDH>ULN), poor (dNLR>3+LDH>ULN). The primary endpoint was overall survival (OS), and secondary endpoint was progression-free survival (PFS).
4c3880bb027f159e801041b1021e88e8 Result
Fifty-three patients (80%) were males, 58 (88%) smokers and all patients had PS ≤1, with median age 63 years (41-82). PDL1 was ≥ 1% by immunohistochemistry in 6 patients, and unknown in 60 patients. The median of prior lines was 1 (0-6). Platinum-based therapy was the prior line in 63 (95%) patients, with ORR of 88%. The median PFS and OS with ICI were 2.7 months (m) [95% CI 1.87-4.43] and 10.3 m [95% CI 5.8-12.6]. dNLR was greater than 3 in 16 (25%) and LDH> Upper Limit of Normal (ULN) in 33 (50%) patients. Based on both, LIPI stratified the population in 3 groups: 26 patients as good (40%), 29 (45%) as intermediate and 10 (15%) as poor LIPI risk groups. LIPI was an independent factor for OS (HR 2.77, 95% CI 1.07-7.14, P=0.03) and PFS (HR 3.13, 1.37-7.16, P=0.01). Median OS for good, intermediate, and poor risk groups were 11.4 m [95% CI 5.5-27.3], 11 m [95% CI 6.8-not-reached (NR)] and 2.3 m [95% CI 0.7-NR], respectively (P=0.004). Median PFS for good, intermediate, and poor risk groups were 3 m [95% CI 1.9-12.6], 2.8 m [95% CI 1.6-6.0 and 1.2 m [95% CI 0.47-NR], respectively (P=0.004).
8eea62084ca7e541d918e823422bd82e Conclusion
Baseline LIPI poor risk group is associated with poor outcomes for ICI in diffuse SCLC patients. LIPI effect in a validation cohort is currently evaluated.
6f8b794f3246b0c1e1780bb4d4d5dc53
