Virtual Library
Start Your Search
Ernest Nadal
Author of
-
+
OA01 - Improving Outcomes in Locoregional NSCLC I (ID 892)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 10:30 - 12:00, Room 107
-
+
OA01.05 - Phase II Study of Neo-Adjuvant Chemo/Immunotherapy for Resectable Stages IIIA Non-Small Cell Lung Cancer- Nadim Study-SLCG (ID 12907)
11:15 - 11:25 | Author(s): Ernest Nadal
- Abstract
- Presentation
Background
The combination of chemotherapy and immunotherapy (CT-IO) has a high response rate and longer survival in unselected patients (pts) with metastatic non-small cell lung cancer (NSCLC). There are no data about this combination in the neoadjuvant setting.
a9ded1e5ce5d75814730bb4caaf49419 Method
A Phase II, single-arm, open-label multicenter study of local-advanced resectable stage IIIA N2-NSCLC adult patients with CT plus IO (nivolumab (NV)) followed by adjuvant treatment for 1 year. Neoadjuvant treatment: Three cycles of NV 360mg IV Q3W + paclitaxel 200mg/m2 + carboplatin AUC 6 IV Q3W. After completing neoadjuvant therapy, tumor assessment is performed in patients prior to surgery. Surgery is performed in the 3rd or 4th week after day 21 of the third cycle of neoadjuvant treatment. Adjuvant treatment: NV 240mg IV Q2W for 4 months and NV 480mg IV Q4W for 8 months (total one year) after surgical resection. The study aims to recruit 46 pts. The primary endpoint is Progression-Free Survival (PFS) at 24 months. Efficacy is explored using objective pathologic response criteria. We present preliminary data on patients that completed 3 cycles and underwent surgical resection.
4c3880bb027f159e801041b1021e88e8 Result
At the time of submission, 46 pts had been included and 20 underwent surgery. CT-IO was well-tolerated and surgery was not delayed in any patient. None of the pts was withdrawn from the study preoperatively due to progression or toxicity.
Twenty surgeries had been performed and all tumors were deemed resectable. The overall clinical response rate was 5% complete (CR) and 65% PR. The pathological response evaluated after surgery: 13 cases (65.0%) achieved CR (CPR) (95% CI 40.8-84.6%), and 3 (15.0%) had a major pathologic response (MPR), defined as <10% viable tumor cells in the resection specimen. Considering both CPR and MPR, the overall response rate was 80.0% (95% CI 56.3-94.3%) and 60% of complete responses were unsuspected
8eea62084ca7e541d918e823422bd82e Conclusion
This is the first multicentric study testing CT-IO in the neoadjuvant setting with promising antitumor activity in locally advanced, potentially resectable NSCLC yields an unprecedented complete pathologic response rate. The data will be updated at the time of the congress. EudraCT Number: 2016-003732-20
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
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
-
+
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): Ernest Nadal
- 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
-
+
P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
-
+
P1.13-29 - Overall Response Rate of Nintedanib and Docetaxel in Combination with the Nutraceutical Use of Silibinin in Advanced NSCLC (ID 13239)
16:45 - 18:00 | Author(s): Ernest Nadal
- Abstract
Background
The bioactive flavonolignan silibinin, the main component of standardized extracts from the seeds of the milk thistle herb Silybum marianum, has been shown to exhibit significant anticancer activity in preclinical models. Silibinin is a direct inhibitor of pSTAT3, a signal transducer and key transcription factor that is associated with chemoresistance in cancer cells. Our group has shown that oral administration of the silibinin-containing nutraceutical Legasil® could represent the first silibinin formulation with proven clinical benefit as an adjunct cancer treatment in patients with brain metastases. Nintedanib is an orally administered, small-molecule triple angiokinase inhibitor of VEGF1–3, PDGFa and b, and FGFR1–3. The LUME-Lung 1 trial showed that nintedanib significantly extended progression-free survival (PFS) and overall survival (OS) in patients with NSCLC adenocarcinoma when added to docetaxel chemotherapy, with no differences in response rate.
a9ded1e5ce5d75814730bb4caaf49419 Method
Patients with stage IV NSCLC who failed ≥1 prior treatment were eligible for nintedanib/docetaxel combination. We present retrospective data analysis regarding patients that received nintedanib/docetaxel with or without combination with up to 5 capsules (630 mg)/day of Legasil®.
4c3880bb027f159e801041b1021e88e8 Result
Fifty-nine patients were enrolled in the study: median age, 60y (range: 43–79); male, 46 (78%). All the cases had adenocarcinoma histology. All patients had received first line therapy and 13 (22%) patients had >2 prior lines of treatment. A higher overall response rate (ORR) was observed in the group receiving Legasil® supplementation: ORR 55.5% versus 22%, p=0.02. No statistically significant differences in the median PFS were observed in the two arms: 2.34 months (95% confidence interval [CI] 1.83–2.91) for nintedanib/docetaxel combination (n=41) versus 4.99 (95%CI 0.94–9.05) for nintedanib, docetaxel and Legasil® triple combination (n=18) (p=0.241) at the data cut-off of January 2018. In the control group (n=41), ORR was greater in patients with known KRAS (n=8) or EGFR (n=3) mutations: 45% versus 13%, p=0.028.
8eea62084ca7e541d918e823422bd82e Conclusion
The inhibition of pSTAT3 with silibinin may increase tumor responses to nintedanib/docetaxel combination. In addition, patients with known KRAS or EGFR mutations may show higher tumor responses to nintedanib/docetaxel combination.
6f8b794f3246b0c1e1780bb4d4d5dc53
