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Alain Vergnenegre
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P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)
- 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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P1.04-35 - Quick Progression (QP) in Patients Treated by Nivolumab (IO) in 2nd Line or More for Non-Small Cell Lung Cancer: ERORECI Study (GFPC 2016-04) (ID 11936)
16:45 - 18:00 | Presenting Author(s): Alain Vergnenegre
- Abstract
Background
Nivolumab has been approved in 2nd line for advanced non-small cell lung cancer (NSCLC). However, more than half of the patients had progressive disease at 16 weeks, without any response and sometimes with deleterious progressions. This descriptive prospective study aimed to assess the characteristics of non responders with QP after IO and the following treatments.
a9ded1e5ce5d75814730bb4caaf49419 Method
From September 1st, 2016 to August 31th, 2017, patients (pts) treated by IO (second line or more) with QP<16 weeks were included by 20 GFPC centers. NSCLC characteristics at the diagnosis, at the IO initiation, treatments (before IO, IO and after IO) and outcomes responses, progression free survival (PFS) according to lines of treatments were recorded.
4c3880bb027f159e801041b1021e88e8 Result
The sample included 319 pts: 64,3y± 9,6, smokers/ex-smokers: 48.0%-42.9%, male: 70.8%, PS01/2: 92.8%-7.2%, stage IV at diagnosis: 71.8%; adenocarcinoma: 63.9%. K-Ras mutated: 25.7%. Only 29% of patients had a PDL1 determination. 93% of pts received first line therapy, 32% second line, 10.3% third line before IO. First line PFS (PFS1) was 6.9m [6.43-7.8], PFS2: 9.33m [1.2-19], PFS3: 4.1m [1.56-12.43]. PFS for IO was 1.7m [0.76-4.16]. 229 (71,8%) patients had a IO PFS<2m; 14.7% of these patients stopped the treatment for toxicity. Among the 146 pts evaluable for response, PR was found in 23% of cases, SD in 30%, and PD in 47%.The table describe a comparison between two groups of QP during IO.
8eea62084ca7e541d918e823422bd82e Conclusion
In real life, QP during IO remains a challenge in NSCLC. Multivariate analyses will be presented to characterize these patients.
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In collaboration with the GFPC* team and supported by an academic grant from Pierre-Fabre pharmaceuticals.
*GFPC: French Lung Cancer Group
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P2.03 - Biology (Not CME Accredited Session) (ID 952)
- 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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P2.03-15 - Integrin-Linked Kinase (ILK), Protein Tyrosine Phosphatase SHP2 and B lymphoma Mo-MLV Insertion Region 1 Homolog (Bmi-1) in EGFR-Mutant NSCLC (ID 12557)
16:45 - 18:00 | Author(s): Alain Vergnenegre
- Abstract
Background
The clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC) is jeopardized by the activation of multiple signaling pathways. ILK regulates the expression of Bmi-1, a well-known epithelial mesenchymal transition-inducing transcription factor. SHP2 function is required for MAPK pathway activation, and also plays a role in receptor tyrosine kinase signaling pathways.
a9ded1e5ce5d75814730bb4caaf49419 Method
Clinical data were assessed in accordance with the protocol approved by the institutional review board and de-identified for patient confidentiality. Pretreatment tumor specimens from advanced EGFR-mutant NSCLC patients (pts) were collected from eight sites in Spain, France, Italy and Colombia. mRNA gene expression analysis was performed by TaqMan (qRT-PCR). We examined the mRNA levels of ILK, SHP2 and Bmi-1.
4c3880bb027f159e801041b1021e88e8 Result
With a median follow-up of 26.7 months, median progression-free survival (PFS) was 9.3 (95% CI, 7.6-14.2) and 15.7 months (95%CI, 12.3-30.1) for pts with high and low ILK mRNA, respectively (P=0.0002), (HR for disease progression, 2.4; 95% CI, 1.3-4.5; P=0.002). Median PFS was 11.4 (95% CI, 8.2-14) and 24.1 months (95% CI, 8.2-30.9) for pts with high and low SHP2 mRNA, respectively (P=0.009), (HR, 2.4; 95% CI, 1.2-4.7; P=0.01). Median PFS was 8.2 (95% CI, 4.8-13.1) and 24.1 months (95% CI, 14.2-36.5) for pts with high and low SHP2 mRNA, respectively (P=0.001), (HR, 2.9; 95% CI, 1.4-5.9; P=0.002). Median overall survival (OS) was 17.9 (95% CI, 13.2-33) and 34.4 months (95% CI, 18.5-44.2) for pts with high and low ILK mRNA, respectively (P=0.200), (HR, 1.5; 95% CI, 0.79-3; P=0.200). Median OS was 18.5 (95% CI, 14-33) and 36.7 months (95% CI, 16.7-47.1) for pts with high and low SHP2 mRNA, respectively (P=0.018), (HR, 2.5; 95% CI, 1.1-5.8; P=0.020). Median OS was 17.6 (95% CI, 8.6-39.1) and 36.7 months (95% CI, 19.1-64.1) for pts with high and low Bmi-1 mRNA, respectively (P=0.004), (HR, 2.2; 95% CI, 1.0-5.1; P=0.040).
8eea62084ca7e541d918e823422bd82e Conclusion
The disturbance of RTKs, including ILK-SHP2-Bmi-1 axis, occurs frequently in EGFR mutant NSCLC patients, significantly limiting the PFS and OS. The levels of ILK, SHP2 and Bmi-1 could be predictive for upfront combinatory therapy of EGFR TKI plus a MAPK pathway inhibitor (SHP2 or MEK inhibitors).
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P2.15 - Treatment in the Real World - Support, Survivorship, Systems Research (Not CME Accredited Session) (ID 964)
- 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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P2.15-29 - Eligibility for Anti-Angiogenic Treatments in Patients with Squamous Non-Small Cell Lung Cancer (SQ-NSCLC): EPISQUAMAB Study (GFPC 2015-01) (ID 11338)
16:45 - 18:00 | Presenting Author(s): Alain Vergnenegre
- Abstract
Background
Antiangiogenic treatments are today restricted to non-squamous NSCLC. New drugs, like ramucirumab, have been approved in second line setting for advanced NSCLC regardless histology but there is little information about the rate of squamous NSLC eligible to these treatments. This descriptive, prospective, observational study aimed to assess the rate of squamous advanced NSCLC patients eligible to anti-angiogenic treatments.
a9ded1e5ce5d75814730bb4caaf49419 Method
Each participating center had to include consecutive relapsed advanced SQ-NSCLC and to assess the presence of common criteria which restricted the use of antiangiogenic treatments (hemoptysis, cardiovascular diseases, tumoral extension to blood vessels and tumoral cavitation).
4c3880bb027f159e801041b1021e88e8 Result
From july 2016 to july 2017, 317 patients were included: 256 (80.8%) men, PS0/1/2 in 30.5%/54.5%/14.9% patients, stage IV in 74.5% of cases. Ineligibility criteria for anti-angiogenic therapy were found in 53.6% of patients (one single criteria in 29,3%, two criteria in 19,9%, three in 3.5%). The main reasons for ineligibility was as followed: blood vessel extension 39.8%, cavitation 20.5%, hemoptysis 7.2%, cardiovascular diseases 12.1%.
Table described patients characteristics according to the ineligibility criteria: Cavitation had the highest number of metastatic disease, cardiovascular diseases the highest number of men and number of metastatic site.
8eea62084ca7e541d918e823422bd82e Conclusion
In a non-selected advanced SQ-NSCLC population, only half of these patients are ineligible to a second line anti-angiogenic treatments with a wide majority of tumoral blood vessel extensions and cavitations.
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In collaboration with the GFPC* team and supported by an academic grant from Lilly pharmaceuticals.
*GFPC: French Lung Cancer Group
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