Virtual Library
Start Your Search
Sara Pilotto
Author of
-
+
MA07 - Clinical Questions and Potential Blood Markers for Immunotherapy (ID 125)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:David R Spigel, Roberto Ferrara
- Coordinates: 9/08/2019, 13:30 - 15:00, Vancouver (2003)
-
+
MA07.04 - Discussant - MA07.01, MA07.02, MA07.03 (Now Available) (ID 3739)
13:30 - 15:00 | Presenting Author(s): Sara Pilotto
- Abstract
- Presentation
Abstract not provided
Only 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.
-
+
P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
-
+
P1.14-26 - ALK Fusion Variant Detection by Targeted RNA-Seq in TKIs Treated ALK-Positive Lung Adenocarcinoma (ID 1860)
09:45 - 18:00 | Author(s): Sara Pilotto
- Abstract
Background
Clinical outcomes of ALK positive (ALK+) Non-Small-Cell Lung Cancer (NSCLC) and the identification of the most effective anaplastic lymphoma kinase inhibitor (ALKi) according to the specific ALK fusion variants are not well assessed. We retrospectively characterized fusion variant distribution in a cohort of ALK+ lung adenocarcinomas (ADC) with paired clinical data about treatments and outcomes.
Method
Diagnostic tumor tissue from advanced ALK+ (by FISH and/or IHC) ADC diagnosed from 2010 to 2018 and treated with single or multiple ALKis were collected (expanded cohort from Gobbini et al. Lung Cancer, 2017). The OncomineTM Solid Tumor Fusion Transcript Kit on an Ion PGM™ system and the Ion Reporter™ software were used to identify targeted ALK fusion gene products (ThermoFisher).
Result
Specific fusion variant transcripts were found in 34/55 (62%) of collected samples. As expected, EML4-ALK fusion transcripts were the most common (31/34 samples, 91%), but HIP-ALK transcripts were also detected (3/34 - 9%). Among EML4-ALK fusions the following variants were detected: V1 (n=11); V2 (n=2); V3a/b (n=12 ) V5a/b (n=5 ) and E6A19 (n=1). Patient median age was 60 year [range 36-85], 22 were male and 12 female. Three patients were current, 11 former and 20 never smokers. Crizotinib, alectinib, ceritinib, brigatinib and lorlatinib were the ALKis used. Independently of the therapy line, 12 patients received crizotinib only, while 22 patients received crizotinib followed by one or two other ALKis. Regardless of the type of transcript, those patients who received more than one ALKi had a better median overall survival compared to those receiving crizotinib only, as expected (74 vs 21 months, HR: 5.31; 95%CI: 1.464-19.26, log rank p=0.0006). Furthermore, a significant difference in the mean duration of the different ALKi treatment was found according to the ALK variants (Chi-square p<0.0001), suggesting a private ALKi efficacy profile for specific fusion variants. Finally, the 3 HIP-ALK cases showed a better outcome with respect the EML4-ALK variants (not reached vs 51 months).
Conclusion
Our analysis suggests that different ALK fusion variant might affect ALKi treatment duration in ALK+ lung ADC.
-
+
P1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 186)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
-
+
P1.16-43 - Prevalence of Clinical and Sub-Clinical Malnutrition in Advanced Non-Small-Cell Lung Cancer Patients and Association with Outcome (ID 1757)
09:45 - 18:00 | Presenting Author(s): Sara Pilotto
- Abstract
Background
While weight loss and lean body mass wasting are common hallmarks of non-small-cell lung cancer (NSCLC), their early detection and management are usually overlooked in clinical routine. The present study aimed to explore the prevalence of malnutrition and its correlation with outcome in advance (A)-NSCLC pts.
Method
A-NSCLC pts treated at AOUI of Verona (2016-2018) received nutritional counseling by a qualified dietitian. Prevalence of malnutrition was assessed by nutritional screening score (NRS). Bilateral psoas major muscles were measured at L3 vertebrae level with routine staging-computed tomography (CT). Changes in psoas muscles observed in subsequent scans were evaluated using Wilcoxon signed-rank test. Clinical, pathological and nutritional data were correlated to progression-free/overall survival (PFS/OS) and response rate (ORR) using a Cox and logistic regression model. Kaplan-Meier curves were compared with Log-Rank.
Result
Data from 38 pts (20 males [52.6%], 18 females [47.4%]) were gathered (median age 59 years [range 42-82], with a median follow-up of 21 months (range 1-197). At baseline, 18.4% were underweight, 18.4% normal weight, 34.2% overweight and 31.6% obese. The majority (65.8%) were at risk of malnutrition (NRS≥3). At multivariate analysis, stage (HR 4.99, 95% CI 1.05-27.74, p = 0.04), performance status (HR 4.99, 95% CI 1.55-16.03, p = 0.007) and NRS (HR 7.61, 95% CI 1.52-38.11, p = 0.01), were significant independent predictors for PFS. Pts with baseline NRS≤3 had significantly longer 1-year PFS (58.6% vs 16.7%, p = 0.04) and 2-year OS (90.6% vs 68.3%, p = 0.03) and a better ORR than those with NRS > 3 (66.7% vs 21.4%). Conversely, BMI did not affect PFS/OS. A significant loss in psoas muscle mass was detected in pts treated with both immunotherapy and other therapies (p = 0.01 and p=0.002, respectively). Of interest, in immunotherapy-treated pts (n = 16) loss in psoas muscle mass correlated with worse ORR, PFS and OS, although differences did not reach a statistical significance due to the limited sample.
Conclusion
Our analysis suggests that malnutrition has a detrimental impact on ORR, PFS and OS in A-NSCLC. Particularly, in pts treated with immunotherapy, muscle mass wasting seems to impact on efficacy outcome, suggesting a potential interaction between immunological and nutritional parameters. Therefore, the introduction in the clinical routine of a comprehensive nutritional profiling and monitoring, beyond body weight and BMI, is highly recommended in A-NSCLC. A comparison between NSCLC pts who underwent a personalized nutritional intervention during therapy and who did not is ongoing, together with a series of biomolecular analysis.
-
+
P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
-
+
P2.01-15 - Phase II Single Arm Study of CABozantinib in Non-Small Cell Lung Cancer Patients with MET Deregulation (CABinMET) (ID 2637)
10:15 - 18:15 | Author(s): Sara Pilotto
- Abstract
Background
Mesenchymal-Epithelial Transition gene (MET) amplification and exon 14 skipping mutations are established oncogenic drivers in non-small cell lung cancer (NSCLC), both occurring in about 4% of cases. In patients with MET amplified or mutated lung cancer, oral MET tyrosine kinase inhibitors (TKI) showed promising activity. The American Food and Drug Administration has recently granted crizotinib a breakthrough therapy designation for MET exon 14 mutation positive NSCLC. Cabozantinib is a novel oral inhibitor of MET and other receptor tyrosine kinases that has shown preliminary activity in MET deregulated NSCLC patients pretreated with crizotinib, although definitive data on its therapeutic role are still missing.
Method
CABinMET (NCT03911193) is a phase II, single arm, multicenter study assessing the efficacy of cabozantinib in subject with MET amplification or MET exon 14 skipping mutation pretreated or not with MET inhibitors. The primary endpoint of the trial is overall response rate. Secondary efficacy endpoints are progression free survival, overall survival and disease control rate. Main inclusion criteria include histologically/cytologically confirmed diagnosis of advanced stage NSCLC, presence of MET exon 14 skipping mutation or MET amplification (MET/CEP7 ratio ≥2.2 on FISH analysis) on archival formalin-fixed paraffin-embedded (FFPE) tumor tissue or circulating tumor DNA, measurable disease, ECOG PS 0-1, at least 1 prior line of standard therapy, adequate organ function. Patients with co-existent driver events or with symptomatic brain metastases are excluded from the trial. Cabozantinib is administered orally at 60 mg once daily until disease progression, patient refusal or unacceptable toxicity. Disease is assessed every 8 weeks. Exploratory biomarker analyses are conducted on archival FFPE tumor tissue and on blood samples collected at baseline, at the time of the first disease assessment and at progression.
Result
The study is currently running in 9 Italian centers. Recruitment started in September 2018 and 6 of the planned 25 patients have been enrolled.
Conclusion
Enrollment will be completed in 24 months.
-
+
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
-
+
P2.04-51 - A 6-Gene Immune Genomic Signature (IGS) Predicts Resistance to Nivolumab [NIV] in Advanced Pretreated NSCLC: Results of PRINCiPe Trial (ID 1885)
10:15 - 18:15 | Presenting Author(s): Sara Pilotto
- Abstract
Background
Genomic abnormalities detected in immune-escape/editing-related genes may promote immunotherapy resistance. In the light of this hypothesis, we designed the PRINCiPe (Predictors of Resistance to Immunotherapy with NIV) study in APNSCLC.
Method
FFPE-tumor blocks of APNSCLC pts undergone NIV were retrospectively sequenced for Somatic Mutations/Copy Number Variations (SM/CNV) (Ampliseq 17-genes customized panel: APLNR, B2M, IFNAR1, IFNAR2, IFNGR1, IFNGR2, IRF9, JAK1, JAK2, JAK3, PIAS4, PTPN2, SOCS1, STAT1, STAT2, STAT3, TYK2). End-points of the PRINCiPe study were overall-, progression-free-survival (OS/PFS) and objective response rate (ORR).
Result
Forty-four APNSCLC pts were gathered (median age 69.5 yrs, median number of previous lines 3 [2-5], 2nd line NIV [75.0%], male/female 77.3/22.7%, squamous/non-squamous 31.8/68.2%, EGFR mutant 5 [11.4%], median follow-up 6.8 months [range 1-23], deaths 24 [54.5%]). JAK3/JAK2 (7/3 pts, 15.9/6.8%) CNV and IFNAR2 SM (4 pts, 9.1%) were the most frequent (>1 pts) abnormalities. Pts (n=15) with JAK3, PIAS4, PTPN2, STAT3, IFNAR2 SM and/or JAK2/3 CNV (IGS+) had a significantly lower PFS than those without (IGS-) (median PFS 2.8 vs. 6.6 months; p=0.006), while a trend towards significance was observed in terms of OS (median OS 5.1 vs. 13.0 months for IGS+ and IGS-, respectively; p=0.06 log-rank, p=0.05 Tarone-Ware). At multivariate analysis, IGS+ was independently associated with a shorter PFS (HR 2.64, 95% CI 1.3-5.4, p=0.008). IGS+ pts were significantly more probable to be affected by liver metastases than those without (p=0.01).
Conclusion
The identified IGS appears to select APNSCLC pts with a significant lower chance to benefit from NIV, supporting intrinsic resistance. A prospective larger and external validation is ongoing, as well as the comprehensive transcriptome analysis.
