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EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
EP1.01-41 - Feasibility of EBUS-TBNA Cytologies for an Extensive Assessment of Predictive Biomarkers in Lung Cancer (Now Available) (ID 1640)
08:00 - 18:00 | Author(s): Roxana Reyes
Clinical guidelines support the determination of several driver genes as well as PD-L1 to drive treatment decisions in non-small cell lung cancer (NSCLC). Endobronchial-ultrasound transbronchial needle aspiration (EBUS-TBNA) cytology specimens are useful for the initial diagnosis of NSCLC, although its capacity to provide enough material for a complete genotyping remains controversial. The aim of this study is to determine the yield of EBUS for a comprehensive multiplex genotyping in patients (pts) with suspected NSCLC.Method
In this single-center, ongoing, prospective study, samples from mediastinal lymph nodes were obtained from pts undergoing EBUS-TBNA for lung cancer diagnosis/staging. Following malignant confirmation and appropriate cell content by rapid on-site evaluation, the study sample was obtained and formalin-fixed paraffin-embedded (FFPE). Three analytes were evaluated (DNA/RNA/protein). DNA and RNA were extracted and analyzed by Oncomine Solid Tumour panel (22 genes) and a customized nCounter panel (ALK, ROS; RET, NTRK, METDe14). Tumor Proportion Score (TPS) for PD-L1 protein expression was evaluated by an expert pathologist and scored into <1% (negative), 1-49% (weakly positive) and 50% (high).Result
Twenty-five pts with NSCLC have been included and cytology samples of 20 of them molecularly characterized (5 still in progress). Overall, cytological analysis of EBUS-TBNA yield a complete characterization for the three analytes (DNA/RNA/protein) in 15 pts (75%). EBUS-TBNA sampling was sufficient for both, Nanostring and Oncomine evaluation, in a total of 18 pts (90%): 15 patients (83%) had any alteration detected by oncomine (TP53 61% [11/18],KRAS 44% [8/18], EGFRe 195.5% [1/18], BRAF V600E 5,5% [1/18], DDR2 5.5% [1/18], STK11 11% [2/18]) and 1 pt (5.5 %) by nanostring (METDex14). A total of 19 samples were sufficient for PD-L1 expression scoring (95%). TPS for PD-L1 expression was negative in 8 pts (42%), week in 4 (21%) and high in 7 pts (37%). Overall, half of the pts evaluated (10/20) would be potential candidates for an upfront personalized treatment strategy using targeted agents or immunotherapy.Conclusion
EBUS-TBNA is a promising alternative source of material for NSCLC genotyping and allows the identification of pts candidates for personalized therapies.
P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 2
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
P2.04-22 - Programmed Death 1-mRNA Expression Predicts Benefit to Anti-PD1 Monotherapy in a Prospective Cohort of Advanced NSCLC (ID 1092)
10:15 - 18:15 | Author(s): Roxana Reyes
Immunotherapy (IO) targeting PD1 or PD-L1 represents a new treatment option for patients (pts) with advanced non-small cell lung cancer (NSCLC). Besides PD-L1 IHC, other predictive biomarkers are being explored as potential predictors of outcomes. Our group has recently described an association between PD1-mRNA expression and response to IO in a retrospective multi-tumor dataset (Annals Oncol 2018). We aimed to corroborate these results in a prospective cohort of advanced NSCLC.Method
We prospectively evaluated the expression of 7 immune-related genes (CD4, CD8, PD1, PDL1, IFNG, GZMM andFOXP3) and 5 housekeeping genes in formalin-fixed paraffin-embedded tumor samples obtained before anti-PD1 therapy using the nCounter platform (Nanostring Technologies). The study cohort included consecutive pts with advanced NSCLC, ECOG/PS 0-1, no targetable oncogenes, treated in the first or second-line setting with anti-PD1 monotherapy from June 2017 to January 2019. Associations between the expression of PD1 mRNA (as a continuous variable and using a previously defined pre-specified cutpoint) and response (complete and partial response) were assessed using logistic regression analysis. Kaplan-Meier method was used for survival analysis. PD-L1 IHC tumor cell expression was assessed using the 22C3 clone. Pearson correlation between PD-L1 IHC and PD1 mRNA was explored.Result
A total of 43 pts were included (men 79%; adenocarcinoma 53%; nivolumab 55%; pembrolizumab 45%; first-line 30%; second-line 70%). Response occurred in 23% of pts and was significantly associated with PD1 (p=0.029) and FOXP3 (p=0.035) expression. Using the pre-established PD1 cutoff (Annals Oncol 2018), 37% and 63% samples were PD1-high and PD1-low, respectively. PD1-high was significantly associated with increased overall response rate (ORR) (43% vs 11%, OR=6.22 [CI=1.31-29.44], p=0.021) and progression-free survival (HR 0.36 [CI= 0.14-0.90], p=0.028) but not with overall survival (p=0.117). PD-L1 IHC expression was available in 35 cases, of which 46% had high (>=50%) expression levels. A moderate concordance (0.49) was observed between PD-L1 IHC and PD1-mRNA. In this subset analysis, high PD-L1 IHC was significantly associated with response (50% vs 11%, OR=8.50 [CI= 1.45-49.53], p=0.043). Importantly, when combining predefined high/low-sets for both biomarkers (PD-L1 IHC/PD1-mRNA), response was significantly increased in PD-L1-high/PD1-high compared to PD-L1-low/PD1-low (ORR 58% vs 0%, p=0.019).Conclusion
PD1-mRNA expression is associated with response to anti-PD1 monotherapy and can increase the predictive ability of PD-L1 IHC. Further validation of these findings in pivotal clinical trials evaluating IO in advanced NSCLC pts seems warranted.
P2.04-61 - Preliminary Report of a Multidisciplinary Task Group for the Study of Immune-Mediated Pulmonary Toxicity (ID 1647)
10:15 - 18:15 | Author(s): Roxana Reyes
Immunotherapy (IO) is now the standard of care for many tumor types. However, it is not free of risks, being pulmonary toxicity one of the most relevant immune-related adverse event due to its severity. Differential diagnosis with other pulmonary complications such as infections or tumor dissemination further complicates its management.Method
In order to raise awareness, gather information, and to discuss early management strategies in patients (pts) with immune-related interstitial lung disease (irILD), in 2017 we created a multidisciplinary task group comprised of pneumologists, pathologists, oncologists and radiologists. We herein report the main features of the first series of pts treated with IO who subsequently developed ILD, prospectively identified from a tertiary University Hospital over a period of two years (2017-2019), focusing on clinical presentation, radiological patterns, outcomes and therapeutic intervention.Result
We identified a total of 23 pts with suspicion of irILD. Patients mainly received programmed cell death-1 (PD-L1) inhibitors (61%). Main characteristics are summarized in Table 1. ILD occurred more often in males, and former or current smokers (91%), with a median age of 62 years. The most common radiological pattern was the presence of ground-glass opacities (87%), followed by consolidations (61%). Forty-eight percent of the cases had grade 3 severity according to the Common Terminology Criteria for Adverse Events (CTCAE). Thirteen of the patients (57%) underwent a fibrobronchoscopy during the diagnostic period and a specific microorganism was isolated from BAL in three cases (13%) (Aspergillus fumigatus, cytomegalovirus and herpes type 1 virus). Ten pts (43%) underwent transbronchial biopsies being focal organizing pneumonia and desquamative changes the most common pathological patterns observed. Twenty patients (87%) received prednisone (1mg/kg/day) and thirteen of them (57%) also received antibiotic treatment.
Mean age (years)
61.63 ± 12.35
Type of cancer
* Others: haemathologic, bladder, liver, sigma, urothelial, timic.
* Others: Atezolizumab, Nivolumab+Ipilimumab, Atezolizumab+Daratumumab, Atezolumab+Bevacizumab, CX-072, Nivolumab/Nivolumab+Ipilipumab, Avelumab.
Immuno-mediated pulmonary toxicity is a rare but severe complication that carries a significant mortality. Due to their complexity, multidisciplinary approach is required to provide an adequate treatment and to guarantee early intervention.