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Tiziana Vavalà
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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
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P1.14-04 - Final Results of the Prospective Genomics of Young Lung Cancer (GYLC), an Addario Lung Cancer Medical Institute Study (ID 427)
09:45 - 18:00 | Author(s): Tiziana Vavalà
- Abstract
Background
We hypothesized that young age at lung cancer diagnosis is a clinical characteristic associated with a higher likelihood for having a driver mutation. Our goals were to identify a genomically enriched subtype of lung cancer, facilitate delivery of targeted therapy and lay groundwork for studies of heritable and environmental lung cancer risk factors.
Method
Eligible subjects had a diagnosis of bronchogenic lung cancer < 40 years old. We included a website to allow for virtual consenting and remote participation from anywhere in the world. An integrated data and biorepository allowed for completion of study activities and routing of specimens. We defined seven genes of interest based on the Lung Cancer Mutational Consortium (LCMC): EGFR, KRAS, HER2, BRAF, ALK, ROS1, RET. We hypothesized that the prevalence of targetable alterations in these genes would be greater in our population compared to the LCMC and powered our study to detect an increase from 35% to 50%. Subjects with advanced adenocarcinoma who were not tested for all seven genes or who were wild type for all seven underwent additional genomic profiling using Foundation Medicine testing.
Result
We accrued 133 participants from July 2014 to June 2017. Notably, 44% entered the trial via the website. The mean age at diagnosis was 34 (range 16 to 39) and 57% were female; 77% were stage 4 at diagnosis and the majority had adenocarcinoma (86%). Of the 115 patients with adenocarcinoma, 83.5% were stage 4 and the focus of the comparison to the LCMC cohort. A targetable mutation was identified in 85.4%, with 76% harboring a combined ALK (38.5%), EGFR (31.3%), or ROS1 (6.3%) mutation. Of 14 patients who underwent on-protocol testing, a targetable driver was identified in eight (57%), including two with a RET rearrangement, two with ERBB2 mutations, two with MET amplification, one with an ALK rearrangement with a prior negative FISH and one with a novel EGFR-RAD fusion previously tested negative for EGFR.
Conclusion
We have described a genomically distinct subset of NSCLC in patients < age 40. Those with stage 4 adenocarcinoma must undergo comprehensive genomic testing to identify a targetable driver. The extremely high rate of driver mutations particularly in ALK supports the need for an Epidemiology of YLC study. Additionally, use of remote consenting and the Addario Lung Cancer Foundation's advocacy enabled rapid accrual of this rare cohort (<1%) and has laid the foundation for innovative research partnerships with other rare oncogene-driven patient groups.
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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
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P2.04-14 - NLR, dNLR and PLR as Possible Predictive Markers in Patients with NSCLC Treated with ICI (ID 1063)
10:15 - 18:15 | Presenting Author(s): Tiziana Vavalà
- Abstract
Background
Clinical evidence suggests a possible predictive role of Neutrophil-to-Lymphocyte ratio (NLR), derived Neutrophils/(leukocytes minus neutrophils) ratio (dNLR) and Platelet-to-Lymphocyte ratio (PLR) in different tumors, including non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI).
Method
In this Italian multicenter retrospective trial NLR, dLNR, PRL fluctuations were analyzed in patients with stage IV NSCLC treated with ICI. Those rates were assessed at baseline, before the second, third and fifth cycles. In patients still on treatment, samples were collected also at 1 and at 2 years from ICI start. The primary objective was the relationship between baseline ratios and response to ICI, through the identification of different cut-offs estimated using ROC curves.
Result
Data of 402 patients receiving ICI (antiPD1 91%, antiPDL1 7% and antiPDL1 plus antiCTLA-4 2%) were analysed: 287 (71%) were males, median age was 65 (39-86 yrs-old), 84 patients (21%) were on first line treatment. The most common histology was adenocarcinoma (62%) and 95% of patients had an ECOG performance status of 0-1. One hundred and eleven (30%) patients were using steroids in permissive doses for ICI. Disease control rate (DCR) was observed in 228 patients (58%) with 95 (24%) reporting an immune objective response. Median progression free survival was 5,3 months and the median overall survival was 9,6 months, after a median follow-up of 9,6 months (range 4,0-13.0). Basal NLR, dNLR and PRL were predictive of response (p=0.0002, p=0.0003 and p=0.0304, respectively). Best response categories were dichotomized in Response (SD + PR + CR) versus no Response (PD). With this classification, the differences were more pronounced and statistically significant for basal NLR and dNLR (p=0,045 and p=0,004, respectively). The cut-off values for basal NLR and dNLR were defined (BLNLR=2,46; BLdNLR=1,61) to identify patients most at risk of “non Response” through the ROC curves. Confounding factors were assessed using logistic regression models (age, gender, smoking). During treatment, an increase in the values was observed at the time of progression, both for NLR (average variation: -1.57) and for dNLR (average variation + 0.32), even if the statistical significance is limited to NLR (p = 0.041).
Conclusion
NLR, dNLR and PLR are independent factors of response to ICI. Compared to the present literature data, this study highlights that NLR ratio may predict progressive disease earlier than radiological restaging.
