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Daniel Sumarriva
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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
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.01-88 - Next-Generation Sequencing in Hispanic Patients with Advanced Lung Cancer and Correlation with Response to Immunotherapy (Now Available) (ID 2784)
08:00 - 18:00 | Author(s): Daniel Sumarriva
- Abstract
Background
Cancer is a leading cause of death among Hispanics (HISP); the largest ethnic minority in the United States (17% of the total population). With the approvals of checkpoint immunotherapy in advanced lung cancer, many patients (pts) are starting to see long-lasting remissions and longer survival rates. However, response to a given treatment often depends on the tumor’s genomic profile. Our aim was to analyze NGS results for HISP pts living in the US in an effort to better understand this population’s genomic profile and prognosis.
Method
Retrospective analysis on pts with biopsy proven advanced NSCLC who received checkpoint immunotherapy at two large institutions in the US. Patient charts were reviewed to obtain data on demographic characteristics including race, gender, age, and smoking history. Next generation sequencing (NGS) results were obtained from Guardant Health and Foundation One testing in blood and in tissue, respectively. We assessed progression-free survival (PFS) and overall survival (OS) associated with outcome.
Result
Seventy HISP pts receiving immunotherapy underwent NGS testing from 10/2013 to 4/2018. 46% were male, 76% were smokers, 89% had adenocarcinoma, and 39% were PD-L1 positive (with 67% of those having TPS ≥ 50%). Thirty pts (43%) had one genetic aberration (GA), and 15 pts (22%) had >5 GA. The most frequent actionable GA was EGFR mutation (26%) and nonactionable mutation was KRAS (40%). Other less common GA were BRAF (10%), MET (10%), and STK11 (9%).
Survival
1 Genetic Aberration
>5 Genetic Aberrations
P value
Median PFS
3.57m
3m
0.2767
Median OS
14.96m
3.8m
0.0117
Conclusion
The presence of >5 GA (actionable and nonactionable) on NGS testing was associated with worse OS when compared to pts with one GA. There was no difference in PFS. In addition, PD-L1 incidence in HISP pts is high with a larger proportion of pts expressing ≥ 50% TPS compared to what is reported for NHW. Given the numerous nonactionable GA encountered, it is clear that continued development of targeted therapies would keep benefitting pts. Increased NGS profiling in HISP pts could potentially broaden treatment and clinical trial options to serve this purpose.
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-68 - Monitoring Clinical Responses Measuring PD-L1 in cfRNA in Plasma of Non-Small Cell Lung Cancer Patients Undergoing Systemic Therapy (Now Available) (ID 2356)
09:45 - 18:00 | Author(s): Daniel Sumarriva
- Abstract
Background
.Cell-free circulating tumor RNA (cfRNA) extracted from plasma of cancer patients (pts) can measure dynamic changes in gene expression that can help to evaluated disease status and predict outcome to anti-tumoral therapy in solid tumors [T. Ishiba et al. Biochem Biophys Res Commun. 2018 Jun 7; 500 (3):621-625]. We want to show that PD-L1 assessed by RNA RT-PCR is a potential biomarker that can be used to follow Immunotherapy responses in non-small cell lung cancer (NSCLC).
Method
54 pts with NSCLC undergoing systemic therapy (STX) were enrolled in a 1-year study. cfRNA was extracted from resulting plasma and generated random-primed cDNA. Total cfRNA was quantitated by qPCR of β-actin, and correlated with pt response (CR/PR/SD/PD) determined by CT scans. All gene expressions were measured relative to β-actin. Changes in PD-L1 expression were used to monitor response to immunotherapy in lung cancer pts. Ten milliliters of blood were collected in each of two tubes containing a proprietary nucleic acid preservation cocktail. Blood was drawn every 6-8 weeks with an average of 5 collections were done per pt.
Result
Of the 54 enrolled pts, 30 completed 1-3 lines of STX with outcomes. The overall mutation frequency was 33% (10/30), with 27% in KRAS and 6% in EGFR. Increases or emergence of mutant allele fractions were predictive of PD status (later determined by imaging), while decreases or disappearance of mutations were predictive of SD and PR status after treatment. PD-L1 expression was detected in 87% (26/30) of pts in at least one blood draw.
Immunotherapy: (Nivolumab, Pembrolizumab, Atezolizumab), 11/30 pts underwent immunotherapy (IO) txt at some point. Changes in PD-L1 during IO were associated with STX outcomes. Increases in PD-L1 were associated with PD, while decreases or no changes in PD-L1 were associated with SD and PR. Of the 23 blood draws from these 11 pts, the overall concordance between changes in PD-L1 and IO outcome was 91% (21/23). Chemotherapy: 19/30 pts were given carbo/pemetrexed at some point during their STX. Increases or decreases in PD-L1 across 28 blood draws during therapy were likewise associated with resistance or sensitivity to STX outcome (increases infer resistance; decreases infer sensitivity) in 24/28 (86%).
Conclusion
A noteworthy concordance was observed between clinical responses and changes in plasma PD-L1 done by RT-PCR cfRNA levels in NSCLC pts treated with IO or chemotherapy. Monitoring cfRNA expression levels of PD-L1 is a reliable method for predicting response and resistance to IO as well as chemotherapy irrespective of KRAS and EGFR
