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R. Matocci
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-008 - Quantification and Monitoring of Treatment Response in EGFR Mutant NSCLC Patients by Digital-PCR in Plasma cftDNA (ID 5351)
14:30 - 14:30 | Author(s): R. Matocci
- Abstract
Background:
The identification of activating epidermal growth factor receptor (EGFR) mutations is essential for deciding therapy of non-small cell lung cancer (NSCLC) patients. Circulating cell-free tumor DNA (cftDNA) holds promise as a non-invasive methodology for tumor monitoring in solid malignancies. Among advanced NSCLC patients with an acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs), about 50% carry T790M mutation, but its frequency in EGFR-TKI-naıve patients and dynamic change during therapy remains unclear. We hypothesized that EGFRmutation analysis detection in cftDNA for NSCLC may be feasible for monitoring treatment response to EGFR-TKIs and also predict drug resistance.
Methods:
EGFR sensitive mutations and T790M were analyzed using digital PCR (d-PCR) (Quant studio 3D, life technologies) in longitudinally (at baseline, at 4, 8, 20, 60, 120, 180, 270, 360 days) collected plasma samples (n=50) from 8 tissue-confirmed EGFR-mutant NSCLC patients treated with an EGFR-TKI (Gefitinib N = 4; Erlotinib N = 1; Afatinib N = 3). DNA extracted from plasma of 8 healty blood donors were used to detect the specificity of EGFR mutant assay. Tumor assessment was performed according to RECIST criteria 1.1 every two months.
Results:
The sensitivity of d-PCR in plasma versus tissue was 71.4%. No EGFR mutation was present in the 8 control cases (specificity of 100%). Of four patients who developed progression disease (PD), in the samples of progression, T790M was detected in 75% of cases. The frequency of T790M in pre-TKI plasma samples was of 37.5%. EGFR sensitive mutations decreased at PD while T790M mutation increased in 75% of patients. Patients with concomitant pre-TKI EGFR 19 deletion and T790M showed a PD before of 12 months compared to those with L858R. T790M was frequently detected when new lesions were developed. Four patients had T790M level decreased to undetectable level with longer PFS than those with detectable T790M in blood.
Conclusion:
Our results indicated that d-PCR was a highly sensitive and useful method for detecting the T790M mutation. Moreover, dynamically monitoring T790M change might help determining EGFR-TKI resistance. We thank Italian Association for Cancer Research (AIRC) for supporting the study.
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P3.02c - Poster Session with Presenters Present (ID 472)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02c-068 - Immunotherapy against Non Small Cell Lung Cancer (NSCLC): Looking for Predictive Factors to Avoid an Untargeted Shooting (ID 5207)
14:30 - 14:30 | Author(s): R. Matocci
- Abstract
Background:
The use of immunotherapy for the whole Non Small Cell Lung Cancer (NSCLC) population, is like an untargeted shooting. So trying to discover predicitve factors to response still represents the key to the problem. We retrospectively analyzed a cohort of patients (pts) treated with Nivolumab, in the attempt to correlate clinical and molecular features with response.
Methods:
69 heavily pretreated advanced NSCLCs (16 squamous/ 53 adenocarcinomas) were retrospectively evaluated for response to Nivolumab. Pts’ samples from a subgroup of responders (14/17 pts, 82%), were further analyzed for PD-L1/PD-1 expression by immunoistochemistry (IHC), and for TILs density. We used rabbit monoclonal antibodies anti PD-L1 [clone E1L3N] for tumor cell expression (0-3, negative-intense) and mouse monoclonal antibody anti PD-1 [clone EH33] for TILs.
Results:
Clinico-pathologic characteristics: mostly smoker males (81%), PS 0-1 (85%), EGFR+ 7%, K-RAS+ 23%. Overall response rate was 25% (2% complete response and 23% partial response), stable disease 30%, progressive disease 41%. Median progression free survival (PFS) and overall survival (OS) for the entire cohort were 2.9 and 8.3 months (mo) respectively. 1 and 2-y OS rates were both 44% (95% CI, 29-58). Pts with EGFR + NSCLC showed a significantly lower median OS with respect to the wild type cohort (4.5 vs NR; p < 0.005) as well as pts with brain metastases (4.1 vs NR), while a trend toward improvement in PFS for K-RAS+ was seen. A subgroup analysis according to the time to progression to prior chemotherapy regimen (< 3 mo versus > 6 mo), confirmed a poorer survival for those with rapid spread of disease. Among laboratory tests, a better outcome for those who developed G2 leucopenia was demostrated (OS 8.3 vs 5.0 mo). Severe drug-related adverse events occurred in only 5.7% of pts. PD-L1, PD-1, TIL expression for 14/17 pts with OR, were as follows: PD-L1 > 5% 6/14 pts (43%); PD-1 2/14 (14%); focal TILs presence 7/14 (50%).
Conclusion:
Nivolumab confirms activity in NSCLC with durable responses and accettable safety profile. Of note, 44% of our patients were alive at 2 years. No predictive role emerged in our small cohort, according PD-L1, PD-1 and TILs expression, for those obtaining a tumor response. Interactions among alternative factors such as smoking habit, mutational status, time to progression, bone marrow toxicities (ie leucopenia), may have more powerful association with response and clinical outcome. Updated clinical activity and biomarker analysis will be presented.
