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M. Serke
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P1.07 - Poster Session with Presenters Present (ID 459)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.07-003 - A Phase II Study Evaluating the Combination of Everolimus with Carboplatin/Paclitaxel as 1st Line Treatment in Patients with Advanced LCNEC (ID 4370)
14:30 - 14:30 | Author(s): M. Serke
- Abstract
Background:
Approximately 3% of all lung cancers are made up of large cell neuroendocrine carcinoma of the lung (LCNEC). These tumors in general have a bad prognosis and currently there are only very limited treatment options, including platinum derivatives and etoposide. The PI3/AKT/mTOR pathway is known to be dysregulated in neuroendocrine tumors (NETs). Since the mTOR inhibitor RAD001 (everolimus) already has proven effectiveness in different types of NETs, we tested whether everolimus might be also an effective treatment option in advanced LCNEC patients.
Methods:
In this multi-center, open-label, phase II study, everolimus was combined with platin-based chemotherapy in patients with histologically confirmed stage IV LCNEC according to WHO criteria. Further inclusion criteria were measurable disease according to RECIST 1.1 and adequate bone marrow, renal, and liver function. Main exclusion criteria were symptomatic CNS metastases and prior treatment for advanced LCNEC. Enrolled patients received everolimus once a day in combination with 4 cycles of carboplatin and paclitaxel, followed by daily everolimus maintenance therapy. The primary objective was to evaluate the efficacy by assessing the proportion of progression-free patients after three months of treatment.
Results:
Ten German trial sites enrolled altogether 49 patients (mean age: 62 ± 9 years; 71% men). The primary endpoint (proportion of pts progression-free at month 3) was achieved by 24 patients (49%), assessed by an independent central imaging reviewer. Further efficacy evaluation showed an overall response rate (ORR) until month 3 of 45%, a disease control rate (DCR) until month 3 of 73.5%, a median progression-free survival (PFS) of 4.3 months, and a median overall survival (OS) of 9.8 months. At least one toxicity occurred in 86% of all enrolled patients with grade 3/4 toxicities in 51%. Most frequent toxicities were diarrhea, fatigue, anemia, and neutropenia.
Conclusion:
The results show that a combined therapy of carboplatin and paclitaxel with the mTOR inhibitor everolimus is an alternative treatment option for LCNEC patients. When comparing to other trials, the effectiveness is comparable to a treatment regimen of cisplatin and etoposide.
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-036 - Analysis of Potentially Targetable Mutations in 821 Patients with Squamouscell Lung Cancer Undergoing Routine NGS-Based Molecular Diagnostics (ID 5939)
14:30 - 14:30 | Author(s): M. Serke
- Abstract
Background:
Molecular multiplex diagnostics is increasingly integrated now in routine diagnostics of lung adenocarcinoma (LAD). Although targetable aberrations are predominantly found in LAD, they have also been reported in squamouscell lung carcinoma (SQLC). We here present results of routine molecular multiplex diagnostics of advanced stage SQLC obtained within the German Network Genomic Medicine (NGM) and compare them with results reported previously in early stage SQLC in The Cancer Genome Atlas (TCGA) LUSC cohort.
Methods:
Tumor biopsies of 821 patients consecutively diagnosed within NGM were analyzed with next-generation parallel sequencing (NGS). The panel consisted of 102 amplicons and 14 genes: KRAS, PIK3CA, BRAF, EGFR, ERBB2, NRAS, DDR2, TP53, ALK, CTNNB1, MET, AKT1, PTEN and MAP2K1. In subsets of patients, fluorescence in-situ hybridization (FISH) was performed for amplification detection of FGFR1 and MET. We queried the TCGA dataset with respect to the panel used and compared the findings. For NGM patients, therapy and outcome are also reported..
Results:
In addition to the expected frequencies of TP53, DDR2, PTEN and PIK3CA mutations, we detected EGFR mutations in 3.2% and BRAF mutations in 1.8%. Unlike the TCGA dataset, where the frequencies were 2.8% and 3.9%, respectively, the detected mutations in the NGM cohort included also activating targetable mutations (i. e., EGFR del19 and L858R, and BRAF V600E). FISH data revealed presence of MET amplification in 14.2% and of FGFR1 amplification in 20.0%. The association and correlation of these aberrations with clinical findings and prognosis as well as with PD-L1 expression status and mutational load will be presented.
Conclusion:
Our data give an overview on the presence and clinical characteristics of targetable mutations in advanced SQLC and show, that such mutations occur in a substantial amount of patients. Thus, molecular multiplex diagnostics might be indicated also in SQLC in order to use all therapeutic options available in these patients.
