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K. Prabhash
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MINI 10 - ALK and EGFR (ID 105)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:T. Yap, T. Li
- Coordinates: 9/07/2015, 16:45 - 18:15, Mile High Ballroom 1a-1f
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MINI10.14 - Brain Metastasis at Diagnosis and EGFR Mutational Status in Non-Small Cell Lung Cancer (ID 431)
18:00 - 18:05 | Author(s): K. Prabhash
- Abstract
- Presentation
Background:
Prior studies have indicated higher epidermal growth factor receptor (EGFR) mutation rate in non-small cell lung cancer (NSCLC) patients (pts) with brain metastases; however, these studies did not adjust for the effects of potential confounding variables.
Methods:
This was a retrospective study of NSCLC pts diagnosed between 2007-2014 at the University of Nebraska Medical Center, USA and Tata Memorial Hospital, India. After excluding 87 pts due to missing data, a total of 1522 pts were included. Univariate analysis (Chi-square or Fisher’s exact tests) and multivariate logistic regression were used to determine any association between EGFR status and clinical factors.
Results:
EGFR mutations were more common in females than males (38% vs. 24%, p<.0001), Asians than Caucasians (31% vs. 13%, p<.0001), non-smokers than smokers (40% vs. 14%, p<.0001), alcohol non-consumers than consumers (32% vs. 15%, p<.0001), adenocarcinoma than other histologies (32% vs. 10%, p<.0001) and in pts with brain metastasis than extracranial metastases or no metastasis (39% vs. 29% vs. 15%, p<.0001). The type of EGFR mutation (exon 19 vs. 21) did not correlate with the presence of brain metastasis. Multivariate analysis demonstrated a higher likelihood of an EGFR mutation among Asians vs. Whites/other ethnic groups (odds ratio, OR 2.1, p=0.015), non-smokers vs. smokers (OR 2.8, p<0.0001), alcohol non-consumers vs. consumers (OR 1.6, p=0.022) and adenocarcinoma vs. other histologies (OR 3.1, p<0.0001). Pts with brain metastasis were 1.9 times more likely to have an EFGR mutation than pts with extracranial metastasis (p=0.0002). Pts with brain metastasis were 1.8 times more likely to have an EFGR mutation (p=0.0002) compared to those without. The distribution of EGFR mutations was similar between pts with brain metastasis vs. non-metastatic disease (p=0.86) and pts with extracranial metastasis vs. non-metastatic disease (p=0.44).
Conclusion:
Our study is the largest study to demonstrate almost two-fold higher likelihood of an EFGR mutation among newly diagnosed NSCLC pts with brain metastases vs. those without. Studies of prophylactic cranial irradiation in pts with earlier stages of EGFR mutation positive NSCLC may be warranted.
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ORAL 03 - New Kinase Targets (ID 89)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:F. Blackhall, R. Juergens
- Coordinates: 9/07/2015, 10:45 - 12:15, Mile High Ballroom 4a-4f
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ORAL03.02 - Is EGFR Exon20 Mutation a Prognostic/Predictive Biomarker in Our Lung Cancer Patients? (ID 2744)
10:56 - 11:07 | Author(s): K. Prabhash
- Abstract
- Presentation
Background:
EGFR Exon20 mutations have been considered to be markers of acquired resistance to Tyrosine Kinase inhibitors. The association between Oral TKI response and Baseline Exon20 Mutations has not been addressed in many studies and remains to be evaluated.
Methods:
We conducted a retrospective audit of our prospectively maintained Lung cancer audit database in our institute in the year 2014.We reviewed data related to EGFR mutation testing by RQ-PCR using endpoint genotyping assay for EXON 20, 19, 21.We also reviewed data relating to baseline demographics,clinical profile, patient treatment and outcome measures in terms of response and survival.
Results:
We reviewed 807 sequentially tested lung cancer patients, who underwent molecular testing using RQ-PCR by endpoint genotyping assay. The overall mutation rate was 26.4% and 19 (2%) had baseline EGFR EXON20 mutation. The median age of patients was 56yrs [range: 29-81yrs], with 7 patients being females .There were 7 patients who gave past history of smoking. The most common site of metastasis was pleural effusion in 8,followed by Bone in 6,Brain in 5 and Liver metastasis in 2patients.Histology was adenocarcinoma in majority[16 patients].Among the types of EXON20 Mutations, 7 patients had S7681, 4 patients had INSGGT, 5patients had INS 9 and 4 patients had T790M mutation. All patients received chemotherapy as first line treatment. We have documented response assessment at 2months in 8 patients with progressive disease in 5[63%], stable disease in 2 and partial response in 1 patient. Second line therapy with Oral TKI was given to 9 patients, in whom we have documented response assessment in 6, all of whom had progressed.The median Overall survival of Exon-20 mutation positive patients was 5.5months. [Range of 3.8-7.2months], in comparison with other types of EGFR mutations which showed median Overall survival of 16.3months[range:12.7-19.4months
Conclusion:
EXON-20 Mutations in general proclaim grave prognosis, predicting limited benefit of chemotherapy and marked TKI resistance.
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P1.12 - Poster Session/ Community Practice (ID 232)
- Event: WCLC 2015
- Type: Poster
- Track: Community Practice
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.12-010 - Bench to Bedside Detection of Actionable Genotypes by SNaPshot for Lung Cancer Panel (ID 314)
09:30 - 09:30 | Author(s): K. Prabhash
- Abstract
Background:
Conventional therapeutic solutions in NSCLC are not effective to treat the disease. Despite of all developments in understanding of the disease, mortality of lung cancer patients remains high. Recent developments of personalized therapy have given promising results in terms of improved survival of NSCLC patients. Thus, we were keen to develop a cost effective and sensitive diagnostic lung cancer panel assay for targetable mutation detection by using SNaPShot PCR technique on FFPE samples.
Methods:
Method: Multiplexed (SNaPShot) PCR was optimized to amplify hotspot regions from 9 targetable genes followed by single base extension reaction using fragment analysis on ABI 3500 Sequencer. Gene Mapper software was used for analysis
Results:
The successfully developed mutation profiling assay was divided into 3 multiplexed reactions, covering 23 actionable genotypes of EGFR, KRAS, BRAF, PIK3CA, Her2, AKT1, NRAS, MEK1 and PTEN genes. The assay was standardized and validated on 20 blood samples, 10 cell lines and 20 FFPE samples expressing good sensitivity and specificity for wild type and mutant genotypes.
Conclusion:
This In house developed SNaPShot PCR technology is robust, economical, specific and sensitive to detect actionable mutations in FFPE Adeno as well as in Squamous Carcinoma samples. Because these variants have differing genetic, biological, and clinical properties, including response to treatment, this Bench to Bedside research will lead us to correct classification of lung cancer cases and will assure that lung cancer patients receive optimum management.
