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M. Minarik
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MINI 16 - EGFR Mutant Lung Cancer 2 (ID 130)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:G.J. Riely, M.C. Garassino
- Coordinates: 9/08/2015, 16:45 - 18:15, Four Seasons Ballroom F3+F4
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MINI16.02 - Rare and Common EGFR Mutations in Patients with Advanced NSCLC Treated with EGFR-TKIs: A Registry-Based Study (ID 2775)
16:50 - 16:55 | Author(s): M. Minarik
- Abstract
- Presentation
Background:
Erlotinib, gefitinib and afatinib, tyrosine kinase inhibitors directed at EGFR signalling (EGFR-TKI), are currently used for the treatment of patients with advanced-stage non-small cell lung cancer (NSCLC). A considerable progress in the field of molecular oncology and cancer genomics in recent years has let to identification of several gene alterations predicting clinical outcome of patients treated with EGFR-TKIs. Activating EGFR mutations are widely recognized predictors of good response to EGFR-TKI treatment. While the predictive role of common EGFR mutations (exon 19 deletions and exon 21 L858R point mutation) is well described, very little clinical evidence data exist on the role of rare EGFR mutation types. The aim of this study was to assess the distribution of common and rare EGFR mutations in patients with NSCLC and to evaluate the efficacy of EGFR-TKIs for patients harboring rare and common EGFR mutations.
Methods:
Clinical data of 305 patients with advanced-stage NSCLC (IIIB or IV) treated with EGFR-TKIs having EGFR mutation positive primary tumors at the time of diagnosis were evaluated in a retrospective setting. The therapy included erlotinib, gefitinib or afatinib as recorded in a Czech national lung cancer registry – TULUNG. The relative frequency and survival data (PFS and OS) were evaluated for individual EGFR mutation types.
Results:
The common activating EGFR mutations (exon 19 deletion and exon 21 L858R point mutation) were found in a total of 249 (81.6%) patients. Rare EGFR mutations were found in 56 (18.4%) patients, the most frequent of which was exon 18 - G719X mutation found in 29 patients (9.5%), followed by mutations in exon 20 found in 28 patients S768I in 3 patients (0.98%) and insertion 3 mutations in 16 patients (5.2%). Patients with exon 19 deletion had median median OS 11.0 months, patients with exon 21 point mutation L858R median OS 9.4 months,respectively. Patients with rare EGFR mutations median OS 12.5 months.Comparing frequent and rare mutations, there were no differences in sex, age, PS, stage of disease and adverse effects of first line gefitinib therapy, the group of patients with rare mutations were more frequently smokers, duration of gefitinib therapy was shorter, response rate and PCR, PFS and OS were worse than in patients having frequent EGFR mutations. There were no significant differences in characteristics, PFS and OS between exon 19 deletion and exon 21 L858R point mutation tumour patients.
Conclusion:
While patients with frequent EGFR sensitive mutations have significant benefit from gefitinib therapy, patients with G719X mutation on exon 18 have marginal PFS and OS benefit, while pagtients with exon 20 insertion mutations have no demonstrable benefit from targeted therapy.Next generation tyrosinkinase inhibitors may prolong survival in some of rare EGFR mutated tumour patients.
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P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.01-067 - Epidermal Growth Factor Receptor Gene Amplification in Patients with Advanced-Stage NSCLC (ID 2665)
09:30 - 09:30 | Author(s): M. Minarik
- Abstract
Background:
Tyrozine kinase inhibitors (TKI) targeting epidermal growth factor receptor (EGFR) represent a novel effective tools in management of advanced-stage non-small cell lung cancer (NSCLC). We aimed to evaluate the incidence and predictive role of EGFR gene amplification in patients with advanced-stage NSCLC treated with EGFR-TKIs.
Methods:
The study included 290 patients with advanced-stage (IIIB or IV) NSCLC. Multiplex ligation-dependent probe amplification (MLPA) and Polymerase chain reaction (PCR) were used for detection of EGFR mutations and EGFR gene amplification, respectively.
Results:
EGFR amplification was detected in 26 (9.0%) patients. EGFR amplification was found more frequent in patients harboring EGFR mutation (p < 0.001). No significant corelation between EGFR gene amplification and survival was observed.
Conclusion:
The presence of EGFR gene amplification is associated with EGFR gene mutations. EGFR gene amplification is not a feasible predictive biomarker for the treatment with EGFR-TKIs in patients with advanced-stage NSCLC. This study is supported by Ministry of Health, Czech Republic - conceptual development of research organization Faculty Hospital in Pilsen - FNPl, 00669806 and by the project CZ.1.05/2.1.00/03.0076 from European Regional Development Fund.
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-070 - Serum Albumin in Patients with Advanced-Stage NSCLC Treated with Erlotinib (ID 2676)
09:30 - 09:30 | Author(s): M. Minarik
- Abstract
Background:
Molecular targeted therapy based on tyrozine kinase inhibitors (TKI), directed at epidermal growth factor receptor (EGFR) is one of the novel effective agents in management of advanced-stage NSCLC. However several candidate predictors have been extensively studied, apart from activating EGFR gene mutations, no reliable biochemical or molecular predictors of response to erlotinib have been validated. The aim of our retrospective study was to evaluate the association of baseline serum albumin with outcomes in a large cohort of patients with advanced-stage NSCLC treated with erlotinib.
Methods:
Clinical data of 457 patients with locally-advanced (IIIB) or metastatic stage (IV) NSCLC treated with erlotinib were analysed. Serum samples were collected and the measurement was performed one day before the initiation of erlotinib treatment.
Results:
Before the treatment initiation, low albumin was (<35 g/l) measured in 37 (8.1%) patients and normal albumin (≥ 35 g/l) was measured in 420 (91.9%). The median PFS and OS for patients with low serum albumin was 0.9 and 1.9 months compared to 1.9 and 11.4 months for patients with normal serum albumin (p=0.001 and p<0.001). The multivariate Cox proportional hazards model revealed that EGFR mutation status (HR=2.50; CI: 1.59-3.92; p<0.001) and pretreatment serum albumin (HR=1.73; CI: 1.21-2.47; p=0.003) were significant independent predictive factors for PFS, whereas EGFR mutation status (HR=3.14; CI: 1.70-5.81; p<0.001), stage (HR=1.48; CI: 1.09-2.02; p=0.013), ECOG PS (HR=1.77; CI: 1.37-2.29; p<0.001) and pretreatment serum albumin (HR=4.60; CI: 2.98-7.10; p<0.001) were significant independent predictive factors for OS.
Conclusion:
The results of the present retrospective study indicate that pretreatment hypoalbuminemia is associated with poor outcome of NSCLC patients treated with erlotinib. Based on the present study results, measuement of serum albumin is an objective laboratory method feasible for estimation of prognosis of patients with advanced-stage NSCLC. This study is supported by Ministry of Health, Czech Republic - conceptual development of research organization Faculty Hospital in Pilsen - FNPl, 00669806 and by the project CZ.1.05/2.1.00/03.0076 from European Regional Development Fund.
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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-021 - New Perspectives for the Patients with ALK Positive Lung Adenocarcinomas, after Failure of Crizotinib Therapy. A Single Institution Experience (ID 2801)
09:30 - 09:30 | Author(s): M. Minarik
- Abstract
Background:
Patients suffering from ALK-rearranged non-small cell lung cancer (NSCLC) should have significant benefit of ALK inhibitor targeted therapy by crizotinib. Even if high frequency of response rate to this therapy is documented, wast majority of those tumors become resistent due to overgrow of secondary resistent mutations bearing tumour cells. Such resistence should be overcome with the help of an alternative second generation ALK inhibitors.
Methods:
We present our diagnostic and therapeutic single institution experience in patients having ALK-rearranged NSCLC, as examined by FISH. We also present two case reports of patients treated by a second generation ALK inhibitor (ceritinib) after failure of the initial crizotinib therapy.
Results:
Between January 2011 and January 2015, a total of 595 tumour tissue samples were prospectively analysed for a presence of ALK rearrangements. A conclusive FISH result was obtained from a subset of 483. ALK rearranement was found in 15 patients (3.1%). The group consisted of 9 males and 6 females, with a median age of 65. 13 of the tumours were adenocarcinomas, 2 adenosquamous carcinomas. 8 patients were nonsmokers, seven were smokers. Consequently, 6 patients were treated by crizotinib while the rest did show a rapidly progressing tumours. 3 of the 6 crisotinib patients had a documented benefit from the therapy lasting for 22, 15 and 6 months.Finally, after failure of crizotinib, 2 patients reached a second partial remission on ceritinib,lasting 9 and 6 months.
Conclusion:
Targeted therapy of ALK-positive tumours is capable to prolong survival of patients quite significantly. In crizotinib - resistent tumours, second generation ALK inhibitors (such as ceritinib in this case), maybring further benefits to patients.
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P3.01-028 - Serum Levels of C-Reactive Protein Predict Poor Outcome of Patients with Advanced-Stage NSCLC Treated with Erlotinib (ID 2614)
09:30 - 09:30 | Author(s): M. Minarik
- Abstract
Background:
Erlotinib is a low-molecular weight tyrosine kinase inhibitor (TKI) directed at epidermal growth factor receptor (EGFR), widely used in the treatment of locally-advanced or metastatic stage NSCLC. Although introduction of EGFR-TKIs have significantly extended survival of advanced-stage NSCLC patients, their efficacy in the entire patient population is relatively low, especially in Caucasians. Aside from activating EGFR gene mutations, no reliable biochemical or molecular predictors of response to erlotinib have been established. The aim of our retrospective study was to evaluate the association of baseline serum levels of C-reactive protein (CRP) with outcomes in patients with advanced-stage NSCLC treated with erlotinib.
Methods:
We retrospectively analysed clinical data of 595 patients with advanced-stage NSCLC (IIIB or IV) treated with erlotinib. Serum CRP was measured using immunoturbidimetric method.
Results:
Before the treatment initiation, high baseline levels of CRP (≥ 10 mg/l) were measured in 387 (65%) patients and normal levels (< 10 mg/l) were measured in 208 (35%) patients. The median PFS and OS for patients with high CRP was 1.8 and 7.7 compared to 2.8 and 14.4 months for patients with low CRP (p<0.001 and p<0.001). The multivariate Cox proportional hazards model revealed that CRP (HR=1.57, p<0.001), EGFR status (HR=2.22, p<0.001), stage (HR=1.31, p=0.013) and ECOG PS (HR=1.22, p=0.024) were significantly associated with PFS and also with OS (HR=1.63, p<0.001; HR= 1.97, p=0.011; HR=1.44; p=0.007 and HR=1.72, p<0.001, respectively).
Conclusion:
The results of the conducted retrospective study suggest that the baseline level of CRP was independently associated with PFS and also with OS. CRP is commonly used biomarker which is simple and easy to detect and thus it is feasible for the use in the routine clinical practice. This study is supported by Ministry of Health, Czech Republic - conceptual development of research organization Faculty Hospital in Pilsen - FNPl, 00669806 and by the project CZ.1.05/2.1.00/03.0076 from European Regional Development Fund.
