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M. Pesek
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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. Pesek
- 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: 2
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.01-019 - Czech Experience with Crizotinib in the Personalized Treatment of NSCLC (ID 305)
09:30 - 09:30 | Author(s): M. Pesek
- Abstract
Background:
Crizotinib is a highly selective drug used in the treatment of anaplastic lymphoma kinase (ALK) gene re-arrangement positive non-small cell lung cancer (NSCLC). In the Czech Republic it was used in frame of compassionate cases program and now is reimbursed in pretreated tumors with EML 4/ALK gen translocation verified by FISH and/or IHC testing. The recommended dose is 250 mg bid/ day. Crizotinib is used since 2011, data are evaluated according to the National Reference Centre Registry.
Methods:
Present study evaluates 26 patients (pts), 14 males,12 females with mean age 60 (31- 75) years. Out of them 11 (42.3%) were non-smokers, 8 (30.8%) ex-smokers and 7 (26.9 %) smokers. All of them had NSCLC with EML4/ALK gene translocation, 23 had adenocarcinoma, two NOS and one patient had adenosquamous cancer. Stage in the time of treatment was IIIB in 3 and IV in 23 pts. Crizotinib was applied in 2[nd] ĺine in 17 pts, 3[rd] line in 5 pts, 4[th] line in 3 pts, 5[th] in one patient. PS was 0 in 3 pts, 1 in 20 pts and 2 in 3 pts.
Results:
On the date of evaluation, 14 pts continued the treatment, 6 died and 6 stopped treatment due to progression. Crizotinib effectiveness was assessed in 15 pts: CR in 3 (20%) pts, PR in 3 (20%) pts, SD in 5 (33.3 %) pts, DP in 4 (26.7 %) pts. CR was associated with long response duration (10.7, 31.8, 34.1 months). Grade 3 adverse events (gastrointenstinal discomfort and liver disease) were observed in two (7.7 %) pts, grade 2 problems with visus appeared in two patients. Dose of crizotinib was reduced in 3 pts. Median of progression free survival was 15 months, median of overall survival was not reached.
Conclusion:
Interim analysis of present series shows, that crizotinib has very good tolerability and promising effectiveness even in heavily pretreated patients with EML4/ALK gene translocation. Long term survival analysis is running. Supported by national grant IGA MZ ČR NT/13569
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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. Pesek
- 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: 2
- 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. Pesek
- 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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P2.01-071 - TULUNG REGISTRY: Data Analysis of Patients with Non-Squamous NSCLC Treated with Bevacizumab in the Czech Republic (ID 2934)
09:30 - 09:30 | Author(s): M. Pesek
- Abstract
Background:
We conducted a systematic review of data from patients reported in the TULUNG registry (data cut-off 26-Jan-15). The TULUNG registry is Czech national oncology registry which prospectively collects data from all NSCLC patients treated with new targeted therapies in Czech Republic since 2008.
Methods:
Analysis was performed on a group of patients with non-squamous NSCLC with good performance status (PS 0-2), treated with bevacizumab. Since 2008 bevacizumab has been used for treatment in 193 patients (full record criteria met). 10 patients with incomplete records were not included to the review
Results:
In this group of patients 35.8% were female; the median age at bevacizumab treatment initiation was 60 years (range 29-83). The majority of patients were smokers and ex-smokers (37.8% and 34.7% respectively) and 91.7% of tumors were adenocarcinomas by histology. 91.7% patients were at the metastatic stage at the initiation of bevacizumab treatment, 6.2% of patients were in stage IIIb and only 2.1% of patients in stage IIIa (UICC6). The performance status was distributed between ECOG PS0 and PS1 mainly (40.9% PS0 and 58% PS1)at the initiation of the bevacizumab treatment. Majority of patients received bevacizumab treatment in the first line (96.4%). Two main chemotherapy regimens were used; carboplatin+paclitaxel (68.4%) and cisplatin+gemcitabine (9.8%). In this group of 193 patients analyzed, bevacizumab therapy was terminated in 152 (78.8%) patients at data cut-off. The most frequent reasons for termination were disease progression, in 55.9%, termination of treatment according to plan in 8.6% and death, in 7.9% of patients. Treatment with bevacizumab is ongoing in 41 (21.2%) patients. In 152 of patients with terminated treatment, the median duration of treatment was 15.6 weeks (95% CI 0.3 – 51.3). Response assessment showed CR in 0.7%, PR in 40.8% and SD in 35.5% of patients. Median progression free survival was 6.9 months (95% CI 5.8 – 8.1), median overall survival 16.7 months (95% CI 11.7 – 21.7). 1-year survival from bevacizumab treatment initiation was 67.9%. Adverse events were reported in 9.8% of patients, the most frequently reported adverse events were thromboembolic events (5.2%) and neutropenia (1.6%). Tromboembolic events were observed in 10 patients, none of these was fatal. We didn´t observe any severe episode of bleeding event.
Conclusion:
Therapy with bevacizumab in non-squamous NSCLC was active and very well tolerated. In eligible patients, only 7 patients (4.6%) had to discontinue bevacizumab therapy due to safety reasons. In patients with completed bevacizumab therapy 77.0% disease control rate was reached with a median survival of approximately 16.7 months from initiation of first line therapy with bevacizumab.
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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: 3
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-008 - Gefitinib in Front-Line Treatment of 161 Caucasian Patients with NSCLC of the Czech Republic (ID 424)
09:30 - 09:30 | Author(s): M. Pesek
- Abstract
Background:
Gefitinib is a potent oral non-cytotoxic, active and selective epidermal growth factor receptor tyrosine kinase inhibitor. This study evaluates treatment outcomes in 161 NSCLC patients from Czech Republic according to activated mutations located in exons 19 and 21.
Methods:
Data treated patients with gefitinib are collected in the TULUNG registry, which is a common project of the Czech Pneumological Society, Czech Oncological Society, and Institute Biostatistics and Analyses Masaryk University Brno. NSCLC patients with EGFR activated mutations were treated in first line between 02/2010 and 12/2014 in 10 institutions. Retrospective analyses were carried out to assess the effectiveness and safety of gefitinib treatment according to activated mutations located in exons 19 and 21. The analysed outcomes include following: treatment response rate, median Overall Survival (mOS), median Progression Free Survival (mPFS) and occurrence of types adverse events.
Results:
Out of 161 treated patients, 105 (70 female, 35 male) had EGFR mutations in exon 19, and 56 (39 female, 17 male) had EGFR mutations in exon 21. Median age was 66 years in the group with mutations in exon 19 and 69 years in the group with mutations in exon 21. There was no statistically significant difference in sex (p=0.727) and in age (p=0.204). No statistically significant difference was observed in the representation in smoking (p=0.354). There was statistically borderline significant difference in adenocarcinoma proportion (p=0.045). In the group with mutations in exon 19 were 96% patients with adenocarcinoma and in the group with mutations in exon 21 were 85% patients with adenocarcinoma. Between these two groups, there was no statistically significant difference according to performance status (p=0.547); no statistically significant difference according to disease control (CR+PR+SD) (p=0.479); no statistically significant difference according the response to the treatment (CR + PR) (p=0.052). There was no statistically significant difference in mOS (p=0.390). In the group of patients with mutations located in exon 19, the overall survival was 22.7 months (CI 95%: 17.7; 27.8), in the group with mutations in exon 21, overall survival was 16.3 months (CI 95%: 10.8; 21.8). There was no statistically significant difference (p=0.202) in mPFS; in the group of patients with mutations in exon 19 it was 11,0 months (CI 95%:9.1; 12.8) and in the group with mutations in exon 21 it was 9.4 months (CI 95% 6.6; 12.2). SimiIar numbers of adverse effects were observed in either group (35.2% and 35.7%). Almost 70% of patients with mutations in exon 19 and almost 60% of patients with mutations in exon 21 are still alive or were lost to follow up. These patients are censored to the date of last update.
Conclusion:
In both groups of patients, the treatment was very safe. Median PFS and median OS were satisfactory without statistically significant differences between the two groups; however, a better trend was observed in the group of patients with mutations in exon 19. Consequently survival estimates shows great variability and longer potential follow up is needed to confirm these results.
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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. Pesek
- 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. Pesek
- 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.
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P3.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 226)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.08-010 - Pemetrexed and Cisplatin in Malignant Pleural Mesothelioma - Czech Experience (ID 213)
09:30 - 09:30 | Author(s): M. Pesek
- Abstract
Background:
Malignant Pleural Mesotelioma (MPM) is a tumour with extremely unfavourable prognosis. Early diagnostic is rarely possible and chemotherapy has limited value in prolongation of survival. Pemetrexed with platinum is the standard 1[st] line chemotherapy. In the Czech Republic, the incidence of MPM is influenced mostly by former industry processing asbestos for roofs, other parts of buildings and isolation materials. Any work with asbetos is prohibited in the mean time.
Methods:
Treatment with pemetrexed and cisplatin was evaluated in a prospective study. Data of consecutive patients from 9 centers were prospectively collected from January 2008 till February 2015. Altogether 181 patients (47 women, 134 men) were evaluated. Mean age was 62 years, 71 pts were non smokers, 47 smokers, 61 ex smokers. Professional/ non-professional exposure was reported in 44/ 18 pts. Histology: 119 epithelial, 20 mixed, 12 sarcomatoid, not specified in 30 pts, TNM st.: I/II/III/IV in 19/32/48/78 pts, not assessed in 4 pts, PS: 0/1/2 in 39/130/12 pts.
Results:
Median of treatment was 18.5 weeks. Most frequent side effects (Gr 3, 4): leucopenia in 22, neutropenia in 15, anaemia in 15, trombocytopenia in 6, nausea/vomiting in 19, fatigue in 8 pts. Therapeutic response: CR in 5, PR in 47, SD 85, PD in 21 pts, overall disease control was 75.6 %. The median of overall survival (OS) was 19.8 months (16.2; 23.4), 1 year survival 67.9% (48.3; 71.5). Median of progression free survival (PFS) was 9.1 months (7.6; 10.7). Differences of survival were compared according to sex, smoking history, age, PS, TNM stage, treatment associated AE occurrence, type of exposure and histology. Significantly different results were achieved according to PS,TNM, exposure, AE and histology.
Conclusion:
Treatment of MPM with pemetrexed and cisplatinum in routine practice is effective and well tolerated. Prognosis is still poor and it is influenced by several clinical markers. Longer survival can be expected in PS 0, TNM I/II, unknown asbestos exposure, epitheloid histology and no treatment associated AE. Supported by national grant IGA MZ ČR NT/13569
