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V. Kolek
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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): V. Kolek
- 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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ORAL 04 - Adjuvant Therapy for Early Stage Lung Cancer (ID 99)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:E. Vallieres, Y. Ohe
- Coordinates: 9/07/2015, 10:45 - 12:15, 205+207
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ORAL04.07 - Adjuvant Chemotherapy in Patients with Resected Non-Small-Cell-Lung Cancer Treated with Carboplatin and Oral Vinorelbine - SWITCH I Study (ID 497)
11:50 - 12:01 | Author(s): V. Kolek
- Abstract
- Presentation
Background:
Adjuvant cisplatinum-based chemotherapy is recommended in patients with stages IB (≥ 4 cm), IIA, IIB, and IIIA of non small-cell lung cancer (NSCLC) after radical resection. Vinorelbine with cisplatin are preferable drugs in this indication, but the side effects of this treatment were not negligible in big adjuvant trials. Carboplatin with vinorelbine given intravenously switched to orally were applied in a multicentre prospective study SWITCH I to give better comfort, higher tolerability and comparable effectivenes as standard adjuvant chemotherapy. The recruitment period started in January 12[th], 2005 and lasted till September 5[th], 2008.
Methods:
Consecutive chemo-naive patients were recruited after complete resection of NSCLC stages IB, IIA, IIB and IIIA. Chemotherapy was applied from 2 to 6 weeks after complete resection. Four cycles of 21 days regimens were planned, Patients received carboplatin AUC 5 on the day 1,vinorelbine 25 mg/m[2] intravenously on the day 1 switched to 60 mg/m[2] orally on the day 8. Follow-up visits with physical evaluation, chest CT and laboratory tests have been realized every 3 months for 2 years and then every 6 months. Tolerability, side effects, relative dose intensity and survival were evaluated.
Results:
Seventy four patients (pts) were recruited to the SWITCH I study: 53 men and 21 women, 45 smokers, 23 ex- smokers and 6 non-smokers. Median age was 64 y (48-75 y). Tumor was squamous in 46, adenocarcinoma in 22, giant cell in 4 and NOS in 2 pts. Stage of the tumor was IB in19, IIA in 8, IIB in 22 and IIIA in 25. Mean number of applied cycles was 3.77 four planned cycles finished 82,4% patients. The most frequent hematological toxicities grade 3/4 were neutropenia (25.7 %), leukopenia (16.2 %), anemia (8.1 %) and trombocytopenia (2.7 %). Non-hematological toxicities were alopecia (12.2 %), nausea (4.1%), nefrotoxicity (1.4%) and diarrhoea (1,4%). Median of follow up was 4.73 y. Median of disease specific survival was 7.63 y (95% CI: 4.57 to NR), median of overall survival (MOS) was 5.9 y (95% CI, 3.7 to, NR) and median of disease free survival (DFS) 4.43 y . Three-year survival of 70.3% and five-year survival of 56,2% were reached.
Conclusion:
Adjuvant chemotherapy with carboplatinum and vinorelbine given intravenously on the day 1 and orally on the day 8 in 21 day regimen appears to be a comfortable and tolerable therapy in radically resected NSCLC. It provides higher dose intensity and more of acomplished treatments compared to big adjuvant trials and LACE meta-analysis, in which these parametres varied between 50 % to 76 % only. Survival results are comparable to LACE (3-year survival 70,3% vs 64.3%), 5-year survival 56,2% vs 55.1%) and MOS 5.9 vs 5.15 y). Supported by Grant Grant IGA MZ ČR NT/13569 of the Czech Ministry of Health.
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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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P1.01-019 - Czech Experience with Crizotinib in the Personalized Treatment of NSCLC (ID 305)
09:30 - 09:30 | Author(s): V. Kolek
- 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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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- 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): V. Kolek
- 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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P3.08 - 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): V. Kolek
- 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
