KRAS gene mutation status and sensitivity to pemetrexed: A retrospective analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19154-e19154
Author(s):  
Manali K. Kamdar ◽  
Teresa Parent ◽  
Paul R. Walker
Keyword(s):  
Overall Survival ◽  
Maintenance Therapy ◽  
Lung Adenocarcinoma ◽  
Kras Mutation ◽  
Stage Iv ◽  
Stage Iiib ◽  
Smoking History ◽  
Kras Gene ◽  
Kras Mutations ◽  
Mutation Status

e19154 Background: KRAS is the most frequently mutated oncogene (25%) in lung adenocarcinoma. KRAS mutations are a negative prognostic factor for survival. Recent phase II trial with a MEK inhibitor has shown promising efficacy albeit at the cost of higher adverse events. Preclinical work by Moran et al showed that antifolate therapies like pemetrexed decrease KRAS gene expression in KRAS wild type and KRAS mutant but do not do so in KRAS mutant amplified cells. Targeted therapies for EGFR, ALK and ROS1 have increased the survival for lung adenocarcinoma expressing these actionable targets. No therapies are yet approved for KRAS mutant subsets. Hence therapeutic strategies that target this cohort represent an unmet medical need. Methods: We reviewed data from patients (pts) in our thoracic oncology clinic with stage IIIB and stage IV lung adenocarcinoma with KRAS mutation positive tumours who received pemetrexed either during induction or maintenance therapy. Pt characteristics including age, sex, race, smoking history, KRAS mutation subtype and overall survival were analyzed. Results: Between April 2010 and October 2012 we treated 154 pts with stage IIIB and stage IV lung adenocarcinoma. Of these 154 pts we found 34 patients with KRAS mutation positive tumours. 10 pts out of 34 pts with KRAS mutation positive tumours received pemetrexed during induction or maintenance therapy and were analyzed further. Median age 63. 60% females. 90% Caucasians. 90% were smokers. KRAS 12C mutation was found in 2 pts, KRAS 12V in 4, KRAS 12A in 3 and KRAS 13A in 1 pt. 4(40%) patients died. Median overall survival (OS) in the KRAS 12C, 12V, 12A and 13A was 14, 9.5, 10 and 12 months respectively. Conclusions: The median OS in published series is 15.4, 14, 8 and 7 months in the KRAS 12C, 12V, 12A and 13A cohorts respectively (Rosell et al). Our analysis found that pts with KRAS 12C, 12A and 13A mutation had a survival advantage with pemetrexed therapy as compared to pts with KRAS 12V mutation. Thus this retrospective study supports the concept that KRAS mutation status affects sensitivity to antifolate therapy (pemetrexed).

INVESTIGATION KRAS MUTATION IN CIRCULATION TUMOR DNA IN DIFFERENT STAGES OF COLORECTAL CANCER

2019 ◽  
Vol 65 (5) ◽  
pp. 701-707
Author(s):  
Vitaliy Shubin ◽  
Yuriy Shelygin ◽  
Sergey Achkasov ◽  
Yevgeniy Rybakov ◽  
Aleksey Ponomarenko ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Plasma Volume ◽  
Kras Mutation ◽  
Stage Iv ◽  
Circulating Tumor Dna ◽  
Stage Ii ◽  
Kras Gene ◽  
Kras Mutations ◽  
Droplet Pcr ◽  
Tumor Dna

To determine mutations in the plasma KRAS gene in patients with colorectal cancer was the aim of this study. The material was obtained from 44 patients with colorectal cancer of different stages (T1-4N0-2bM0-1c). Plasma for the presence of KRAS gene mutation in circulating tumor DNA was investigated using digital droplet polymerase chain reaction (PCR). KRAS mutations in circulating tumor DNA isolated from 1 ml of plasma were detected in 13 (30%) patients with cancer of different stages. Of these, with stage II, there were 3 patients, with III - 5 and with IV - 5. Patients who did not have mutations in 1 ml of plasma were analyzed for mutations of KRAS in circulating tumor DNA isolated from 3 ml of plasma. Five more patients with KRAS mutations were found with II and III stages. The highest concentrations of circulating tumor DNA with KRAS mutation were found in patients with stage IV. The increase in plasma volume to 3 ml did not lead to the identification of mutations in I stage. This study showed that digital droplet PCR allows identification of circulating tumor DNA with the KRAS mutations in patients with stage II-IV of colon cancer. The results can be used to determine the degree of aggressiveness of the tumor at different stages of the disease, but not the 1st, and it is recommended to use a plasma volume of at least 3 ml.

scholarly journals Ανίχνευση μεταλλάξεων του EGFR και KRAS σε ασθενείς με μη-μικροκυτταρικό καρκίνο του πνεύμονα και διερεύνηση της αξίας τους ως προβλεπτικών παραγόντων ανταπόκρισης στη θεραπεία

2013 ◽  
Author(s):  
Αριστέα Καλυκάκη
Keyword(s):  
Kras Mutation ◽  
Smoking History ◽  
Egfr Mutations ◽  
Front Line ◽  
Kras Mutations ◽  
Primary Tumors ◽  
Mutation Status ◽  
Kras Mutation Status ◽  
Line Chemotherapy ◽  
Exon 19

The purpose of this study was to investigate whether the EGFR and KRASmutation status are predictive factors for Greeks patients with NSCLC. Initially, wecalculated the rate and the pattern of EGFR and KRAS mutations in 639 patients withNSCLC and then we correlated the mutations status with clinicopathologicalcharacteristics, the response to 1st line chemotherapy and patients’ overall survival.We also investigated the association of EGFR mutations with the EGFR geneamplification. Finally, in a group of 25 patients the mutation status of these genes inthe primary tumors and the corresponding metastasis was evaluated.The genetic analysis performed in FFPE tissue samples of primary tumor ormetastasis. DNA was extracted using universal techniques. For mutation analysis exons18, 19, 20 and 21 of the EGFR and exon 2 of KRAS genes were sequentially amplified bypolymerase chain reaction (PCR) and subjected to direct sequencing. Finally, EGFRamplification was determined by quantitative real time PCR.Analysis of EGFR mutations was successful performed in 634 patients andmutations were detected in 100 (15.8%) of them. Activating mutations were detected in 8.4%. The most common mutations were deletions of 4-5 codons in exon 19 (del 19,71.7%, 38/53) and the missense mutation at position 858 (L858R) in exon 21 (22.6%,12/53). Also in 47 (7.4%) patients other mutations were detected in four exons ofEGFR, which have been reported previously or are new. We found that the incidenceof EGFR mutations was statistically significant in women with no smoking history andwith adenocarcinoma histology.The mutation analysis of the KRAS gene was successfully performed on 399patients and mutations detected in 20.8% of them (83/399). Especially, 92.8% of themutations were found at codon 12 and 7.2% at codon 13. KRAS mutations weresignificantly associated with smoking history with higher incidence in smokers thannonsmokers. There was also a significant association between KRAS mutations andadenocarcinoma histology.The predictive value of EGFR and KRAS mutations was examined in a subgroupof patients (n=162) with NSCLC who received chemotherapy as 1st line therapy.Patients with classical EGFR mutations had a higher probability of response (55.6%) to front-line chemotherapy as compared to those with wild type EGFR (21.8%) (p =0.023). Multivariate analysis revealed the 'classical' activating EGFR mutations as anindependent predictive factor for response to 1st line chemotherapy. There was nosignificant correlation between the EGFR or KRAS mutation status and the time totumor progression. The presence of activating EGFR but not of KRAS mutations wasassociated with a significantly higher overall survival compared to patients withoutmutations treated with platinum-based front-line chemotherapy.Epidermal growth factor receptor and KRAS mutation status was differentbetween primary tumors and corresponding metastases in 7 (28%) and 6 (24%) of the25 patients, respectively. This discrepancy was not statistically significant with theMcNemar’s test.EGFR amplification was found in 7.2% (6/83) of primary tumors. Among thepatients with EGFR gene amplification none carried KRAS mutations while 2 had EGFR exon 19 deletion.

scholarly journals Simplified Molecular Classification of Lung Adenocarcinomas Based on EGFR, KRAS, and TP53 Mutations

2019 ◽  
Author(s):  
Roberto Ruiz-Cordero ◽  
Junsheng Ma ◽  
Abha Khanna ◽  
Genevieve Ray Lyons ◽  
Waree Rinsurongkawong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Survival Data ◽  
Molecular Subtypes ◽  
Stage Iv ◽  
Molecular Classification ◽  
Smoking History ◽  
Egfr Mutations ◽  
Prognostic Features ◽  
Mutational Status

Abstract Introduction: Gene expression profiling has consistently identified three molecular subtypes of lung adenocarcinoma that have prognostic implications. To facilitate stratification of patients with this disease into similar molecular subtypes, we developed and validated a simple, mutually exclusive classification. Methods: Mutational status of EGFR, KRAS, and TP53 was used to define six mutually exclusive molecular subtypes. A development cohort of 283 cytology specimens of lung adenocarcinoma was used to evaluate the associations between the proposed classification and clinicopathologic variables including demographic characteristics, smoking history, fluorescence in situ hybridization and molecular results. For validation and prognostic assessment, 63 of the 283 cytology specimens with available survival data were combined with a separate cohort of 428 surgical pathology specimens of lung adenocarcinoma. Results: The proposed classification yielded significant associations between these molecular subtypes and clinical and prognostic features. We found better overall survival in patients who underwent surgery and had tumors enriched for EGFR mutations. Worse overall survival was associated with older age, stage IV disease, and tumors with co- mutations in KRAS and TP53. Interestingly, neither chemotherapy nor radiation therapy showed benefit to overall survival. Conclusions: The mutational status of EGFR, KRAS, and TP53 can be used to easily classify lung adenocarcinoma patients into six subtypes that show a relationship with prognosis, especially in patients who underwent surgery, and these subtypes are similar to classifications based on more complex genomic methods reported previously.

scholarly journals Simplified Molecular Classification of Lung Adenocarcinomas Based on EGFR, KRAS, and TP53 Mutations

2019 ◽  
Author(s):  
Roberto Ruiz-Cordero ◽  
Junsheng Ma ◽  
Abha Khanna ◽  
Genevieve Ray Lyons ◽  
Waree Rinsurongkawong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Survival Data ◽  
Molecular Subtypes ◽  
Stage Iv ◽  
Molecular Classification ◽  
Smoking History ◽  
Egfr Mutations ◽  
Prognostic Features ◽  
Mutational Status

Abstract Background: Gene expression profiling has consistently identified three molecular subtypes of lung adenocarcinoma that have prognostic implications. To facilitate stratification of patients with this disease into similar molecular subtypes, we developed and validated a simple, mutually exclusive classification. Methods: Mutational status of EGFR, KRAS, and TP53 was used to define seven mutually exclusive molecular subtypes. A development cohort of 283 cytology specimens of lung adenocarcinoma was used to evaluate the associations between the proposed classification and clinicopathologic variables including demographic characteristics, smoking history, fluorescence in situ hybridization and molecular results. For validation and prognostic assessment, 63 of the 283 cytology specimens with available survival data were combined with a separate cohort of 428 surgical pathology specimens of lung adenocarcinoma. Results: The proposed classification yielded significant associations between these molecular subtypes and clinical and prognostic features. We found better overall survival in patients who underwent surgery and had tumors enriched for EGFR mutations. Worse overall survival was associated with older age, stage IV disease, and tumors with co-mutations in KRAS and TP53. Interestingly, neither chemotherapy nor radiation therapy showed benefit to overall survival. Conclusions: The mutational status of EGFR, KRAS, and TP53 can be used to easily classify lung adenocarcinoma patients into seven subtypes that show a relationship with prognosis, especially in patients who underwent surgery, and these subtypes are similar to classifications based on more complex genomic methods reported previously.

The prognostic value of KRAS mutation subtypes and PD-L1 expression in patients with lung adenocarcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20022-e20022
Author(s):  
Luwei Tao ◽  
Jingxin Sun ◽  
Tarek Mekhail ◽  
Lingbin Meng ◽  
Cheng Fang ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Lung Adenocarcinoma ◽  
Kras Mutation ◽  
Prognostic Value ◽  
Clinical Stage ◽  
Stage Iv ◽  
Tumor Stage ◽  
Kras Mutations ◽  
Radio Therapy ◽  
Expression Status

e20022 Background: KRAS gene mutations are found in 20-30% of non-small cell lung cancer (NSCLC), especially in adenocarcinoma. Compared to EGFR and ALK mutations, KRAS mutation in NSCLC may be associated with poorer prognosis. However, prognostic value of different KRAS mutation subtypes in NSCLC remains unknown. The goal of this study is to evaluate the association of KRAS mutation subtypes, PD-L1 expression and clinical outcome in patients diagnosed with primary lung adenocarcinoma. Methods: A total of 256 patients diagnosed with KRAS mutated (determined by pyrosequencing) lung adenocarcinoma between 2011 and 2015 in AdventHealth-Orlando were evaluated for their cancer staging, Relapse-free survival (RFS) and overall survival (OS). PD-L1 staining was performed in a subgroup of 95 patients from the same cohort. PD-L1 expression was determined with immunohistochemistry staining using Ventana PD-L1 (SP263) assay. Results: In this cohort of patients, 65 had stage I disease, 29 stage II, 49 stage III, 110 stage IV and 3 with no clinical stage information; 104 male, 152 female; median age 67. All patients received standard surgical/chemo/radio therapy according to the disease stages. Only one single patient received immunotherapy. Nine subtypes of KRAS mutation were detected, predominantly in codon 12. Three major subtypes account for 83.6% KRAS mutations, namely G12C (45.7%), G12V (21.9%) and G12D (16.0%). We found that these three major subtypes had no difference in cancer stages (P = 0.58) or brain metastasis at diagnosis (P = 0.78). Kaplan Meier analysis also showed similar OS and RFS among all KRAS subtype. 34% of KRAS mutated patients were found to be PD-L1 positive with tumor proportion score of greater than or equal to 1. PD-L1 expression status was indistinct among the three major mutation subtypes (P = 0.38). Of interest, among patients with G12C mutation, positive PD-L1 expression was associated with significantly shorter OS (5.7 vs 12.8 months; P = 0.007). In contrast, for patients with other KRAS mutation subtypes, PD-L1 expression status had no impact on OS (P = 0.63). Conclusions: The clinical courses, including tumor stage at diagnosis, presence of brain metastasis, OS and RFS, are similar among lung adenocarcinoma patients with different KRAS mutation subtypes. Additionally, PD-L1 expression status appears to be independent of KRAS mutation subtypes. Of note, concurrent PD-L1 expression and G12C mutation is associated with particularly poorer prognosis. Further study is needed to see if PD1/PD-L1 block may improve outcome of this group of patients.

scholarly journals Simplified Molecular Classification of Lung Adenocarcinomas Based on EGFR, KRAS, and TP53 Mutations

2020 ◽  
Author(s):  
Roberto Ruiz-Cordero ◽  
Junsheng Ma ◽  
Abha Khanna ◽  
Genevieve Ray Lyons ◽  
Waree Rinsurongkawong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Survival Data ◽  
Molecular Subtypes ◽  
Stage Iv ◽  
Molecular Classification ◽  
Smoking History ◽  
Egfr Mutations ◽  
Prognostic Features ◽  
Mutational Status

Abstract Background: Gene expression profiling has consistently identified three molecular subtypes of lung adenocarcinoma that have prognostic implications. To facilitate stratification of patients with this disease into similar molecular subtypes, we developed and validated a simple, mutually exclusive classification. Methods: Mutational status of EGFR , KRAS , and TP53 was used to define seven mutually exclusive molecular subtypes. A development cohort of 283 cytology specimens of lung adenocarcinoma was used to evaluate the associations between the proposed classification and clinicopathologic variables including demographic characteristics, smoking history, fluorescence in situ hybridization and molecular results. For validation and prognostic assessment, 63 of the 283 cytology specimens with available survival data were combined with a separate cohort of 428 surgical pathology specimens of lung adenocarcinoma. Results: The proposed classification yielded significant associations between these molecular subtypes and clinical and prognostic features. We found better overall survival in patients who underwent surgery and had tumors enriched for EGFR mutations. Worse overall survival was associated with older age, stage IV disease, and tumors with co-mutations in KRAS and TP53 . Interestingly, neither chemotherapy nor radiation therapy showed benefit to overall survival. Conclusions: The mutational status of EGFR , KRAS , and TP53 can be used to easily classify lung adenocarcinoma patients into seven subtypes that show a relationship with prognosis, especially in patients who underwent surgery, and these subtypes are similar to classifications based on more complex genomic methods reported previously.

Impact of KRAS mutational status on clinical outcomes in patients receiving capecitabine based chemotherapy.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 436-436
Author(s):  
Nirit Yarom ◽  
Gillian Gresham ◽  
Nana Boame ◽  
Derek J. Jonker
Keyword(s):  
Clinical Outcomes ◽  
Kras Mutation ◽  
Hazard Ratio ◽  
Prognostic Impact ◽  
Kras Gene ◽  
Kras Mutations ◽  
Mutation Status ◽  
Mutational Status ◽  
Kras Mutation Status ◽  
Line Chemotherapy

436 Background: Mutations affecting the KRAS gene are established predictive markers of outcome with anti–epithelial growth factor receptor antibodies in metastatic colorectal cancer (mCRC). The relevance of these markers for chemotherapy has not been established. This analysis was performed to assess the predictive impact of KRAS mutation status in patients receiving chemotherapy. Methods: KRAS mutational status was available for 223 patients treated for mCRC. Predictive analysis of mutational status by type of fluoropyrmidine the 1st-line regimen contained (either capecitabine [C] based chemotherapy or infusional 5Fluorouracil [I-5Fu]) for clinical outcomes: progression-free survival (PFS), time to chemotherapy resistance (TTCR) and overall survival (OS). Results: KRAS mutations were observed in 43.5% of the patients. 165 patients received I-5Fu, 44 patients received C. KRAS mutation status (wild type [WT] v mutated [MT]) had no prognostic impact for OS (hazard ratio [HR], 0.81; CI, 0.69 to 1.1 p=0.17) for PFS (hazard ratio [HR], 0.87; CI, 0.66 to 1.14 p=0.3) and TTCR (hazard ratio [HR], 0.85; CI, 0.65to 1.12 p=0.26). C based 1st-line chemotherapy vs. I- 5FU based was predictive of PFS (hazard ratio [HR], 0.52; CI, 0.37 to 0.74 p=0.0003) and TTCR (hazard ratio [HR], 0.54; CI, 0.38 to 0.75p=0.0005) and not of OS (hazard ratio [HR], 0.74; CI, 0.52 to 1.1 p=0.1). KRAS mutational status had predictive impact in patients receiving C based 1st-line chemotherapy on OS (hazard ratio [HR], 0.47; CI, 0.23 to 0.948 p<0.0001) TTCR (hazard ratio [HR], 0.49; CI, 0.25 to 0.97 p=0.0398) and was not predictive of PFS (hazard ratio [HR], 0.78; CI, 0.4 to 1.53 p=0.47) Conclusions: KRAS gene mutation status was predicitve for OS and for TTCR in patients who received C based 1st-line chemotherapy.

scholarly journals Simplified Molecular Classification of Lung Adenocarcinomas Based on EGFR, KRAS, and TP53 Mutations

2020 ◽  
Author(s):  
Roberto Ruiz-Cordero ◽  
Junsheng Ma ◽  
Abha Khanna ◽  
Genevieve Ray Lyons ◽  
Waree Rinsurongkawong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Survival Data ◽  
Molecular Subtypes ◽  
Stage Iv ◽  
Molecular Classification ◽  
Smoking History ◽  
Egfr Mutations ◽  
Prognostic Features ◽  
Mutational Status

Abstract Background: Gene expression profiling has consistently identified three molecular subtypes of lung adenocarcinoma that have prognostic implications. To facilitate stratification of patients with this disease into similar molecular subtypes, we developed and validated a simple, mutually exclusive classification. Methods: Mutational status of EGFR , KRAS , and TP53 was used to define seven mutually exclusive molecular subtypes. A development cohort of 283 cytology specimens of lung adenocarcinoma was used to evaluate the associations between the proposed classification and clinicopathologic variables including demographic characteristics, smoking history, fluorescence in situ hybridization and molecular results. For validation and prognostic assessment, 63 of the 283 cytology specimens with available survival data were combined with a separate cohort of 428 surgical pathology specimens of lung adenocarcinoma. Results: The proposed classification yielded significant associations between these molecular subtypes and clinical and prognostic features. We found better overall survival in patients who underwent surgery and had tumors enriched for EGFR mutations. Worse overall survival was associated with older age, stage IV disease, and tumors with co-mutations in KRAS and TP53 . Interestingly, neither chemotherapy nor radiation therapy showed benefit to overall survival. Conclusions: The mutational status of EGFR , KRAS , and TP53 can be used to easily classify lung adenocarcinoma patients into seven subtypes that show a relationship with prognosis, especially in patients who underwent surgery, and these subtypes are similar to classifications based on more complex genomic methods reported previously.

scholarly journals Simplified Molecular Classification of Lung Adenocarcinomas Based on EGFR, KRAS, and TP53 Mutations

2019 ◽  
Author(s):  
Roberto Ruiz-Cordero ◽  
Junsheng Ma ◽  
Abha Khanna ◽  
Genevieve Lyons ◽  
Waree Rinsurongkawong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Survival Data ◽  
Molecular Subtypes ◽  
Stage Iv ◽  
Molecular Classification ◽  
Smoking History ◽  
Prognostic Features ◽  
Prognostic Assessment ◽  
Mutational Status

AbstractIntroductionGene expression profiling has consistently identified three molecular subtypes of lung adenocarcinoma that have prognostic implications. To facilitate stratification of patients with this disease into similar molecular subtypes, we developed and validated a simple, mutually exclusive classification.MethodsMutational status of EGFR, KRAS, and TP53 was used to define six mutually exclusive molecular subtypes. A development cohort of 283 cytology specimens of lung adenocarcinoma was used to evaluate the associations between the proposed classification and clinicopathologic variables including demographic characteristics, smoking history, fluorescence in situ hybridization and molecular results. For validation and prognostic assessment, 63 of the 283 cytology specimens with available survival data were combined with a separate cohort of 428 surgical pathology specimens of lung adenocarcinoma.ResultsThe proposed classification yielded significant associations between these molecular subtypes and clinical and prognostic features. We found better overall survival in patients who underwent surgery and had tumors enriched for EGFR mutations. Worse overall survival was associated with older age, stage IV disease, and tumors with comutations in KRAS and TP53. Interestingly, neither chemotherapy nor radiation therapy showed benefit to overall survival.ConclusionsThe mutational status of EGFR, KRAS, and TP53 can be used to easily classify lung adenocarcinoma patients into six subtypes that show a relationship with prognosis, especially in patients who underwent surgery, and these subtypes are similar to classifications based on more complex genomic methods reported previously.

scholarly journals Experience of pemetrexed in maintenance therapy for metastatic lung adenocarcinoma

2021 ◽  
Vol 2 (1) ◽  
pp. 35-42
Author(s):  
L. Yu. Vladimirova ◽  
A. E. Storozhakova ◽  
E. A. Kalabanova ◽  
P. N. Meshcheryakov ◽  
S. V. Oskin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Maintenance Therapy ◽  
Lung Adenocarcinoma ◽  
Clinical Case ◽  
Lower Lobe ◽  
Stage Iv ◽  
Driver Mutations ◽  
Advanced Lung Cancer ◽  
Second Line

Lung cancer is among the most common malignant diseases in Russia. In 80–90%, its morphological type is nonsmall cell lung cancer. Stage IV primary advanced lung cancer is diagnosed in 41% of patients. Median overall survival in stage IV patients receiving chemotherapy is 7–12 months. Treatment for stage IV lung adenocarcinoma is based on predictive and prognostic factors. Chemotherapy, chemoimmunotherapy or immunotherapy is recommended in the absence of driver mutations in the EGFR (exons 19 and 21) and BRAF genes, ALK and ROS1 translocations.Platinum- based regimens are preferred as the fi rst-line chemotherapy. Stabilization, partial or complete response after 4–6 chemotherapy cycles allow for maintenance therapy with pemetrexed to increase progression-free survival and overall survival.Purpose of the study. Using a real clinical case, to confirm the efficacy of pemetrexed in the treatment for stage IV lung adenocarcinoma in the second-line therapy in combination with platinum- based agents and in a maintenance therapy.A clinical case of a patient with central cancer of the lower lobe of the right lung St IV (cT3N2M1) is presented; the first treatment stage involved 3 cycles of the fi rst-line polychemotherapy (paclitaxel 175 mg/m² intravenously on day 1, carboplatin AUC 5 intravenously on day 1, every 3 weeks), and 6 cycles of the second-line polychemotherapy (pemetrexed 500 mg/m2 intravenously on day 1, cisplatin 75 mg/m² intravenously on day 1 of the 21-day cycle). Stabilization of the disease was achieves, and 20 cycles of maintenance therapy with pemetrexed followed; the achieved effect persisted and was confirmed by spiral X-ray computed tomography every 3 months. The objective effect of anticancer therapy was assessed according to the RECIST 1.1 criteria. It took 20 months from the beginning of the second-line anticancer medical therapy to progression, and 16 months from the start of maintenance pemetrexed to progression. The safety profile was satisfactory, and the ECOG performance status 0 maintained. Only one adverse effect, degree I general weakness, was noted, which did not have a negative impact on the patient's quality of life.

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