This letter provides a review of the report by Peng et al on a unique case of non-small cell lung cancer(NSCLC),specifically lung adenocarcinoma,featuring reactive oxygen species proto-oncogene 1-receptor(ROS1)co-muta...This letter provides a review of the report by Peng et al on a unique case of non-small cell lung cancer(NSCLC),specifically lung adenocarcinoma,featuring reactive oxygen species proto-oncogene 1-receptor(ROS1)co-mutation.The case involves a 64-year-old patient who exhibited both epidermal growth factor receptor(EGFR)L858R mutation and ROS1 rearrangement,achieving significant disease stabilization following treatment with crizotinib.This rare EGFR/ROS1 co-mutation poses distinct challenges for clinical management and highlights the necessity of personalized treatment strategies.While third-generation EGFR tyrosine kinase inhibitors(TKIs),such as osimertinib,are commonly regarded as first-line therapies,recent studies indicate that crizotinib may offer superior disease control in certain EGFR-mutant patients,particularly those who exhibit poor responses to EGFR TKIs.The case also examines the influence of tumor cell genetic heterogeneity on treatment response,underscoring the importance of evaluating tumor characteristics.In patients with EGFR/ROS1 co-mutation,gefitinib is generally effective as a first-line treatment;however,its efficacy can be limited,whereas crizotinib has demonstrated improved disease control.Future research should focus on identifying optimal treatment strategies for patients with EGFR/ROS1 co-mutation to enhance patient outcomes.In conclusion,this case report not only illustrates the effectiveness of crizotinib in managing patients with EGFR/ROS1 co-mutation but also underscores the importance of personalized treatment approaches,offering valuable insights for improving clinical outcomes in NSCLC patients with complex genetic profiles.TO THE EDITOR I read with great interest the case report by Peng et al[1],titled“Concomitant Epidermal Growth Factor Receptor Mutation/C-ROS Oncogene 1 Rearrangement in Non-Small Cell Lung Cancer”,published in the World Journal of Clinical Oncology[1].This report presents a compelling case of the exceedingly rare epidermal growth factor receptor(EGFR)/reactive oxygen species proto-oncogene 1-receptor(ROS1)co-mutation in non-small cell lung cancer(NSCLC),specifically in a patient with lung adenocarcinoma.The authors describe a 64-year-old woman with an EGFR L858R mutation and ROS1 rearrangement,who achieved notable disease stability with prolonged crizotinib treatment.This case,with its distinct clinical features and challenges inherent to EGFR/ROS1 co-mutations,provides valuable insights for the oncology community and underscores the potential efficacy of ROS1-targeted therapies in treating co-mutated NSCLC.展开更多
Objective: Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC). Despite its initial efficacy, patients ultimately acquire resista...Objective: Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC). Despite its initial efficacy, patients ultimately acquire resistance to crizotinib within 1 year. In such patients, the optimal sequential therapy after crizotinib treatment remains unknown. This study explored which sequential therapy option confers the greatest benefit.Methods: A total of 138 patients with advanced ALK-positive NSCLC resistant to crizotinib were studied. Based on patterns of disease progression of metastases, patients were divided into 3 groups: brain progression, non-liver progression, and liver progression. Sequential therapies included crizotinib continuation plus local therapy, nextgeneration ALK inhibitors(ALKi's), and chemotherapy. The primary endpoint was overall survival(OS) from the time of crizotinib resistance to death or last follow-up.Results: The 138 patients included 64 cases with progression in brain, 57 cases in non-liver sites and 17 cases in liver. A significant difference in OS was observed among the distinct progression pattern(median OS, 25.4 months in brain, 15.8 months in non-liver, and 10.8 months in liver, respectively, P=0.020). The difference in OS among sequential therapies was statistically significant in the non-liver progression group(median OS, 27.6 months with next-generation ALKi's, 13.3 months with crizotinib continuation, and 10.8 months with chemotherapy,respectively, P=0.019). However, crizotinib continuation plus local therapy seems to provide non-inferior median OS compared with next-generation ALKi's for patients with brain progression(median OS, 28.9 months vs.32.8 months, P=0.204). And no significant differences in OS were found in patients with progression in liver(P=0.061).Conclusions: Crizotinib continuation together with local therapy might be a feasible strategy for patients with progression in brain beyond crizotinib resistance, as well as next-generation ALKi's. Next-generation ALKi's tended to provide a survival benefit in patients with non-liver progression.展开更多
Objective: Crizotinib has demonstrated promising efficacy in patients with anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC) in clinical trials. We conducted this retrospective multicenter stu...Objective: Crizotinib has demonstrated promising efficacy in patients with anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC) in clinical trials. We conducted this retrospective multicenter study to assess the outcomes of crizotinib therapy in, to our knowledge, a large sample cohort of patients with ALKpositive advanced NSCLC.Methods: We reviewed the medical records of 484 unselected ALK-positive NSCLC patients treated with crizotinib at 5 cancer centers in China from January 2013 to November 2017. Clinical data were collected from the initiation of crizotinib therapy to Response Evaluation Criteria in Solid Tumors(RECIST)-defined progressive disease(PD).Results: A total of 428 eligible ALK-positive NSCLC patients were enrolled, 273(63.8%) of whom received crizotinib as first-line treatment. The median progression-free survival(PFS) and overall survival(OS) from the initiation of crizotinib treatment were 14.4 [95% confidence interval(95% CI), 12.4-16.4] months and 53.4(95%CI, 33.7-73.1) months, respectively. In subgroup analyses, patients who received crizotinib as first-line treatment showed a higher disease control rate(DCR) and a longer median OS compared with second-/later-line crizotinib treatment(94.8% and OS not reached vs. 89.0% and 40.5 months, respectively). For 261 patients with RECISTdefined PD, multivariate Cox analysis revealed that in patients who received first-line crizotinib therapy, continued crizotinib beyond progressive disease(CBPD) and next-generation ALK inhibitors after crizotinib failure were associated with improved survival.Conclusions: This study has demonstrated the clinically meaningful benefit of crizotinib treatment in a large cohort of Chinese ALK-positive NSCLC patients. CBPD and next-generation ALK inhibitor treatment may provide improved survival after RECIST-defined progression on crizotinib.展开更多
Crizotinib,a small molecular tyrosine kinase inhibitor,manifests dramatic responses in patients with non-small cell lung cancer with echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase(EML4-ALK...Crizotinib,a small molecular tyrosine kinase inhibitor,manifests dramatic responses in patients with non-small cell lung cancer with echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase(EML4-ALK)rearrangements.ALK gene point mutation is the primary mechanism of acquired crizotinib resistance;however,the intrinsic mechanism is not fully understood.Here,we report a patient with a low mutant allele fraction(MAF)of EML4-ALK rearrangement,who experienced primary resistance to crizotinib treatment.The patient was a 66-year-old Chinese man,who had a history of metastatic lung cancer and was treated with first-and third-generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR TKIs).After 14 months of osimertinib treatment,his disease progressed,and next-generation sequencing was performed from a liquid biopsy of the patient’s blood.An EML4-ALK rearrangement was found and crizotinib was administered.The patient’s lung lesions continued to progress after one month of crizotinib treatment,and pemetrexed-bevacizumab was initiated.After two cycles of chemotherapy,the metastatic cancers shrunk,and the patient maintained stable disease at his last follow-up.EML4-ALK rearrangements can happen in patients with EGFR-positive NSCLC,after acquired resistance to EGFR TKI treatment.The EGFR T790M and C797G mutations occur in cis is a critical mechanism of resistance to osimertinib therapy.The MAF of EML4-ALK rearrangements in cancer cells might be a predictive factor for crizotinib treatment.展开更多
AIM To investigate the potential benefit of combining the cMET inhibitor crizotinib and cisplatin we performed in vitro combination studies.METHODS We tested three different treatment schemes in four non-small cell lu...AIM To investigate the potential benefit of combining the cMET inhibitor crizotinib and cisplatin we performed in vitro combination studies.METHODS We tested three different treatment schemes in four non-small cell lung cancer(NSCLC) cell lines with a different cMET/epidermal growth factor receptor genetic background by means of the sulforhodamine B assay and performed analysis with Calcusyn.RESULTS All treatment schemes showed an antagonistic effect in all cell lines,independent of the cMET status.Despite their different genetic backgrounds,all cell lines(EBC-1,HCC827,H1975 and LUDLU-1) showed antagonistic combination indexes ranging from 1.3-2.7.These results were independent of the treatment schedule.CONCLUSION These results discourage further efforts to combine cMET inhibition with cisplatin chemotherapy in NSCLC.展开更多
Objective： The relationship between anaplastic lymphoma kinase（ALK） expression in malignant pleural effusion（MPE） samples detected only by Ventana immunohistochemistry（IHC） ALK（D5F3） and the efficacy of ALKty...Objective： The relationship between anaplastic lymphoma kinase（ALK） expression in malignant pleural effusion（MPE） samples detected only by Ventana immunohistochemistry（IHC） ALK（D5F3） and the efficacy of ALKtyrosine kinase inhibitor therapy is uncertain.Methods： Ventana anti-ALK（D5F3） rabbit monoclonal primary antibody testing was performed on 313 cell blocks of MPE samples from Chinese patients with advanced lung adenocarcinoma, and fluorescence in situ hybridization（FISH） was used to verify the ALK gene status in Ventana IHC ALK（D5F3）-positive samples. The follow-up clinical data on patients who received crizotinib treatment were recorded.Results： Of the 313 MPE samples, 27（8.6%） were confirmed as ALK expression-positive, and the Ventana IHC ALK（D5F3）-positive rate was 17.3%（27/156） in wild-type epidermal growth factor receptor（EGFR） MPE samples. Twenty-three of the 27 IHC ALK（D5F3）-positive samples were positive by FISH. Of the 11 Ventana IHC ALK（D5F3）-positive patients who received crizotinib therapy, 2 patients had complete response（CR）, 5 had partial response（PR） and 3 had stable disease（SD）.Conclusions： The ALK gene expression status detected by the Ventana IHC ALK（D5F3） platform in MPE samples may predict tumor responsiveness to crizotinib in Chinese patients with advanced lung adenocarcinoma.展开更多
BACKGROUND Crizotinib-induce hepatotoxicity is rare and non-specific, and severe hepatotoxicity can develop into fatal liver failure. Herein, we report a case of fatal crizotinib-induced liver failure in a 37-year-old...BACKGROUND Crizotinib-induce hepatotoxicity is rare and non-specific, and severe hepatotoxicity can develop into fatal liver failure. Herein, we report a case of fatal crizotinib-induced liver failure in a 37-year-old Asian patient.CASE SUMMARY The patient complained of dyspnea and upper abdominal pain for a week in August 2017. He was diagnosed with anaplastic lymphoma kinase-rearranged lung adenocarcinoma combined with multiple distant metastases. Crizotinib was initiated as a first-line treatment at a dosage of 250 mg twice daily. No adverse effects were seen until day 46. On day 55, he was admitted to the hospital with elevated liver enzymes aspartate aminotransferase(AST)(402 IU/L), alanine aminotransferase(ALT)(215 IU/L) and total bilirubin(145 μmol/L) and was diagnosed with crizotinib-induced fulminant liver failure. Despite crizotinib discontinuation and intensive supportive therapy, the level of AST(1075 IU/L),ALT(240 IU/L) and total bilirubin(233 μmol/L) continued to rapidly increase,and he died on day 60.CONCLUSION Physicians should be aware of the potential fatal adverse effects of crizotinib.展开更多
BACKGROUND Due to the rarity of mesenchymal-epithelial transition factor(MET)fusions,the clinical efficacy of crizotinib has only been described in a few patients with MET fusions involving various fusion partners.Her...BACKGROUND Due to the rarity of mesenchymal-epithelial transition factor(MET)fusions,the clinical efficacy of crizotinib has only been described in a few patients with MET fusions involving various fusion partners.Herein,we report the clinical response to crizotinib of a patient with advanced poorly differentiated non-small cell carcinoma(NSCLC)having concurrent MET fusions.CASE SUMMARY A 46-year-old woman was diagnosed with poorly differentiated NSCLC(T4 N3 M1).With no classic driver mutations,she was treated with two cycles of gemcitabine and cisplatin without clinical benefit.Targeted sequencing revealed the detection of two concurrent MET fusions,KIF5 B-MET and novel MET-CDR2.Crizotinib was initiated at a dose of 250 mg twice daily.Within 4 wk of crizotinib therapy,repeat computed chromatography revealed a dramatic reduction in primary and metastatic lesions,assessed as partial response.She continued to benefit from crizotinib for 3 mo until disease progression and died within 1 mo despite receiving nivolumab therapy.CONCLUSION Crizotinib sensitivity was observed in an advanced poorly differentiated NSCLC patient with concurrent MET fusions KIF5 B-MET and MET-CDR2.Crizotinib can serve as a therapeutic option for patients with MET fusions.In addition,our case also highlights the importance of comprehensive genomic profiling particularly in patients with no classic driver mutation for guiding alternative therapeutic decisions.展开更多
Chemotherapy and targeted therapy remain the cornerstone of treatment of locally advanced and metastatic non-small cells lung cancer (NSCLC). Given the intrinsic chemoresistance of tumor cells, new treatment options h...Chemotherapy and targeted therapy remain the cornerstone of treatment of locally advanced and metastatic non-small cells lung cancer (NSCLC). Given the intrinsic chemoresistance of tumor cells, new treatment options have been developped. The knowledge of the molecular mechanisms of tumor biology, and signal transduction pathways activating cancer cells led to the identification of a new targeted therapy such as Crizotinib. The small molecule Crizotinib is a selective inhibitor of the receptor tyrosine kinase ALK (anaplastic lymphoma kinase) and its oncogenic variants (ALK fusion gene and some mutations of ALK). Phases I and II trials showed the efficacy of Crizotinib in the treatment of locally advanced and metastatic NSCLC expressing ALK. Thereafter, randomized Phase III trial confirmed the significant superiority of Crizotinib versus standard chemotherapy in terms of progression free survival and objective response with good tolerance;therefore, it has been approved by the Food and Drug Administration (FDA) as the standard treatment for locally advanced and metastatic ALK-positive NSCLC.展开更多
Background: Crizotinib is a tyrosine kinase inhibitor of ALK, MET and ROS1. In a safety database trial, it was suggested an association of Crizotinib with the development of renal cyst in patients with non-small-cell ...Background: Crizotinib is a tyrosine kinase inhibitor of ALK, MET and ROS1. In a safety database trial, it was suggested an association of Crizotinib with the development of renal cyst in patients with non-small-cell lung cancer (NSCLC). Aim: To report an uncommon side effect of Crizotinib in a patient with NSLC. Case Presentation: We report the case of a 68-year-old woman with NSCLC who developed bilateral progressive aseptic renal abscesses during Crizotinib treatment. Conclusion: Further studies may be necessary to determinate the risk of renal cyst development and the management of these complications.展开更多
INTRODUCTION Non-small cell lung cancer（NSCLC）is a common malignant disease with an extremely poor prognosis.Lung cancer has been reported to metastasize to the eye in 0.2%to7%of patients based on clinical studies,a...INTRODUCTION Non-small cell lung cancer（NSCLC）is a common malignant disease with an extremely poor prognosis.Lung cancer has been reported to metastasize to the eye in 0.2%to7%of patients based on clinical studies,and in 6%to 7%of patients based on postmortem histopathologic studies.展开更多
文摘This letter provides a review of the report by Peng et al on a unique case of non-small cell lung cancer(NSCLC),specifically lung adenocarcinoma,featuring reactive oxygen species proto-oncogene 1-receptor(ROS1)co-mutation.The case involves a 64-year-old patient who exhibited both epidermal growth factor receptor(EGFR)L858R mutation and ROS1 rearrangement,achieving significant disease stabilization following treatment with crizotinib.This rare EGFR/ROS1 co-mutation poses distinct challenges for clinical management and highlights the necessity of personalized treatment strategies.While third-generation EGFR tyrosine kinase inhibitors(TKIs),such as osimertinib,are commonly regarded as first-line therapies,recent studies indicate that crizotinib may offer superior disease control in certain EGFR-mutant patients,particularly those who exhibit poor responses to EGFR TKIs.The case also examines the influence of tumor cell genetic heterogeneity on treatment response,underscoring the importance of evaluating tumor characteristics.In patients with EGFR/ROS1 co-mutation,gefitinib is generally effective as a first-line treatment;however,its efficacy can be limited,whereas crizotinib has demonstrated improved disease control.Future research should focus on identifying optimal treatment strategies for patients with EGFR/ROS1 co-mutation to enhance patient outcomes.In conclusion,this case report not only illustrates the effectiveness of crizotinib in managing patients with EGFR/ROS1 co-mutation but also underscores the importance of personalized treatment approaches,offering valuable insights for improving clinical outcomes in NSCLC patients with complex genetic profiles.TO THE EDITOR I read with great interest the case report by Peng et al[1],titled“Concomitant Epidermal Growth Factor Receptor Mutation/C-ROS Oncogene 1 Rearrangement in Non-Small Cell Lung Cancer”,published in the World Journal of Clinical Oncology[1].This report presents a compelling case of the exceedingly rare epidermal growth factor receptor(EGFR)/reactive oxygen species proto-oncogene 1-receptor(ROS1)co-mutation in non-small cell lung cancer(NSCLC),specifically in a patient with lung adenocarcinoma.The authors describe a 64-year-old woman with an EGFR L858R mutation and ROS1 rearrangement,who achieved notable disease stability with prolonged crizotinib treatment.This case,with its distinct clinical features and challenges inherent to EGFR/ROS1 co-mutations,provides valuable insights for the oncology community and underscores the potential efficacy of ROS1-targeted therapies in treating co-mutated NSCLC.
文摘Objective: Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC). Despite its initial efficacy, patients ultimately acquire resistance to crizotinib within 1 year. In such patients, the optimal sequential therapy after crizotinib treatment remains unknown. This study explored which sequential therapy option confers the greatest benefit.Methods: A total of 138 patients with advanced ALK-positive NSCLC resistant to crizotinib were studied. Based on patterns of disease progression of metastases, patients were divided into 3 groups: brain progression, non-liver progression, and liver progression. Sequential therapies included crizotinib continuation plus local therapy, nextgeneration ALK inhibitors(ALKi's), and chemotherapy. The primary endpoint was overall survival(OS) from the time of crizotinib resistance to death or last follow-up.Results: The 138 patients included 64 cases with progression in brain, 57 cases in non-liver sites and 17 cases in liver. A significant difference in OS was observed among the distinct progression pattern(median OS, 25.4 months in brain, 15.8 months in non-liver, and 10.8 months in liver, respectively, P=0.020). The difference in OS among sequential therapies was statistically significant in the non-liver progression group(median OS, 27.6 months with next-generation ALKi's, 13.3 months with crizotinib continuation, and 10.8 months with chemotherapy,respectively, P=0.019). However, crizotinib continuation plus local therapy seems to provide non-inferior median OS compared with next-generation ALKi's for patients with brain progression(median OS, 28.9 months vs.32.8 months, P=0.204). And no significant differences in OS were found in patients with progression in liver(P=0.061).Conclusions: Crizotinib continuation together with local therapy might be a feasible strategy for patients with progression in brain beyond crizotinib resistance, as well as next-generation ALKi's. Next-generation ALKi's tended to provide a survival benefit in patients with non-liver progression.
文摘Objective: Crizotinib has demonstrated promising efficacy in patients with anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC) in clinical trials. We conducted this retrospective multicenter study to assess the outcomes of crizotinib therapy in, to our knowledge, a large sample cohort of patients with ALKpositive advanced NSCLC.Methods: We reviewed the medical records of 484 unselected ALK-positive NSCLC patients treated with crizotinib at 5 cancer centers in China from January 2013 to November 2017. Clinical data were collected from the initiation of crizotinib therapy to Response Evaluation Criteria in Solid Tumors(RECIST)-defined progressive disease(PD).Results: A total of 428 eligible ALK-positive NSCLC patients were enrolled, 273(63.8%) of whom received crizotinib as first-line treatment. The median progression-free survival(PFS) and overall survival(OS) from the initiation of crizotinib treatment were 14.4 [95% confidence interval(95% CI), 12.4-16.4] months and 53.4(95%CI, 33.7-73.1) months, respectively. In subgroup analyses, patients who received crizotinib as first-line treatment showed a higher disease control rate(DCR) and a longer median OS compared with second-/later-line crizotinib treatment(94.8% and OS not reached vs. 89.0% and 40.5 months, respectively). For 261 patients with RECISTdefined PD, multivariate Cox analysis revealed that in patients who received first-line crizotinib therapy, continued crizotinib beyond progressive disease(CBPD) and next-generation ALK inhibitors after crizotinib failure were associated with improved survival.Conclusions: This study has demonstrated the clinically meaningful benefit of crizotinib treatment in a large cohort of Chinese ALK-positive NSCLC patients. CBPD and next-generation ALK inhibitor treatment may provide improved survival after RECIST-defined progression on crizotinib.
文摘Crizotinib,a small molecular tyrosine kinase inhibitor,manifests dramatic responses in patients with non-small cell lung cancer with echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase(EML4-ALK)rearrangements.ALK gene point mutation is the primary mechanism of acquired crizotinib resistance;however,the intrinsic mechanism is not fully understood.Here,we report a patient with a low mutant allele fraction(MAF)of EML4-ALK rearrangement,who experienced primary resistance to crizotinib treatment.The patient was a 66-year-old Chinese man,who had a history of metastatic lung cancer and was treated with first-and third-generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR TKIs).After 14 months of osimertinib treatment,his disease progressed,and next-generation sequencing was performed from a liquid biopsy of the patient’s blood.An EML4-ALK rearrangement was found and crizotinib was administered.The patient’s lung lesions continued to progress after one month of crizotinib treatment,and pemetrexed-bevacizumab was initiated.After two cycles of chemotherapy,the metastatic cancers shrunk,and the patient maintained stable disease at his last follow-up.EML4-ALK rearrangements can happen in patients with EGFR-positive NSCLC,after acquired resistance to EGFR TKI treatment.The EGFR T790M and C797G mutations occur in cis is a critical mechanism of resistance to osimertinib therapy.The MAF of EML4-ALK rearrangements in cancer cells might be a predictive factor for crizotinib treatment.
基金Supported by Institute for Innovation,Science and Technology Flanders(IWT),NO:121114
文摘AIM To investigate the potential benefit of combining the cMET inhibitor crizotinib and cisplatin we performed in vitro combination studies.METHODS We tested three different treatment schemes in four non-small cell lung cancer(NSCLC) cell lines with a different cMET/epidermal growth factor receptor genetic background by means of the sulforhodamine B assay and performed analysis with Calcusyn.RESULTS All treatment schemes showed an antagonistic effect in all cell lines,independent of the cMET status.Despite their different genetic backgrounds,all cell lines(EBC-1,HCC827,H1975 and LUDLU-1) showed antagonistic combination indexes ranging from 1.3-2.7.These results were independent of the treatment schedule.CONCLUSION These results discourage further efforts to combine cMET inhibition with cisplatin chemotherapy in NSCLC.
基金supported by grants from the Beijing Municipal Science and Technology Commission(D141100000214003)the Natural Science Foundation of China(No.81641114)
文摘Objective： The relationship between anaplastic lymphoma kinase（ALK） expression in malignant pleural effusion（MPE） samples detected only by Ventana immunohistochemistry（IHC） ALK（D5F3） and the efficacy of ALKtyrosine kinase inhibitor therapy is uncertain.Methods： Ventana anti-ALK（D5F3） rabbit monoclonal primary antibody testing was performed on 313 cell blocks of MPE samples from Chinese patients with advanced lung adenocarcinoma, and fluorescence in situ hybridization（FISH） was used to verify the ALK gene status in Ventana IHC ALK（D5F3）-positive samples. The follow-up clinical data on patients who received crizotinib treatment were recorded.Results： Of the 313 MPE samples, 27（8.6%） were confirmed as ALK expression-positive, and the Ventana IHC ALK（D5F3）-positive rate was 17.3%（27/156） in wild-type epidermal growth factor receptor（EGFR） MPE samples. Twenty-three of the 27 IHC ALK（D5F3）-positive samples were positive by FISH. Of the 11 Ventana IHC ALK（D5F3）-positive patients who received crizotinib therapy, 2 patients had complete response（CR）, 5 had partial response（PR） and 3 had stable disease（SD）.Conclusions： The ALK gene expression status detected by the Ventana IHC ALK（D5F3） platform in MPE samples may predict tumor responsiveness to crizotinib in Chinese patients with advanced lung adenocarcinoma.
文摘BACKGROUND Crizotinib-induce hepatotoxicity is rare and non-specific, and severe hepatotoxicity can develop into fatal liver failure. Herein, we report a case of fatal crizotinib-induced liver failure in a 37-year-old Asian patient.CASE SUMMARY The patient complained of dyspnea and upper abdominal pain for a week in August 2017. He was diagnosed with anaplastic lymphoma kinase-rearranged lung adenocarcinoma combined with multiple distant metastases. Crizotinib was initiated as a first-line treatment at a dosage of 250 mg twice daily. No adverse effects were seen until day 46. On day 55, he was admitted to the hospital with elevated liver enzymes aspartate aminotransferase(AST)(402 IU/L), alanine aminotransferase(ALT)(215 IU/L) and total bilirubin(145 μmol/L) and was diagnosed with crizotinib-induced fulminant liver failure. Despite crizotinib discontinuation and intensive supportive therapy, the level of AST(1075 IU/L),ALT(240 IU/L) and total bilirubin(233 μmol/L) continued to rapidly increase,and he died on day 60.CONCLUSION Physicians should be aware of the potential fatal adverse effects of crizotinib.
基金Supported by the National Key R&D Program of ChinaNo. 2017YFC0907900 and 2017YFC0907904
文摘BACKGROUND Due to the rarity of mesenchymal-epithelial transition factor(MET)fusions,the clinical efficacy of crizotinib has only been described in a few patients with MET fusions involving various fusion partners.Herein,we report the clinical response to crizotinib of a patient with advanced poorly differentiated non-small cell carcinoma(NSCLC)having concurrent MET fusions.CASE SUMMARY A 46-year-old woman was diagnosed with poorly differentiated NSCLC(T4 N3 M1).With no classic driver mutations,she was treated with two cycles of gemcitabine and cisplatin without clinical benefit.Targeted sequencing revealed the detection of two concurrent MET fusions,KIF5 B-MET and novel MET-CDR2.Crizotinib was initiated at a dose of 250 mg twice daily.Within 4 wk of crizotinib therapy,repeat computed chromatography revealed a dramatic reduction in primary and metastatic lesions,assessed as partial response.She continued to benefit from crizotinib for 3 mo until disease progression and died within 1 mo despite receiving nivolumab therapy.CONCLUSION Crizotinib sensitivity was observed in an advanced poorly differentiated NSCLC patient with concurrent MET fusions KIF5 B-MET and MET-CDR2.Crizotinib can serve as a therapeutic option for patients with MET fusions.In addition,our case also highlights the importance of comprehensive genomic profiling particularly in patients with no classic driver mutation for guiding alternative therapeutic decisions.
文摘Chemotherapy and targeted therapy remain the cornerstone of treatment of locally advanced and metastatic non-small cells lung cancer (NSCLC). Given the intrinsic chemoresistance of tumor cells, new treatment options have been developped. The knowledge of the molecular mechanisms of tumor biology, and signal transduction pathways activating cancer cells led to the identification of a new targeted therapy such as Crizotinib. The small molecule Crizotinib is a selective inhibitor of the receptor tyrosine kinase ALK (anaplastic lymphoma kinase) and its oncogenic variants (ALK fusion gene and some mutations of ALK). Phases I and II trials showed the efficacy of Crizotinib in the treatment of locally advanced and metastatic NSCLC expressing ALK. Thereafter, randomized Phase III trial confirmed the significant superiority of Crizotinib versus standard chemotherapy in terms of progression free survival and objective response with good tolerance;therefore, it has been approved by the Food and Drug Administration (FDA) as the standard treatment for locally advanced and metastatic ALK-positive NSCLC.
文摘Background: Crizotinib is a tyrosine kinase inhibitor of ALK, MET and ROS1. In a safety database trial, it was suggested an association of Crizotinib with the development of renal cyst in patients with non-small-cell lung cancer (NSCLC). Aim: To report an uncommon side effect of Crizotinib in a patient with NSLC. Case Presentation: We report the case of a 68-year-old woman with NSCLC who developed bilateral progressive aseptic renal abscesses during Crizotinib treatment. Conclusion: Further studies may be necessary to determinate the risk of renal cyst development and the management of these complications.
文摘INTRODUCTION Non-small cell lung cancer（NSCLC）is a common malignant disease with an extremely poor prognosis.Lung cancer has been reported to metastasize to the eye in 0.2%to7%of patients based on clinical studies,and in 6%to 7%of patients based on postmortem histopathologic studies.
