ALK Inhibitors in the Treatment of ALK Positive NSCLC
Background: ALK inhibitors have shown positive advance in the treatment of ALK+ NSCLC. They have achieved better results in prolonging the progression free survival and improving quality of life in comparison to chemotherapy. We have assembled the evidence related to the efficacy and safety of these...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2018.00557/full |
| _version_ | 1819105978027606016 |
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| author | Muhammad Khan Muhammad Khan Jie Lin Guixiang Liao Yunhong Tian Yingying Liang Rong Li Mengzhong Liu Mengzhong Liu Yawei Yuan Yawei Yuan |
| author_facet | Muhammad Khan Muhammad Khan Jie Lin Guixiang Liao Yunhong Tian Yingying Liang Rong Li Mengzhong Liu Mengzhong Liu Yawei Yuan Yawei Yuan |
| author_sort | Muhammad Khan |
| collection | DOAJ |
| description | Background: ALK inhibitors have shown positive advance in the treatment of ALK+ NSCLC. They have achieved better results in prolonging the progression free survival and improving quality of life in comparison to chemotherapy. We have assembled the evidence related to the efficacy and safety of these agents in the treatment of ALK positive NSCLC.Materials and Methods: A comprehensive search was conducted using electronic databases of PubMed, Medline and Cochrane Library to identify the studies involving comparison of ALK inhibitors to chemotherapy and Next generation ALK inhibitors to crizotinib. PFS was the primary outcome while other outcomes like ORR, adverse events, quality of life and OS were also analyzed and compared. Hazard ratios and odds ratios obtained were analyzed using fixed effect or random effects model in Review Manager Software.Results: A total of 12 studies (n = 3,297) met the criteria for inclusion in this review and meta-analysis. ALK inhibitors including crizotinib, ceritinib and alectinib revealed significantly better PFS (HR 0.42 [0.35, 0.50; p < 0.00001]), ORR (Overall OR 6.59 [4.86, 8.94; p < 0.00001] as compared to chemotherapy in the first line as well as second line treatment settings. Intracranial response rate was better with ALK inhibitors (ceritinib and alectinib) as compared to chemotherapy OR 6.51 [2.86, 14.83; p < 0.00001]. No significant increase in grade 3 or 4 adverse events was observed with crizotinib (OR 1.21 [0.82, 1.77; p = 0.34]) or ceritinib (OR 1.49 [0.86, 2.57; p = 0.17]) when compared to chemotherapy individually. Quality of life indicators assessed were significantly improved with ALK inhibitors. Next generation agents (ceritinib, alectinib and brigatinib) revealed significant improvement in PFS (HR 0.50 [0.43, 0.57; p < 0.00001]), ORR (OR 1.57 [1.21, 2.04; p = 0.0006]) in comparison to crizotinib. Next generation agents (Alectinib and brigatinib) yielded better response intra-cranially than crizotinib in terms of objective response rate (OR 5.87 [3.49, 9.87; p < 0.00001]) and time to CNS progression (HR 0.25 [0.13, 0.46; p < 0.0001]). Alectinib by far resulted in fewer adverse events than chemotherapy or crizotinib.Conclusions: Overall ALK inhibitors are safe and effective treatment option in ALK+ non-small cell lung cancer. Of the ALK inhibitors, Next generation agents in particular alectinib and brigatinib are safer and more effective intra-cranially and can be preferred as first option. |
| first_indexed | 2024-12-22T02:30:50Z |
| format | Article |
| id | doaj.art-46b0aa1fa6644988bba17b40f3be9497 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-22T02:30:50Z |
| publishDate | 2019-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-46b0aa1fa6644988bba17b40f3be94972022-12-21T18:41:54ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-01-01810.3389/fonc.2018.00557429912ALK Inhibitors in the Treatment of ALK Positive NSCLCMuhammad Khan0Muhammad Khan1Jie Lin2Guixiang Liao3Yunhong Tian4Yingying Liang5Rong Li6Mengzhong Liu7Mengzhong Liu8Yawei Yuan9Yawei Yuan10Department of Radiation Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, ChinaDepartment of Oncology, First affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Radiation Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, ChinaDepartment of Radiation Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, ChinaDepartment of Radiation Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, ChinaDepartment of Radiation Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, ChinaDepartment of Radiation Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, ChinaDepartment of Radiation Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, ChinaDepartment of Radiation Oncology, Sun Yat-sen University Cancer Center, Sun Yat-sen Medical University, Guangzhou, ChinaDepartment of Radiation Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, ChinaDepartment of Radiation Oncology, Sun Yat-sen University Cancer Center, Sun Yat-sen Medical University, Guangzhou, ChinaBackground: ALK inhibitors have shown positive advance in the treatment of ALK+ NSCLC. They have achieved better results in prolonging the progression free survival and improving quality of life in comparison to chemotherapy. We have assembled the evidence related to the efficacy and safety of these agents in the treatment of ALK positive NSCLC.Materials and Methods: A comprehensive search was conducted using electronic databases of PubMed, Medline and Cochrane Library to identify the studies involving comparison of ALK inhibitors to chemotherapy and Next generation ALK inhibitors to crizotinib. PFS was the primary outcome while other outcomes like ORR, adverse events, quality of life and OS were also analyzed and compared. Hazard ratios and odds ratios obtained were analyzed using fixed effect or random effects model in Review Manager Software.Results: A total of 12 studies (n = 3,297) met the criteria for inclusion in this review and meta-analysis. ALK inhibitors including crizotinib, ceritinib and alectinib revealed significantly better PFS (HR 0.42 [0.35, 0.50; p < 0.00001]), ORR (Overall OR 6.59 [4.86, 8.94; p < 0.00001] as compared to chemotherapy in the first line as well as second line treatment settings. Intracranial response rate was better with ALK inhibitors (ceritinib and alectinib) as compared to chemotherapy OR 6.51 [2.86, 14.83; p < 0.00001]. No significant increase in grade 3 or 4 adverse events was observed with crizotinib (OR 1.21 [0.82, 1.77; p = 0.34]) or ceritinib (OR 1.49 [0.86, 2.57; p = 0.17]) when compared to chemotherapy individually. Quality of life indicators assessed were significantly improved with ALK inhibitors. Next generation agents (ceritinib, alectinib and brigatinib) revealed significant improvement in PFS (HR 0.50 [0.43, 0.57; p < 0.00001]), ORR (OR 1.57 [1.21, 2.04; p = 0.0006]) in comparison to crizotinib. Next generation agents (Alectinib and brigatinib) yielded better response intra-cranially than crizotinib in terms of objective response rate (OR 5.87 [3.49, 9.87; p < 0.00001]) and time to CNS progression (HR 0.25 [0.13, 0.46; p < 0.0001]). Alectinib by far resulted in fewer adverse events than chemotherapy or crizotinib.Conclusions: Overall ALK inhibitors are safe and effective treatment option in ALK+ non-small cell lung cancer. Of the ALK inhibitors, Next generation agents in particular alectinib and brigatinib are safer and more effective intra-cranially and can be preferred as first option.https://www.frontiersin.org/article/10.3389/fonc.2018.00557/fullanaplastic lymphoma kinase (ALK)non-small cell lung cancer (NSCLC)molecular targeted agentschemotherapyprogression free survival (PFS)quality of life (Qol) |
| spellingShingle | Muhammad Khan Muhammad Khan Jie Lin Guixiang Liao Yunhong Tian Yingying Liang Rong Li Mengzhong Liu Mengzhong Liu Yawei Yuan Yawei Yuan ALK Inhibitors in the Treatment of ALK Positive NSCLC Frontiers in Oncology anaplastic lymphoma kinase (ALK) non-small cell lung cancer (NSCLC) molecular targeted agents chemotherapy progression free survival (PFS) quality of life (Qol) |
| title | ALK Inhibitors in the Treatment of ALK Positive NSCLC |
| title_full | ALK Inhibitors in the Treatment of ALK Positive NSCLC |
| title_fullStr | ALK Inhibitors in the Treatment of ALK Positive NSCLC |
| title_full_unstemmed | ALK Inhibitors in the Treatment of ALK Positive NSCLC |
| title_short | ALK Inhibitors in the Treatment of ALK Positive NSCLC |
| title_sort | alk inhibitors in the treatment of alk positive nsclc |
| topic | anaplastic lymphoma kinase (ALK) non-small cell lung cancer (NSCLC) molecular targeted agents chemotherapy progression free survival (PFS) quality of life (Qol) |
| url | https://www.frontiersin.org/article/10.3389/fonc.2018.00557/full |
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