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Efficacy of crizotinib in ALK mutant non-small cell lung cancers that are positive by IHC but negative by FISH compared to FISH positive cases

In Indian Journal of Cancer
By: Zanwar S.
Contributor(s): Noronha V | Joshi A | Patil VM | Kaushal R | Chougule A | Janu A | Mahajan A | Kapoor A | Prabhash K [Corresponding author].
Material type: materialTypeLabelArticlePublisher: 2018Description: .Subject(s): Anaplastic lymphoma kinase positive | Crizotinib | Fluorescence in situ hybridization | Immunohistochemistry In: Indian Journal of CancerSummary: BACKGROUND: A small proportion of Non-Small Cell Lung Cancers (NSCLC) are detected with Anaplastic Lymphoma Kinase (ALK) mutation by immunohistochemistry (IHC) but are negative by Fluorescence in situ Hybridization (FISH). Data on responses and outcome of this subset of patients when treated with crizotinib is limited. We analyzed the outcomes of such patients who received crizotinib. PATIENTS AND METHODS: Demographics, treatment details, response to treatment, date of progression and date of death were collected for patients who were IHC positive and FISH negative for ALK mutation from a prospectively maintained database. Depending upon feasibility, patients received either platinum based doublet chemotherapy or the ALK inhibitor crizotinib as first line therapy. Outcomes were compared to our previously published historical cohort of FISH positive patients who were treated with crizotinib. RESULTS: Thirteen patients were detected to be IHC+/FISH- and out of these seven received crizotinib. Objective response rate for crizotinib was 57.15% with an estimated mean PFS of 9.6 months (95% CI 3.8 -15.5 months). The difference in ORR of ALK IHC+/FISH- when compared to our historical cohort of ALK FISH positive treated with crizotinib was not statistically significant (57.15% vs 69.8%; P = 0.265). Estimated mean and median PFS was similar between the two cohorts (median PFS 6.0 months vs 14 months; mean PFS 9.6 months versus 14.7 months; P = 0.467). CONCLUSION: NSCLCs positive for ALK mutation by IHC but not detected by FISH show good response to crizotinib and merit treatment with the same.
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Articles Articles Tata Memorial Hospital
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Address for correspondence: kprabhash1@gmail.com

BACKGROUND: A small proportion of Non-Small Cell Lung Cancers (NSCLC) are detected with Anaplastic Lymphoma Kinase (ALK) mutation by immunohistochemistry (IHC) but are negative by Fluorescence in situ Hybridization (FISH). Data on responses and outcome of this subset of patients when treated with crizotinib is limited. We analyzed the outcomes of such patients who received crizotinib. PATIENTS AND METHODS: Demographics, treatment details, response to treatment, date of progression and date of death were collected for patients who were IHC positive and FISH negative for ALK mutation from a prospectively maintained database. Depending upon feasibility, patients received either platinum based doublet chemotherapy or the ALK inhibitor crizotinib as first line therapy. Outcomes were compared to our previously published historical cohort of FISH positive patients who were treated with crizotinib. RESULTS: Thirteen patients were detected to be IHC+/FISH- and out of these seven received crizotinib. Objective response rate for crizotinib was 57.15% with an estimated mean PFS of 9.6 months (95% CI 3.8 -15.5 months). The difference in ORR of ALK IHC+/FISH- when compared to our historical cohort of ALK FISH positive treated with crizotinib was not statistically significant (57.15% vs 69.8%; P = 0.265). Estimated mean and median PFS was similar between the two cohorts (median PFS 6.0 months vs 14 months; mean PFS 9.6 months versus 14.7 months; P = 0.467). CONCLUSION: NSCLCs positive for ALK mutation by IHC but not detected by FISH show good response to crizotinib and merit treatment with the same.

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