ALK In Non-small Cell Lung Cancer Research Articles

EE52 Cost-Effectiveness Analysis of Crizotinib Versus Chemoterapy for First Line Treatment of Non-Small Cell Lung Cancer Alk+, from the Brazilian Public Healthcare System Perspective

Lung cancer is one of the most prevalent cancers in men and women and has the highest mortality rate of all cancers except non-melanoma skin cancer. Approximately 85% of the cases are non-small cell lung cancer (NSCLC) and, among these, about 3% present the ALK+ translocation. The aim of this analysis is to compare effectiveness and incremental costs between crizotinib and standard chemotherapy in the ALK+ NSCLC treatment from the Brazilian public healthcare system perspective.

Low ALK FISH positive metastatic non-small cell lung cancer (NSCLC) patients have shorter progression-free survival after treatment with ALK inhibitors

ALK FISH assay guides clinical decision to initiate therapy with ALK inhibitors in patients with stage IV non-small cells lung cancer (NSCLC). In this single institution retrospective study, we investigated the association between the strength of ALK positivity and progression-free survival (PFS) We screened 4,829 patients tested for ALK rearrangement by FISH from 01/06/2012 to 06/30/2018 and included 66 stage IV NSCLC ALK positive patients, who were ALK inhibitor naïve, received an ALK inhibitor, and been followed at least 10 months to the study. The median PFS for cases high positive cases [≥=50% positive nuclei; n = 49] and low positive cases [16–49% positive nuclei; n = 17] is 16 months and 4 months respectively, and the hazard ratio is 2.89 [95 CI 1.34–6.2] (p = 0.0068). When cases are stratified according to cut-off ≥=30% positive nuclei, the median PFS for cases above (n = 55) and below the cut-off (n = 11) is 12 and 3 months, respectively and the hazard ratio is 9.60 [95 CI 2.63–35.04] (p < 0.0001) Patients with low FISH positive results have shorter PFS. Although a biological reason is plausible, false positivity may be a contributing factor. For low positive results, confirmation of the FISH result with an orthogonal technology is warranted.

Efficacy and safety of Crizotinib in patients with ALK positive non small cell lung cancer (NSCLC): Real-world findings.

e20636 Background: First or second line crizotinib has shown greater efficacy in clinical trials than chemotherapy in patients with NSCLC ALK positive and it was the first approved ALK inhibitor. However, there are limited data describing the use of crizotinib and its outcomes in real-world settings. Methods: This is a retrospective, observational study of patients crizotinib treated ALK positive metastatic NSCLC, who received treatment between 1 January 2013 and 30 november 2018. The primary objective was progression free survival (PFS); secondary objetives were overall survival (OS), response rates and toxicity. Results: Fifty-eight patients with NSCLC ALK+ were recollected, 33 women and 25 men. The median age was 61 years (25-88); 46.6% were never smokers, 31% were former smokers. The majority (96.6%) had confirmed adenocarcinoma histology and 25.9% had brain metastases at inicial treatment. Crizotinib was used as first line 55.2% and second line in 37.9%. Progression disease was the most frequent reason of discontinuation of crizotinib (74%) and in 5 patients was discontinued because of toxicity. The most frequent toxicities were edemas (37.9%), increased transaminases (27.5), diarrhea (24%) and nauseas (20%). Grade 3-4 toxicities were present in 4 cases with increase transaminases, 1 case of neumonitis and 2 patients with diarrhea. The response rate was 63.8%. The median PFS was 12.66 months (95% CI :7.95- 17.38) and median OS was 23.36 months (95%CI: 16.29-30.44).In patients with brain metastases (15) the response rate was 46.6% and median OS decrease to 15.36 months (95%CI: 0.1-30.8). Conclusions: Our findings indicate that the results of crizotinib in the real world are consistent or sightly improved with prior clinical trial in PFS and OS, despite our sample includes patients for first line and second/later line crizotinib and ¼ of patients had brain metastasic at crizotinib initiation.

A study of EGFR wild-type non-small cell lung cancer ALK genetic mutation

Background: the positive rate and clinicopathological features of EML4-ALK, the relationship between EGFR mutations in non-small cell lung cancer (NSCLC) patients are the state of confusion, automatic immunohistochemistry to detect the expression of ALK protein, to provide reference for clinical diagnosis and treatment.

Occurrence of ALK fusions in cancers other than non-small cell lung cancer in a wide variety of tumor types and response to anti-ALK targeted therapy.

11595 Background: Genomic fusions of the anaplastic lymphoma kinase gene ( ALK) are an established therapy target for patients with non-small cell lung cancer (NSCLC), but are not well-characterized in non-NSCLC malignancies. Methods: Comprehensive genomic profiling (CGP) of 92,784 clinically advanced malignancies was performed using a hybrid-capture, adaptor ligation based NGS assay to a mean coverage depth of &gt;600X. Tumor mutational burden (TMB) was calculated from a minimum of 1.1 Mb of sequenced DNA. Results: 17,127/92,784 (18.5%) were NSCLC and 75,657 (81.5%) were non-NSCLC. Of the 697 (0.8%) of cases with ALK fusions, 554 (79%) were identified in NSCLC and 143 (21%) in non-NSCLC including 67 carcinomas; 39 sarcomas including 30 non-uterine and uterine leiomyosarcomas and inflammatory myofibroblastic tumors; 24 in hematolymphoid malignancies including non-Hodgkins lymphomas, myelomas and histiocytic malignancies; 3 in gliomas; 2 each in mesotheliomas, neuroblastomas and undifferentiated malignancies and 1 in melanoma. ALK fusions were significantly more frequently identified in NSCLC (3.2%) than in non-NSCLC (p&lt;0.0001). The non-NSCLC ALK fusion positive patients were significantly older (p&lt;0.0001) and more often female (p&lt;0.0001) than the NSCLC ALK fusion positive patients. At 84%, the more frequent finding of EML4 as the fusion partner in the NSCLC patients versus non-NSCLC patients at 31% was significant (p&lt;0.0001). ALK fusion positive non-NSCLC had significantly lower TMB (mean 5.01 mutations/Mb) than non- ALK altered non-NSCLC (p=0.006). Non-NSCLC ALKfusion positive cases responding to ALK inhibitors will be presented. Conclusions: In non-NSCLC patients ALK fusions are rare and found in both epithelial and mesenchymal malignancies. Initial evidence strongly suggests that anti-ALK therapies can be effective in ALK fusion driven non-NSCLC .