TEST:

VENTANA ALK (D5F3) CDx Assay

On April 18, 2024, the Food and Drug Administration approved alectinib (Alecensa, Genentech, Inc.) for adjuvant treatment following tumor resection in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test.

LORBRENA is a kinase inhibitor indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.

ALECENSA is a kinase inhibitor indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.

ZYKADIA is a kinase inhibitor indicated for the treatment of adults with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test

XALKORI is a kinase inhibitor indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test

The rate of investigator-assessed progression-free survival was significantly higher with alectinib than with crizotinib (12-month event-free survival rate, 68.4% [95% confidence interval (CI), 61.0 to 75.9] with alectinib vs. 48.7% [95% CI, 40.4 to 56.9] with crizotinib; hazard ratio for disease progression or death, 0.47 [95% CI, 0.34 to 0.65]; P<0.001); the median progression-free survival with alectinib was not reached. The results for independent review committee-assessed progression-free survival were consistent with those for the primary end point.

Of the 65 patients with ALK-positve NSCLC who underwent treatment failure of crizotinib, 43 (66.2%) received alectinib and 22 (33.8%) received ceritinib...The median follow-up duration was 16.8 months and 32.0 months in the alectinib and ceritinib groups, respectively....The tumor response was estimable in 63 patients (41 treated with alectinib and 22 treated with ceritinib), with the CR and PR being 2.4 and 70.8%,respectively, in the alectinib group and the PR being 50% in the ceritinib group.

Of the 65 patients with ALK-positve NSCLC who underwent treatment failure of crizotinib, 43 (66.2%) received alectinib and 22 (33.8%) received ceritinib...The median follow-up duration was 16.8 months and 32.0 months in the alectinib and ceritinib groups, respectively....The tumor response was estimable in 63 patients (41 treated with alectinib and 22 treated with ceritinib), with the CR and PR being 2.4 and 70.8%,respectively, in the alectinib group and the PR being 50% in the ceritinib group.

Of the 65 patients with ALK-positve NSCLC who underwent treatment failure of crizotinib, 43 (66.2%) received alectinib and 22 (33.8%) received ceritinib as the subsequent treatment….Patients receiving alectinib treatment, compared to ceritinib, showed a similar 12-month PFS rate (61.0% [95% confidence interval, 47.1 to 78.9%] vs. 54.5% [95% CI, 37.3 to 79.9%]); HR for disease progression or death, 0.61 (95% CI, 0.31–1.17; p = 0.135) and median PFS (20.1 vs. 13.9 months; log-rank test p = 0.100, Fig. 1a) than those receiving ceritinib treatment....A numerically higher response rate was noted in the patients who received alectinib treatment (73.2 vs. 50.0%, p = 0.096; Table 2).

A total of 20 cases received an ALK inhibitor as first- or second-line treatment which included 11 with a partial response (PR), four with SD, and five with PD. The DCR and ORR was 75.0% (15/20) and 55.0% (11/20), respectively….Patients with ALK-rearranged SCC obtained clinical benefit from ALK-inhibitor therapy, especially those who were non-smokers and whose tumors had been identified by IHC+/FISH+.

A 54-year-old, non-smoking woman was diagnosed as stage ⅣB adenocarcinoma with widespread bone metastasis (cT4N2M1c) in our hospital. Immunohistochemistry (Ventana D5F3 antibody) result showed the presence of ALK rearrangement; and next-generation sequencing assay (NGS) indicated EML4-ALK fusion (E6:A20) with concurrent CCDC148-ALK (C1:A20), PKDCC-ALK (Pintergenic:A20)and VIT-ALK (V15:A20) fusions....The administration of a first-generation ALK inhibitor crizotinib was then initiated and the disease was stable for 25 months without recurrence of ILD.

Pathological analysis of bronchoscopy biopsy tissue confirmed lung adenocarcinoma….The presence of EML4-ALK gene fusion and an ALK exon 23 F1174L and S1189C mutation was identified by targeted next-generation sequencing... alectinib was recommended on 24 July 2019....his condition deteriorated again during alectinib therapy in the second month...

Pathological analysis of bronchoscopy biopsy tissue confirmed lung adenocarcinoma….The presence of EML4-ALK gene fusion and an ALK exon 23 F1174L and S1189C mutation was identified by targeted next-generation sequencing...the patient was switched to ceritinib (150 mg, QD) for nearly 2 months. However, the chest CT assessment indicated PD after ceritinib...

Pathological analysis of bronchoscopy biopsy tissue confirmed lung adenocarcinoma….The presence of EML4-ALK gene fusion and an ALK exon 23 F1174L and S1189C mutation was identified by targeted next-generation sequencing...The patient received crizotinib (250 mg, BID) as first-line targeted therapy for approximately 2.5 months...progressive disease (PD) was diagnosed according to chest CT...

A 27-year-old man was diagnosed with a stage IIIAcT3N2M0 (7thUICC/AJCC) upper left lung adenocarcinoma harboring EML4-ALK fusion...Five months after SRS, the intracranial oligometastasis showed a complete response based on the RECIST 1.1 criteria...The patient’s overall survival (OS) time is currently 68 months.