Crizotinib-treated ALK IHC-positive advanced NSCLC is associated with an unfavourable prognosis when FISH negative

ALK rearrangement detection using fluorescence in situ hybridisation (FISH) or dichotomous immunohistochemical staining (IHC) is a standard test to identify patients with NSCLC eligible for treatment with ALK inhibitors [7].

A European, prospective, multicentre study compared response to treatment with crizotinib in ALK FISH+ and ALK FISH- in patients with ALK IHC+. Central collection of stage 4 ALK IHC+ NSCLC cases treated with crizotinib took place from April 2014 to November 2017. Slides were centrally validated for ALK IHC and ALK FISH. Monthly recording showed that of 3,523 registered ALK IHC tests, 94 (2.6%) were ALK IHC+; less than 0.01% were ALK IHC+ FISH- cases. Local ALK FISH analysis identified 46 concordant (ALK IHC+/FISH+) cases and 18 that were discordant (ALK IHC+/FISH-).

Central validation in Antwerp, Belgium, found 37 concordant and 6 discordant cases, 5 of which had follow-up. Limited tissue in the biopsy samples hampered validation. Time to treatment was the same for concordant and discordant cases (HR 0.78; P=0.64). The same was true for local or validated ALK testing (HR 2.2; P=0.16). But, after central validation, overall survival was significantly longer for patients with concordant cases than discordant ones (HR 4.5; P=0.010; see Figure). Local testing found otherwise (HR 1.7; P=0.44)

Figure: Overall survival based on central testing