ALK testing methods: is there a winner or loser?

ABSTRACT

Introduction: Anaplastic lymphoma kinase (ALK) is one of the most attractive molecular targets for the treatment of patients with non-small-cell lung cancer. Treatment with ALK inhibitors is recognized as the standard-of-care for patients with ALK gene rearrangements, but it is important to appropriately select patients who will benefit from such treatment.

Areas covered: In this article, we review the evidence regarding ALK testing. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and reverse transcription polymerase chain reaction (RT-PCR) are the representative methods for detecting ALK gene fusions. Among these diagnostic modalities, IHC in particular exhibits high sensitivity and specificity for the detection of ALK fusions when appropriately applied and interpreted.

Expert commentary: Discrepancies have been reported between the results of IHC and FISH. However, it was revealed that patients with IHC-positivity and FISH-negativity may respond to alectinib, indicating that IHC can be used as a stand-alone method from a clinical standpoint for the identification of patients eligible for treatment with ALK inhibitors. In addition, differences between ALK variants have been reported to affect the prognosis and efficacy of ALK inhibitor-based treatments, and RT-PCR will likely increase in importance as a complementary tool.

KEYWORDS:

• ALK
• FISH
• IHC
• non-small-cell lung cancer
• RT-PCR

Acknowledgments

We thank Natasha Beeton-Kempen, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

Declaration of interest

T. Seto has potential conflicts of interest to disclose with Astellas Pharma, Pfizer Japan, Novartis Pharma, Takeda Pharmaceutical, and Chugai Pharmaceutical. T. Seto reports grants from Bayer Yakuhin, Eisai, Merck Serono, Novartis Pharma, and Verastem; personal fees from Bristol-Myers Squibb, Kyowa Hakko Kirin, Mochida Pharmaceutical, Nippon Kayaku, Ono Pharmaceutical, Roche Singapore, Sanofi, Showa Yakuhin, and Taiho Pharmaceutical; grants and personal fees from AstraZeneca, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Kissei Pharmaceutical, MSD, Nippon Boehringer Ingelheim, Pfizer Japan, Yakult Honsha, outside the submitted work. The other authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer of this manuscript declares being a full time employee of NEO New Oncology, a company developing hybridd-capture based NGS diagnostics. The other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.P

Additional information

Funding

This paper was not funded