Crizotinib was recently approved by the US FDA for the treatment of advanced non–small cell lung cancer (NSCLC) harboring the ALK (anaplastic lymphoma kinase) gene rearrangement. To ensure identification of patients most likely to benefit, the FDA approved crizotinib concurrently with a companion diagnostic test—the Vysis ALK Break Apart FISH Probe Kit. This kit was used in 1 of the 2 pivotal trials leading to the FDA approval of crizotinib and has become the gold standard for detecting ALK rearrangement in NSCLC. Although ALK FISH is clinically validated, the assay can be technically challenging and costly. Therefore, other diagnostic modalities are being explored, including immunohistochemistry (IHC) and reverse transcriptase–polymerase chain reaction. This article provides an overview of the diagnostic assays available for detecting ALK rearrangement. Each assay, including ALK FISH, has its strengths and weaknesses. Recent work with commercially available ALK antibodies suggests that IHC-based tests may represent a reliable and cost-effective screening strategy; however, large multicenter studies comparing IHC with FISH are needed to validate ALK IHC. While ALK FISH remains the current standard for diagnosing ALK positivity, large-scale screening of patients with newly diagnosed advanced NSCLC, as recommended by NCCN, may require development and validation of alternative screening strategies, such as combination IHC and FISH.
Alice T. Shaw, Benjamin Solomon and Mari Mino Kenudson
Damien Urban, Danny Rischin, Christopher Angel, Ieta D’Costa and Benjamin Solomon
Salivary duct carcinoma (SDC) is a rare, aggressive salivary gland malignancy with limited evidence guiding standard treatment. SDC is known to overexpress the androgen receptor, with only a handful of cases reporting responses to androgen blockade. This report presents a case of SDC responding to multiple lines of androgen blockade, including a rapid response to abiraterone, a CYP17 inhibitor effective in prostate cancer. This case represents the first published report of SDC responding to abiraterone and illustrates that androgen receptor expressing SDC may be treated with multiple lines of androgen blockade, including newer agents such as abiraterone. This case suggests that SDC may continue to be androgen-dependent after progression on androgen deprivation, which is analogous to prostate cancer.
Annette M. Lim, Graham R. Taylor, Andrew Fellowes, Laird Cameron, Belinda Lee, Rodney J. Hicks, Grant A. McArthur, Christopher Angel, Benjamin Solomon and Danny Rischin
The efficacy of targeted monotherapy for BRAF V600E-positive anaplastic thyroid carcinomas (ATC) is not established. We report 2 cases of BRAF V600E-positive ATC treated with a BRAF inhibitor. A 49-year-old woman with a T4bN1bM0 ATC manifested symptomatic metastatic disease 8 weeks after radical chemoradiotherapy. Within 1 month of BRAF inhibitor monotherapy, a complete symptomatic response was observed, with FDG-PET scan confirming metabolic and radiologic response. Treatment was terminated after 3 months because of disease progression. The patient died 11 months after primary diagnosis. A 67-year-old man received first-line BRAF inhibitor for a T4aN1bM0 ATC. Within 10 days of treatment his pain had stabilized and his tumor had clinically halved in size. Stable disease was achieved for 11 weeks but the patient died 11 months after diagnosis because of disease progression. BRAF inhibitor monotherapy in ATC may obtain clinical benefit of short duration. Upfront combination therapy should be investigated in this patient subgroup.