Multiple laboratory evidences indicate that distinct variants of ALK translocations differ in their biochemical properties and responsiveness to ALK tyrosine kinase inhibitors (TKI). These data are supported by some Asian clinical studies, which showed improved responses to crizotinib in non-small cell lung cancer (NSCLC) patients carrying particular variants of ALK translocation.
This study retrospectively considered 64 Russian patients with ALK-rearranged NSCLC, who were treated by crizotinib (n = 23), ceritinib (n = 39) or alectinib (n = 2). ALK fusion variants were genotyped by PCR.
Median progression-free survival (PFS) approached to 18 and 21 months in subjects with “short” (v.3a/b, v.5a/b) vs. “long” (TAPE-domain containing) fusion variants (p = 0.783), respectively; similar data were obtained while comparing EML4/ALK variant 1 vs. other ALK translocations (19 and 21 months, respectively; p = 0.604). Objective response rates were also strikingly similar in the above groups (“short”: 88%, “long”: 77%, p = 0.479; variant 1: 76%, other translocations: 81%, p = 0.753). Furthermore, ALK variants did not influence the disease outcomes when patients treated by crizotinib and ceritinib were analyzed separately. Overall, PFS on ALK TKI did not depend on whether the drug was administered upfront or after chemotherapy. Ceritinib produced significantly longer PFS than crizotinib (p = 0.022).
This is the first non-Asian study evaluating the relationship between ALK fusion variants and response to ALK TKI. Although being larger in size as compared to published data sets, it failed to confirm the role of the type of ALK translocation in determining the treatment outcome.
Clinical trial identification
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This study has been supported by the Russian Scientific Fund.
All authors have declared no conflicts of interest.