Vandetanib in patients with previously treated RET-rearranged advanced non-small-cell lung cancer (LURET): an open-label, multicentre phase 2 trial (original) (raw)

“…In the case of the RET fusion product, cells expressing KIF5B-RET were shown to have similar sensitivity to the RET-TKIs vandetanib and lenvatinib, when compared with those expressing CCDC6-RET or NCOA4-RET (36, 37). However, a phase II clinical trial investigating the effect of vandetanib in NSCLC with RET fusion genes demonstrated that the effect of vandetanib was different in patients expressing KIF5B-RET or CCDC6-RET, with response rates of 20% and 83%, respectively (38), suggesting that the effect of targeted drugs in patients may differ depending on the specific fusion partner in the oncogenic gene rearrangement. The discrepancy of results between the in vitro study and the clinical trial may indicate a limitation of the in vitro model using cells transfected with target genes.…”

Section: Discussionmentioning

“…There is no current standard test for identification of RET fusions in patient samples, but fish or targeted capture/ngs are potential methods. At this point, there are no approved therapies for RET in nsclc, although multiple studies with RET inhibitors are underway [68][69][70][71] .…”

Section: Ret Mutationsmentioning

“…Two phase II studies in Japanese and Korean population were recently reported. The LURET study (UMIN000010095) was a nationwide effort conducted in Japan, which investigated the role of vandetanib in 17 advanced NSCLC patients (57). The results were encouraging, nine (47%) of the 17 patients responded, while the median PFS was 4.7 months.…”

Section: Ret Rearrangementsmentioning

“…Although the small sample size of these studies no doubt contributed to the range of outcomes observed, differences in pre-screening strategies can also impact on responses. Notably, the Japanese study enrolled patients from a national molecular screening program (LC-SCRUM) where patients underwent RT-PCR and were eligible only if confirmed by FISH (57), while the Korean study screened EGFR wild type, ALK non-rearranged patients with breakapart FISH, and the results were subsequently confirmed using one of the following tests, IHC, RT-PCR or targeted deep sequencing (58). In the Japanese study, the adjusted ORR following vandetanib was 83% among 6 patients with CCDC6-RET and 20% among 10 patients with KIFB-RET fusion (57).…”

Section: Ret Rearrangementsmentioning

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