FGF19 amplification

One patient with H-CCK showing CDK4 amplification was treated by Palbociclib, he experienced a partial radiological response during 16 months. Another patient with H-CCK and high HER2 overexpression and a high homologous recombination score was treated by Trastuzumab/Olaparib with had a stable disease at the first imaging evaluation...The remaining six treated patients (6 HCC) harbored a progressive disease including three patients treated by Trametinib, two by Everolimus and one by Olaparib. Molecular based guided therapy is feasible in patients with HCC and H-CCK and progressing under atezolizumab/bevacizumab. Forty five percent received a therapy adapted to a genomic alteration with a clinical benefit in one third of them.

Another subgroup was defined by both CTNNB1ex3 and TP53 mutations, which presented mixed features of CTNNB1ex3 HCC and TP53-mut HCC. In clinicopathological and genomic level, this subgroup presented the characteristics of TP53-mut HCCs with an enrichment of HBV infection, higher Edmonson III-IV grade and CCND1-FGF19 amplification, more copy-number events and high proportion of whole-genome duplication and was associated with poor prognosis, while in the transcriptomic level, CTNNB1ex3; TP53 HCC clustered with CTNNB1ex3 HCCs.ConclusionWe refined the molecular classifications of HCC, which may be useful for therapeutic strategy.

We reported a novel rare ALK fusion SEC31A: EXON20~ALK: exon20 and showed the effectiveness of crizotinib against the fusion. This study provided strong evidence for the efficacy of ALK-TKI for rare ALK fusion.

FGFR1, FGF19, FGF23, FGF3, FGF4, and FGF6 amplifications were statistically different across subtypes (most prevalent in HR+/HER2- and HR+/HER2+) and metastatic sites (most prevalent in liver and bone metastases). The prevalence in HR+ subtypes lend support to the role of FGF in endocrine resistance.

We found that Src is essential for the endosomal delivery of the FGFR4 signaling complex in HCC. Our findings provide a scientific rationale for repurposing Src inhibitors for the treatment of HCCs in which the FGFR4 pathway is activated.

P1/2, N=386, Active, not recruiting, Taiho Oncology, Inc. | Trial completion date: May 2021 --> Dec 2021 | Trial primary completion date: Dec 2019 --> May 2021

The results suggest that ctDNA METex14 undetectable at baseline or clearance upon savolitinib treatment may define favorable treatment outcome. Confirmation of this finding and the predictive value of the ctDNA with larger sample size is desirable.

Our study highlights the heterogeneity both in the primary molecular landscape and acquired alterations in EGFR-mutated NSCLCs, which might play a role in determining the clinical efficacy of EGFR-TKIs. We also revealed the differential prognostic role of TP53 mutation in patients treated with the 1st or 2nd generation of EGFR-TKI. Our study also suggests that EGFR-mutant and TP53-WT patients may benefit more from combinatorial treatment consisting of EGFR-TKI and bevacizumab, highlighting the importance of further stratifying EGFR-mutant patients.