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BIOMARKER:

FGFR1 amplification

i
Other names: FGFR1, BFGFR, CD331, CEK, FLG, FLT2, H2, H3, H4, H5, KAL2, N-SAM, Fibroblast growth factor receptor 1
Entrez ID:
12d
Real-World Data and Clinical Implications of Next-Generation Sequencing (NGS)-Based Analysis in Metastatic Breast Cancer Patients. (PubMed, Int J Mol Sci)
Of these, nine received treatment with a molecular target drug: eight patients with a mutation of the PIK3CA gene were treated with alpelisib and fulvestrant; one patient with FGFR1/2 amplifications received TAS120. The growing number of detectable mutations and increased accessibility of the test may lead to a greater number of potential therapeutic implications for the NGS assay. Perspectives suggest that NGS analysis can be implemented in daily clinical practice, particularly in contexts where a Molecular Tumor Board (MTB) is active.
Retrospective data • Journal • Real-world evidence • Next-generation sequencing • Real-world • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR1 (Fibroblast growth factor receptor 1)
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HER-2 positive • PIK3CA mutation • FGFR1 amplification • FGFR2 amplification
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Piqray (alpelisib) • fulvestrant • Lytgobi (futibatinib)
23d
Prevalence of fibroblast growth factor receptor (FGFR) alterations (alts) and programmed death-ligand 1 (PD-L1) expression (exp) in Chinese solid tumor patients (pts) (AACR 2024)
BALVERSA (erdafitinib), a selective pan-FGFR kinase inhibitor, has shown clinical activity against FGFR altered solid tumors in pts who exhausted standard treatment options... The large Chinese solid tumor cohort analysis showed comparable FGFR alts prevalence between Chinese and Western population. Differences in relationship between FGFR alts and PD-L1 expression across tumor types reflect the differential role of predominant FGFR types in each tumor type.
Clinical • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR (Fibroblast Growth Factor Receptor)
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PD-L1 expression • PD-L1 overexpression • FGFR1 amplification • FGFR1 expression
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PD-L1 IHC 22C3 pharmDx • MSK-IMPACT
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Balversa (erdafitinib)
1m
Pemigatinib for the Treatment of Metastatic or Unresectable Colorectal Cancer Harboring FGFR Alterations (clinicaltrials.gov)
P2, N=14, Active, not recruiting, Academic and Community Cancer Research United | N=24 --> 14
Enrollment change • Metastases
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FGFR1 amplification
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Pemazyre (pemigatinib)
1m
Sunitinib in Patients With Breast Cancer With FGFR1 or FGFR2 Amplifications or Mutations: Results From the Targeted Agent and Profiling Utilization Registry Study. (PubMed, JCO Precis Oncol)
Sunitinib did not meet prespecified criteria to declare a signal of antitumor activity in patients with BC with either FGFR1 or FGFR2 alterations. Other treatments and clinical trials should be considered for these patient populations.
Journal
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FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1)
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FGFR1 amplification • FGFR2 mutation • FGFR2 amplification
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Sutent (sunitinib)
1m
Whole-Genome Sequencing Analysis of Male Breast Cancer Unveils Novel Structural Events and Potential Therapeutic Targets. (PubMed, Mod Pathol)
Our results demonstrate unique genetic markers and potential treatment targets in MaBC, thereby underlining the necessity of tailoring treatment strategies for this under-studied patient population. These WGS-based findings add to the growing knowledge of MaBC genomics and highlight the need to expand research on this type of cancer.
Journal • Tumor mutational burden • BRCA Biomarker
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ER (Estrogen receptor) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • FGFR1 (Fibroblast growth factor receptor 1) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • FAT1 (FAT atypical cadherin 1) • ARID2 (AT-Rich Interaction Domain 2) • GATA3 (GATA binding protein 3)
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TMB-H • HRD • FGFR1 amplification • HRD signature
1m
Fulvestrant, Palbociclib and Erdafitinib in ER+/HER2-/FGFR-amplified Metastatic Breast Cancer (clinicaltrials.gov)
P1, N=35, Active, not recruiting, Vanderbilt-Ingram Cancer Center | Trial completion date: Dec 2023 --> Sep 2024
Trial completion date • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR4 (Fibroblast growth factor receptor 4) • FGF23 (Fibroblast Growth Factor 23)
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HER-2 negative • FGFR1 amplification • FGFR3 amplification • FGFR4 amplification • FGFR amplification
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Ibrance (palbociclib) • Balversa (erdafitinib) • fulvestrant
2ms
Real-world clinical utility of next-generation sequencing ctDNA for patients with advanced lung squamous cell carcinoma (ELCC 2024)
Conclusions NGS-ctDNA provided clinically informative results for 26% of pts with advanced lung SCC, including 6% for whom targeted therapies are available in routine practice or clinical trials (4% ESMO ESCAT tier I and 2% ESMO ESCAT tier IIB). These results suggest that molecular profiling, including plasma NGS testing, should be considered in this population.
Real-world evidence • Clinical • Next-generation sequencing • Circulating tumor DNA • Real-world • Metastases
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • FGFR1 (Fibroblast growth factor receptor 1) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)
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TP53 mutation • BRAF V600E • BRAF V600 • EGFR exon 19 deletion • KRAS G12D • EGFR amplification • KRAS G12V • FGFR1 amplification • ALK fusion • KRAS G12R • KRAS G12A • KRAS G12 • KRAS G13 • KRAS amplification • FGFR1 fusion • NRAS G12 • NRAS G13 • KRAS G13C • EGFR fusion • KRAS G61 • KRAS deletion
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InVisionFirst®-Lung
2ms
Identification of Piperazinyl-Difluoro-indene Derivatives Containing Pyridyl Groups as Potent FGFR Inhibitors against FGFR Mutant Tumor: Design, Synthesis, and Biological Evaluation. (PubMed, J Med Chem)
Moreover, compound (S)-23 exhibited favorable pharmacokinetic properties, low potential for drug-drug interactions, and very potent antitumor activity in MFE-296 xenograft mouse models with a TGI of 99.1% at the dose of 10 mg/kg. These findings demonstrate that compound (S)-23 is a potential therapeutic agent for FGFR mutant tumors.
Journal
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FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR4 (Fibroblast growth factor receptor 4)
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FGFR1 amplification • FGFR2 mutation • FGFR2 fusion • FGFR2 amplification • FGFR mutation • FGFR1 fusion • FGFR3 fusion • FGFR4 mutation
3ms
NCCH2006/MK010 Trial (FORTUNE Trial) (clinicaltrials.gov)
P2, N=46, Active, not recruiting, National Cancer Center, Japan | Recruiting --> Active, not recruiting
Enrollment closed • Metastases
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR2 (Fibroblast growth factor receptor 2) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR4 (Fibroblast growth factor receptor 4) • NTRK (Neurotrophic receptor tyrosine kinase)
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EGFR mutation • BRAF mutation • NRAS mutation • BRAF V600 • FGFR1 amplification • FGFR2 mutation • FGFR2 fusion • FGFR mutation • FGFR2 N549K • FGFR1 fusion • FGFR3 fusion • FGFR2 P253R • FGFR2 K310R • FGFR3 Y375C • FGFR2 C382R • FGFR2 N549D • FGFR2 N549H • FGFR2 S252W • FGFR2 Y375C • FGFR3 G380R • FGFR3 K650E • FGFR2 W290C
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tasurgratinib (E7090)
3ms
Trial completion date • Trial primary completion date • Metastases
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • AXL (AXL Receptor Tyrosine Kinase) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SMAD4 (SMAD family member 4) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • FLT1 (Fms-related tyrosine kinase 1) • CDK6 (Cyclin-dependent kinase 6) • CCND3 (Cyclin D3) • TYRO3 (TYRO3 Protein Tyrosine Kinase) • NTRK (Neurotrophic receptor tyrosine kinase)
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KRAS mutation • EGFR mutation • BRAF mutation • NRAS mutation • BRAF V600 • FGFR1 amplification • CDKN2A deletion • HRAS mutation • PTPN11 mutation • CCND1 amplification • KRAS amplification • BRAF amplification
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Mekinist (trametinib) • Tafinlar (dabrafenib) • Alecensa (alectinib) • Cabometyx (cabozantinib tablet) • Stivarga (regorafenib) • Kisqali (ribociclib) • Ayvakit (avapritinib) • siremadlin (HDM201)
4ms
A novel intronic circular RNA circFGFR1 up-regulates FGFR1 by recruiting transcriptional activators P65/FUS and suppressing miR-4687-5p to promote prostate cancer progression. (PubMed, J Transl Med)
Overexpression of circFGFR1 is significantly correlated with higher tumor grade, Gleason score, and PSA level, and is a significant unfavorable prognosticator for CRPC-free survival (CFS) (RR = 3.277, 95% confidence interval: 1.192-9.009; P = 0.021). These findings unravelled novel mechanisms controlling FGFR1 gene expression by intronic circRNA and its potential clinicopathological utility as a diagnostic or therapeutic target.
Journal
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FGFR1 (Fibroblast growth factor receptor 1) • FUS (FUS RNA Binding Protein)
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FGFR1 amplification • FGFR1 overexpression • FGFR1 expression
5ms
Prediction of Resistance to Lu-PSMA Therapy by Assessment of Baseline Circulating Tumor DNA Biomarkers. (PubMed, J Nucl Med)
Lu-PSMA-617 and Lu-PSMA I&T (collectively termed Lu-PSMA) are currently being used for the treatment of selected metastatic castration-resistant prostate cancer (mCRPC) patients with PSMA PET-positive disease, but biomarkers for these agents remain incompletely understood... Our analyses indicate that ctDNA assays may contain specific biomarkers predictive of response or resistance for Lu-PSMA-treated mCRPC patients. Additional confirmatory studies are required before clinicians can use these findings to make personalized treatment decisions.
Journal • Circulating tumor DNA
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FGFR1 (Fibroblast growth factor receptor 1) • CCNE1 (Cyclin E1) • CDK12 (Cyclin dependent kinase 12)
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FGFR1 amplification • CCNE1 amplification • CDK12 mutation
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Pluvicto (lutetium Lu 177 vipivotide tetraxetan)
5ms
Phase I study of the FGFR inhibitor rogaratinib, fulvestrant and palbociclib in advanced hormone receptor-positive (HR+) breast cancer (BC) with FGFR1/2 amplification and/or overexpression (FGFR1/2+) (SABCS 2023)
Triple FGFR1/2, CDK4/6 and ER blockade appears safe at standard drug dosages and shows promising clinical activity in second-line HR+ FGFR1/2+ BC patients progressing on CDK4/6i plus AI.
P1 data • Metastases
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FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1) • FGF23 (Fibroblast Growth Factor 23)
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HR positive • FGFR1 amplification • FGFR2 amplification
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Ibrance (palbociclib) • fulvestrant • rogaratinib (BAY 1163877)
5ms
Unravelling the role of FGFR1 in innate immune sensing and endocrine resistance in breast cancer (SABCS 2023)
Furthermore, we found that the inhibition of FGFR kinase enhances the expression of IFN-alpha, IFN-beta, TLR7, and TLR9 in T47D cells when stimulated with the TLR7 agonist loxoribine. These results strongly suggest that FGFR1 functions as an innate checkpoint and may be exploited by tumor cells to dampen Type 1 interferon responses, thereby inhibiting antitumor immunity in hormone receptor-positive breast cancer.
IO biomarker
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ER (Estrogen receptor) • FGFR1 (Fibroblast growth factor receptor 1) • TLR9 (Toll Like Receptor 9) • IFNA1 (Interferon Alpha 1)
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HR positive • FGFR1 amplification • FGFR1 expression
5ms
Targeting fibroblast growth factor receptor (FGFR1) expression through G-quadruplex stabilization inhibits metastatic breast cancer (SABCS 2023)
Importantly, use of the G4-binding compound CX-5461 stabilized the FGFR1 G4 structure, blocked the transcriptional activity of the FGFR1 proximal promoter and decreased FGFR1 expression...In conclusion, consistent with the clinical observations our evaluation of FGFR kinase inhibitors validates the resistance to FGFR kinase inhibitors in MBC. Our findings indicate that targeting FGFR1 expression through G4 stabilization may be a potential strategy for MBC.
Metastases
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FGFR1 (Fibroblast growth factor receptor 1)
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FGFR1 amplification • FGFR1 expression
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pidnarulex (CX-5461)
5ms
Baseline genomic alterations and the activity of lasofoxifene (LAS) plus abemaciclib (Abema) in patients with ER+/HER2- metastatic breast cancer (mBC): the ELAINE 2 study (SABCS 2023)
Of the 29 patients (median age 60 yrs) enrolled, mutations in ESR1 were identified in 26 by Guardant360; all these 26 patients had received prior CDK4/6i, 21 (81%) prior fulvestrant, and 12 (46%) prior chemotherapy for mBC. Using Guardant360 ctDNA profiling from patients in ELAINE 2, we demonstrate that other baseline genomic alterations are frequently detected concurrently with mESR1 in the endocrine resistant setting, but without apparent compromise on the efficacy of LAS plus Abema. These results should be interpreted with caution considering the small numbers of patients and the exploratory nature of the analysis. The ELAINE 2 study suggests the potential of LAS plus Abema for treating ESR1-mutated, ER+/HER2- mBC in the post-CDK4/6i setting.
Clinical • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1)
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TP53 mutation • ER positive • HER-2 negative • PIK3CA mutation • FGFR1 amplification • ER mutation • CCND1 amplification • ESR1 mutation • ER positive + HER-2 negative • ER positive + ESR1 mutation + CCND1 amplification • ER positive + ESR1 mutation + FGFR1 amplification • ER positive + ESR1 mutation + PIK3CA mutation • ER positive + ESR1 mutation + TP53 mutation • CDK4 mutation
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Guardant360® CDx
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Verzenio (abemaciclib) • fulvestrant • Fablyn (lasofoxifene)
5ms
Final results from the phase 2, open-label FOENIX-MBC2 study: efficacy and safety of futibatinib in adult patients with locally advanced/metastatic HR+/HER2− breast cancer harboring high-level FGFR1 gene amplification (SABCS 2023)
Futibatinib plus fulvestrant showed antitumor activity in patients with advanced HR+/HER2− breast cancer with FGFR1 amplification progressing on prior CDK4/6 inhibitors, with a numerically higher ORR and doubling in PFS relative to historical fulvestrant results in post-CDK4/6 patients. The safety profile was consistent with those of the individual study drugs. Further biomarker work is ongoing.
Clinical • P2 data • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1)
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HR positive • HER-2 amplification • HER-2 negative • FGFR1 amplification
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fulvestrant • Lytgobi (futibatinib)
5ms
Somatic rearrangements causing oncogenic ectodomain deletions of FGFR1 in squamous cell lung cancer. (PubMed, J Clin Invest)
Thus, the genomic events shaping the architecture of the 8p11-p12 amplicon provide a mechanistic explanation for the emergence of FGFR1-driven squamous cell lung cancer. Specifically, FGFR1 ectodomain deficient and FGFR1-centered amplifications caused by tail-to-tail rearrangements are novel somatic genomic event, which might be predictive of therapeutically relevant FGFR1 dependency.
Journal
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FGFR1 (Fibroblast growth factor receptor 1)
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FGFR1 amplification • FGFR1 expression
6ms
A study of gene alterations in Asian patients with late stage and recurrent breast cancer (ESMO Asia 2023)
Of the 12 patients with PIK3CA mutation detected in liquid and/or tissue, 8 were detected in both tissue and liquid, 2 detected in tissue alone and 2 detected in liquid alone. Conclusions Liquid-based NGS can be applied in clinical practice to identified clinically important mutations in Asian patients with recurrent breast cancer (BC) and de novo stage IV metastatic BC.
Clinical • BRCA Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
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HER-2 amplification • PIK3CA mutation • FGFR1 amplification • FGFR2 amplification
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Guardant360® CDx
7ms
Genomic Alterations Associated with Estrogen Receptor Pathway Activity in Metastatic Breast Cancer Have a Differential Impact on Downstream ER Signaling. (PubMed, Cancers (Basel))
In conclusion, RNA sequencing identified a subgroup of patients with clear expression of ESR1 and its downstream targets, probably still benefiting from ER-targeting agents. The lower ER expression in the other subgroup might be partially explained by ER activity still being blocked by recently administered endocrine treatment, indicating that biopsy timing relative to endocrine treatment needs to be considered when interpreting transcriptomic data.
Journal • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • FGFR1 (Fibroblast growth factor receptor 1) • NF1 (Neurofibromin 1) • TSPYL1 (Testis-Specific Y-Encoded-Like Protein 1)
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HER-2 positive • ER positive • HER-2 negative • FGFR1 amplification • ER mutation • ER negative • ESR1 mutation • ER positive + HER-2 negative
7ms
Acute myeloid leukemia with LRRFIP1::FGFR1 rearrangement and a complex karyotype. (PubMed, Cancer Genet)
NGS Archer FusionPlex (RNA) confirmed the LRRFIP1::FGFR1 rearrangement. This is the second reported case of AML with LRRFIP1::FGFR1 rearrangement and the first with a complex karyotype.
Journal
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FGFR1 (Fibroblast growth factor receptor 1) • RUNX1 (RUNX Family Transcription Factor 1) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • LRRFIP1 (LRR Binding FLII Interacting Protein 1)
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FGFR1 amplification • RUNX1 mutation • FGFR1 fusion • Chr del(5q) • FGFR1 rearrangement
8ms
FGF/FGFR1 system in paired breast tumor-adjacent and tumor tissues, associations with mammographic breast density and tumor characteristics. (PubMed, Front Oncol)
While no clear association between FGFR1 expression and MBD was found, FGF ligand (FGF1, FGF11, FGF18) expression was positively correlated with MBD. Taken together, these findings support a role of the FGF/FGFR1 system in early breast cancer which warrants further investigation in the MBD-breast cancer context.
Journal
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FGFR1 (Fibroblast growth factor receptor 1) • FGF18 (Fibroblast Growth Factor 18)
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FGFR1 amplification • FGFR1 expression
8ms
Efforts to Grow Genomic Research in Ancestrally Diverse and Admixed Populations. (PubMed, Cancer Res)
This study highlights the potential for inclusion of participants from diverse populations to accelerate discoveries and advance equity in genomic medicine, as well as the need for even larger collaborative initiatives. See related article by Ding et al., p. 2600.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • RUNX1 (RUNX Family Transcription Factor 1) • CCND1 (Cyclin D1) • CDH1 (Cadherin 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • GATA3 (GATA binding protein 3)
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TP53 mutation • PIK3CA mutation • PTEN mutation • FGFR1 amplification
8ms
Profiling the somatic mutational landscape of breast tumors from Hispanic/Latina women reveals conserved and unique characteristics. (PubMed, Cancer Res)
In conclusion, this study identified a higher prevalence of COSMIC signature 16 and a recurrent copy number amplification affecting expression of KIAA0100 in breast tumors from H/L compared to White women. These results highlight the necessity of studying under-represented populations.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • RUNX1 (RUNX Family Transcription Factor 1) • CCND1 (Cyclin D1) • CDH1 (Cadherin 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • GATA3 (GATA binding protein 3)
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TP53 mutation • HER-2 amplification • PIK3CA mutation • PTEN mutation • FGFR1 amplification
8ms
Target therapy matched to genomic alterations in patients with recurrent IDH wildtype glioblastoma: A real-life cohort analysis from Veneto Institute of Oncology, Padua (Italy) (ESMO 2023)
All pts received radiotherapy and temozolomide as first-line...TT was dabrafenib/trametinib (9 pts), larotrectinib (2 pts), erdafitinib (4 pts), entrectinib (1 pt), vebreltinib (2 pts), capmatinib (1 pt), alpelisib (6 pts), ipatasertib+/-atezolizumab (12 pts)...We had a dramatic response to a MET inhibitor. Deeper explorations are needed in targeting FGFR e ROS1.
Clinical • PD(L)-1 Biomarker
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • NTRK (Neurotrophic receptor tyrosine kinase) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1)
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BRAF V600E • PIK3CA mutation • BRAF V600 • MET amplification • FGFR1 amplification • ROS1 fusion • FGFR1 fusion • IDH wild-type • PIK3CA mutation + PTEN mutation • MET fusion • NTRK fusion
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Mekinist (trametinib) • Tecentriq (atezolizumab) • Tafinlar (dabrafenib) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • temozolomide • Piqray (alpelisib) • Balversa (erdafitinib) • ipatasertib (RG7440) • Tabrecta (capmatinib) • bozitinib (APL-101)
8ms
Mechanisms of Acquired Resistance to ALK Inhibitors Using Plasma Sequencing - Preliminary Data from the ATORG004 Study (IASLC-WCLC 2023)
In Cohort 1 (n=21), 15 (71%) pts had progressed on alectinib, 5 (24%) on ceritinib and 1 (5%) on ensartinib. In Cohort 2 (n=18), pts had progressed on crizotinib followed by alectinib (n=9, 50%), ceritinib (n=4, 22%) or brigatinib (n=3, 17%); 2 (11%) pts progressed on crizotinib, then ceritinib followed by alectinib...Of 5 pts with ALK resistance mutations (I1171N, V1180L, L1196M, G1202R, and E1210K) who subsequently received lorlatinib, repeat ctDNA NGS after 2 months demonstrated clearance of ALK resistance mutation(s) in 4/5 (80%) pts (i.e. undetectable on repeat testing)... Resistance mechanisms to ALK inhibitors are heterogenous, including both ALK dependent and independent pathways. DDR and cell cycle gene alterations were commonly detected and may represent previously unreported acquired resistance alterations. Comprehensive ctDNA NGS analysis at progression may help detect novel resistance alterations in patients on ALK inhibitors.
Preclinical • BRCA Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • EML4 (EMAP Like 4) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • KIF5B (Kinesin Family Member 5B) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • CDK4 (Cyclin-dependent kinase 4) • CDK12 (Cyclin dependent kinase 12) • CDK6 (Cyclin-dependent kinase 6)
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TP53 mutation • HER-2 amplification • NRAS mutation • HER-2 mutation • MET amplification • ALK rearrangement • FGFR1 amplification • ALK fusion • CDK12 mutation • ALK G1202R • ALK I1171N • EML4-ALK L1196M • ALK I1171 • ALK L1196M • ALK amplification • ALK E1210K • ALK V1180L • EML4-ALK G1202R
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Guardant360® CDx
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Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib) • Ensacove (ensartinib)
8ms
Study on the Molecular Markers of Resistance in the First-line Treatment of NSCLC with EGFR Positive by Aumolertinib (IASLC-WCLC 2023)
Based on NGS and PD-L1 IHC, gene mutation, TMB and PD-L1 expression are analyzed. Cox single factor and PFS are used to verify that these molecular markers are independent of TMB and PD-L1 for targeted therapy of lung cancer.
Clinical • PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)
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PD-L1 expression • EGFR mutation • BRAF mutation • PIK3CA mutation • MET amplification • EGFR T790M • PTEN mutation • FGFR1 amplification • CDKN2A mutation • PIK3CA amplification • EGFR positive • EGFR mutation + PIK3CA mutation • PIK3CA mutation + PTEN mutation • EGFR mutation + PTEN mutation • BRAF amplification
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Ameile (aumolertinib)
9ms
FOENIX-MBC2 TAS-120-201: A Study of TAS-120 in Patients With Metastatic Breast Cancer (clinicaltrials.gov)
P2, N=168, Active, not recruiting, Taiho Oncology, Inc. | Trial completion date: Jun 2023 --> Jul 2024
Trial completion date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • FGFR2 (Fibroblast growth factor receptor 2)
|
HER-2 amplification • HER-2 negative • FGFR1 amplification • FGFR2 amplification
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fulvestrant • Lytgobi (futibatinib)
9ms
Detection of Nine Oncogenes Amplification in Lung and Colorectal Cancer Formalin-Fixed Paraffin-Embedded Tissue Samples using Combined Next-Generation Sequencing-Based Script and Digital Droplet Polymerase Chain Reaction. (PubMed, Cancer Control)
Combined NGS-based script and ddPCR method is reliable and easily feasible for the detection of gene amplifications, providing useful data for guided therapy in cancer.
Retrospective data • Journal • Next-generation sequencing • Polymerase Chain Reaction
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1)
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HER-2 amplification • MET amplification • FGFR1 amplification • BRAF amplification
10ms
Driver and actionable mutations in younger patients with lung cancer - are we searching properly? (PubMed, Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub)
We detected very frequent driver and potentially actionable alterations in young patients with lung cancer. This suggests different mechanisms of carcinogenesis in these patients and indicates that they might benefit more from a specific approach than older lung cancer patients.
Journal
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR1 (Fibroblast growth factor receptor 1) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2)
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HER-2 amplification • MET amplification • FGFR1 amplification
11ms
Genomic profiling of biliary tract carcinomas by their location. (ASCO 2023)
Comprehensive genomic profiling of biliary tract cancers identifies numerous targetable alterations. The distribution of altered genes varies, suggesting that appropriate therapies may differ by location, reflecting different lineage types. >
Tumor mutational burden • BRCA Biomarker • IO biomarker
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • ARID2 (AT-Rich Interaction Domain 2)
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BRAF V600E • BRCA2 mutation • BRCA1 mutation • TMB-H • BRAF V600 • FGFR1 amplification • FGFR2 mutation • FGFR2 fusion
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OncoExTra™ test
11ms
Potential therapeutic implications of next generation sequencing (NGS)-based molecular profiling in HR+/HER2- metastatic breast cancer (mBC). (ASCO 2023)
PIK3CA is among the most frequently mutated genes in BC (approximately 40% of cases) and its mutations portend sensitivity to PI3K inhibitors, such as alpelisib, in combination with hormonal treatment in HR+/HER2- cases... In our analysis PIK3CA was confirmed to be the most frequently mutated gene (51% of cases); however, due to the specific European regulatory constraints, it was deemed to be actionable in a minority of cases, suggesting that NGS profiling should be performed early on after the diagnosis of metastatic disease, in order to inform the overall therapeutic strategy. Other potentially actionable alterations (FGFR1/2, AKT, HER2 ex 20 mutations) emerged from extended NGS profiling, suggesting its potential utility in selected HR+/HER2- mBC pts.
Tumor mutational burden • BRCA Biomarker • Next-generation sequencing • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • FGFR1 (Fibroblast growth factor receptor 1) • CCND1 (Cyclin D1) • PALB2 (Partner and localizer of BRCA2) • CDH1 (Cadherin 1) • NSD3 (Nuclear Receptor Binding SET Domain Protein 3) • RAD21 (RAD21 Cohesin Complex Component)
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HER-2 negative • PIK3CA mutation • HER-2 mutation • PIK3CA H1047R • FGFR1 amplification • PALB2 mutation • PIK3CA E545K • CCND1 amplification • PIK3CA E542K • PIK3CA E545 • PIK3CA E542 • PIK3CA N345K
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FoundationOne® CDx • TruSight Oncology 500 Assay
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Piqray (alpelisib)
11ms
Trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with HER2-low, hormone receptor-positive (HR+) unresectable and/or metastatic breast cancer (mBC): Exploratory biomarker analysis of DESTINY-Breast04. (ASCO 2023)
Greater clinical benefit was consistently observed with T-DXd vs TPC independent of intrinsic subtype, ESR1 mutation, PIK3CA mutation, or known CDK4/6i resistance marker status. Clinical trial information: NCT03734029. >aIncluded only pts with prior CDK4/6i and ≥1 gene alternation (CCND1, CCNE1, CDK6, FGFR1/2 amplification; RB1, PTEN, RAS, AKT1, ERBB2, FAT1 mutation).
Clinical • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • FAT1 (FAT atypical cadherin 1)
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HR positive • HER-2 amplification • PIK3CA mutation • PTEN mutation • FGFR1 amplification • FGFR2 amplification • ER mutation • ESR1 mutation • FAT1 mutation • PIK3CA mutation + ESR1 mutation • CDK4 mutation
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GuardantOMNI • Prosigna™ Breast Cancer Prognostic Gene Signature Assay
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Enhertu (fam-trastuzumab deruxtecan-nxki)
11ms
ESR1 mutational landscape and impact of co-existing resistance variants on clinical outcomes in patients with metastatic breast cancer. (ASCO 2023)
Recently, elacestrant, an oral SERD, was approved for patients with HR+/HER2- ESR1mutmetastatic breast cancer (MBC)...Among a clinically annotated HR+/HER2- subgroup (n = 350), 51 patients received SERD monotherapy, either fulvestrant (n = 9) or oral SERD on clinical trial (n = 42); among 28 patients with cfDNA variants associated with SERD resistance, median PFS and OS were lower compared to the 23 patients without resistance mutations (PFS: 2.4 vs 11.3 mo; HR = 0.44; 95% CI, 0.23-0.81; p = 0.008; and OS: 21.1 vs 31.4 mo; HR 0.47; 95% CI, 0.22-0.98; p = 0.045). ESR1 mutations that qualify patients to receive approved SERD therapy are detectable by plasma-based genotyping and can associate with various genomic co-alterations, including variants that may impact clinical outcomes. Further research is needed to confirm the impact of co-alterations in additional datasets and evaluate the role of SERD-based combination therapy to further improve clinical outcomes of patients with MBC.
Clinical data • Clinical • Metastases
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
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HER-2 negative • HER-2 mutation • FGFR1 amplification • ER mutation • ESR1 mutation
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Guardant360® CDx
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fulvestrant • Orserdu (elacestrant)
11ms
Genomic characterization of FGFR-altered solid tumors using a clinically annotated pan-cancer repository. (ASCO 2023)
Activating FGFR fusions, which occur across tumor types with marked diversity in fusion partners, present opportunities for future drug development. Non-target FGFR alterations in iCCA and UC, particularly those that cluster with target FGFR alterations, may be candidates for future FGFR-targeted strategies.
Clinical • Pan tumor
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TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • ARID1A (AT-rich interaction domain 1A) • FGFR (Fibroblast Growth Factor Receptor) • TACC3 (Transforming acidic coiled-coil containing protein 3) • BAP1 (BRCA1 Associated Protein 1)
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FGFR1 amplification • FGFR2 mutation • FGFR2 fusion • FGFR3 mutation • FGFR fusion • FGFR1 fusion • FGFR3 amplification
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MSK-IMPACT
12ms
Clinical Genetic Features and Neoadjuvant Chemotherapy Response in HER2-Low Breast Cancers: A Retrospective, Multicenter Cohort Study. (PubMed, Ann Surg Oncol)
HER2-low breast cancers have significant genetic differences from HER2-positive cases. Genetic heterogeneity exists in HER2-low breast cancers and impacts on NAC response in this subgroup.
Retrospective data • Journal
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • FGFR1 (Fibroblast growth factor receptor 1) • TOP2A (DNA topoisomerase 2-alpha) • MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4)
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HER-2 positive • TP53 mutation • HER-2 amplification • HER-2 mutation • FGFR1 amplification • ER mutation • ESR1 mutation • ER amplification
1year
FOENIX-MBC2 TAS-120-201: A Study of TAS-120 in Patients With Metastatic Breast Cancer (clinicaltrials.gov)
P2, N=168, Active, not recruiting, Taiho Oncology, Inc. | Recruiting --> Active, not recruiting
Enrollment closed • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • FGFR2 (Fibroblast growth factor receptor 2)
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HER-2 amplification • HER-2 negative • FGFR1 amplification • FGFR2 amplification
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fulvestrant • Lytgobi (futibatinib)
1year
Long term results and ctDNA correlatives for CAPOX BETR: A multi-center phase II trial of capecitabine, oxaliplatin, bevacizumab and trastuzumab for previously untreated HER2 positive metastatic gastroesophageal adenocarcinoma (AACR 2023)
"The combination of CAPOX, trastuzumab and bevacizumab shows striking clinical activity comparable to novel triplet regimens that include PD1 blockade for HER2+ GEAs . Further evaluation of VEGF mAb in combination with chemoimmunotherapy and anti-PD1 regimens is warranted. Diagnostic ctDNA profiling identifies cases with high TF and alternative MAPK drivers who have worse outcomes."
P2 data • Clinical • Circulating tumor DNA
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1)
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HER-2 positive • KRAS mutation • BRAF mutation • HER-2 amplification • NRAS mutation • MET amplification • PTEN mutation • FGFR1 amplification
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PredicineCARE™
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Avastin (bevacizumab) • Herceptin (trastuzumab) • capecitabine • oxaliplatin
1year
Targeted down regulation of FGFR1 through G-quadruplex stabilization in metastatic breast cancer (AACR 2023)
Importantly, use of the G4-binding compound CX-5461 stabilized the FGFR1 G4 structure, blocked the transcriptional activity of the FGFR1 proximal promoter and decreased FGFR1 expression...In conclusion, our evaluation of FGFR kinase inhibitors validates clinically observed resistance to this approach in MBC. Moreover, our findings suggest that G4 stabilization may be a potential therapeutic strategy for FGFR1 expressing MBC.
Metastases
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FGFR1 (Fibroblast growth factor receptor 1)
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FGFR1 amplification • FGFR1 expression
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pidnarulex (CX-5461)