News - HER-2 amplification + PD-L1 expression

13d

Comprehensive liquid biopsy analysis for monitoring NSCLC patients under second-line osimertinib treatment. (PubMed, Front Oncol)

AXL and PIM-1 expression detected in CTCs during treatment suggesting new possible therapeutic strategies. Our results reveal that comprehensive liquid biopsy analysis can efficiently represent the heterogeneous molecular landscape and provide prominent information on subsequent treatments for NSCLC patients at PD since druggable molecular alterations were detected in CTCs.

13 days ago

Journal • Liquid biopsy • PD(L)-1 Biomarker • IO biomarker • Biopsy

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) • AXL (AXL Receptor Tyrosine Kinase) • B2M (Beta-2-microglobulin) • FOXA1 (Forkhead Box A1) • PIM1 (Pim-1 Proto-Oncogene) • VIM (Vimentin) • ALDH1A1 (Aldehyde Dehydrogenase 1 Family Member A1) • KRT19 (Keratin 19) • RASSF1 (Ras Association Domain Family Member 1) • WIF1 (WNT Inhibitory Factor 1) • BRMS1 (BRMS1 Transcriptional Repressor And Anoikis Regulator)

PD-L1 expression • BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • HER-2 amplification • PIK3CA mutation • BRAF V600 • MET amplification • EGFR T790M • MET mutation • KRAS G12 • EGFR mutation + PIK3CA mutation • HER-2 amplification + PD-L1 expression • VIM expression • HER-2 amplification + MET amplification • RASSF1 methylation

Tagrisso (osimertinib)

19d

Disitamab vedotin combined with apatinib in gastric cancer: A case report and review of literature. (PubMed, World J Clin Oncol)

Despite the unfavorable prognosis associated with advanced GC, the implementation of personalized treatment approaches may still prove beneficial for select patients. In patients with HER2-positive GC with extensive metastatic involvement, the use of the HER2-targeted combination with apatinib has demonstrated the potential to prolong both PFS and overall survival.

19 days ago

Review • Journal • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)

PD-L1 expression • HER-2 positive • MSI-H/dMMR • HER-2 overexpression • HER-2 amplification • HER-2 amplification + PD-L1 expression • HER-2 positive + HER-2 overexpression

Opdivo (nivolumab) • Herceptin (trastuzumab) • AiTan (rivoceranib) • Aidixi (disitamab vedotin) • anbenitamab (KN026)

Immunological responses to brain metastasis stereotactic radiosurgery in patient-matched longitudinal blood and tumour samples. (PubMed, Clin Transl Radiat Oncol)

A sizeable proportion of T cell clonotypes were retained post-SRS, and four clones demonstrated significant, non-stochastic expansion. Systemic and local immunological changes in this homogenous patient cohort suggest that SRS may facilitate MHC-II-restricted T cell priming responses involving the monocyte-macrophage lineage and CD4+ T cells, which should be further explored.

1 month ago

Journal • PD(L)-1 Biomarker • IO biomarker • Surgery

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD4 (CD4 Molecule)

PD-L1 expression • HER-2 amplification • PD-1 expression • HER-2 amplification + PD-L1 expression • MHC-II expression • CD4 expression

HER2 amplification and PD-L1 expression in invasive stratified mucin-producing carcinoma of the cervix: a clinicopathological analysis of eighteen cases (PubMed, Zhonghua Bing Li Xue Za Zhi)

PD-L1 is positive in most of the ISMC cases, while HER2 is amplified or lowly expressed in a small portion of them. Thus, it is possible to treat ISMC patients with therapies targeting PD-L1 and therapy targeting HER2.

1 month ago

Retrospective data • Journal • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)

PD-L1 expression • HER-2 amplification • HER-2 expression • PD-L1 amplification • HER-2 amplification + PD-L1 expression • PD-L1 expression + HER-2 overexpression

6ms

Molecular landscape and clinical implication of CCNE1-amplified esophagogastric cancer. (PubMed, Cancer Res Commun)

Real-world survival analysis demonstrated that patients with CCNE1-amplified gastric cancer had worse survival after trastuzumab for HER2-positive tumors, but better survival after immunotherapy. These data suggest that CCNE1-amplified gastric cancer has a distinct molecular and immune profile with important therapeutic implications, and therefore further investigation of CCNE1 amplification as a predictive biomarker is warranted.

6 months ago

Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • CCNE1 (Cyclin E1) • CDH1 (Cadherin 1)

PD-L1 expression • HER-2 positive • TP53 mutation • HER-2 amplification • HER-2 mutation • CCNE1 amplification • CCNE1 overexpression • CDH1 mutation • HER-2 amplification + PD-L1 expression

Herceptin (trastuzumab)

7ms

Agnostic Administration of Targeted Anticancer Drugs: Looking for a Balance between Hype and Caution. (PubMed, Int J Mol Sci)

Several agnostic drug-target matches have already been approved for clinical use, e.g., immune therapy for tumors with microsatellite instability (MSI) and/or high tumor mutation burden (TMB), NTRK1-3 and RET inhibitors for cancers carrying rearrangements in these kinases, and dabrafenib plus trametinib for BRAF V600E mutated malignancies. The existing format of data dissemination may not be optimal for agnostic cancer medicine, as conventional scientific journals are understandably biased towards the publication of positive findings and usually discourage the submission of case reports. Despite all the limitations and concerns, histology-independent drug-target matching is certainly feasible and, therefore, will be increasingly utilized in the future.

7 months ago

Review • Journal • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • HRD (Homologous Recombination Deficiency)

PD-L1 expression • BRAF V600E • TMB-H • HER-2 overexpression • HER-2 amplification • BRAF V600 • HRD • RET mutation • ALK translocation • NTRK1 mutation • HER-2 amplification + PD-L1 expression

Mekinist (trametinib) • Tafinlar (dabrafenib)

7ms

Human epidermal growth factor receptor-2 expression and subsequent dynamic changes in patients with ovarian cancer. (PubMed, Sci Rep)

Patients with HER2-overexpressing OC exhibited distinct histological, IHC, and genomic profiles. HER2-targeting agents are potential options for BRCA-wildtype patients, particularly as later lines of treatment.

7 months ago

Journal • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker

PD-L1 expression • TP53 mutation • KRAS mutation • HER-2 overexpression • HER-2 amplification • PIK3CA mutation • PD-L1 underexpression • ARID1A mutation • BRCA wild-type • TP53 expression • BRCA mutation • HER-2 amplification + PD-L1 expression • PD-L1-L

8ms

Frequency and Nature of Genomic Alterations in ERBB2-Altered Urothelial Bladder Cancer. (PubMed, Target Oncol)

We noted important differences in co-occurring GA in ERBB2-altered (ECDmut+, KDmut+, amp+) versus ERBB2wt UBC, as well as higher mean TMB and higher APOBEC mutational signature in the ERBB2-altered groups. Our results can help refine future clinical trial designs and elucidate possible response and resistance mechanisms for ERBB2-altered UBC.

8 months ago

Journal • Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • MTAP (Methylthioadenosine Phosphorylase) • TOP2A (DNA topoisomerase 2-alpha) • APOB (Apolipoprotein B)

PD-L1 expression • MSI-H/dMMR • HER-2 overexpression • HER-2 amplification • HER-2 mutation • HER-2 amplification + PD-L1 expression

PD-L1 IHC 22C3 pharmDx

8ms

COMPARISON OF EPSTEIN BARR VIRUS POSITIVITY, MICROSATELLITE INSTABILITY, HER2 AMPLIFICATION, AND PD-L1 EXPRESSION IN GASTRIC CARCINOMAS WITH LYMPHOID STROMA AND CONVENTIONAL GASTRIC ADENOCARCINOMAS (DDW 2024)

EBV positivity larger tumor size high T and N categories and advanced AJCC stage were significantly associated with PD-L1 positivity in GCLSs. Conclusions : Patients with GCLS have shown high rates of EBV infection MSI-H and high PD-L1 positivity but a low rate of HER amplification rendering them promising candidates for anti-PD-1 therapy but less likely for anti-HER drug.

8 months ago

Microsatellite instability • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker • Stroma

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)

PD-L1 expression • MSI-H/dMMR • HER-2 amplification • HER-2 amplification + PD-L1 expression

VENTANA PD-L1 (SP263) Assay

10ms

Histologic Subtypes And Immune Markers Of HER2-Amplified Cervical Cancer (ESGO 2024)

Among patients expressing 2+ or 3+ HER2 and treated with the HER2-targeting agent, those treated with T-DXd displayed prolonged progression-free survival (PFS) after treatment, with a median of 17.5 months (n=4). Conversely, two patients treated with Trastuzumab emtansine (T-DM1) experienced a poor prognosis, with a median PFS of one month...These subtypes are known to be associated with a poor prognosis with conventional therapy, making them potentially suitable targets for high-efficacy treatments. Further studies are required to confirm the efficacy in HER2-amplified cervical cancer.

10 months ago

PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)

PD-L1 expression • HER-2 amplification • HER-2 expression • HER-2 amplification + PD-L1 expression

PD-L1 IHC 22C3 pharmDx

Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki)

11ms

HER2 and PD-L1 immunohistochemistry (IHC) expression, and HER2 genomic alterations: Associations and clinical outcomes for advanced bladder cancer. (ASCO-GU 2024)

Our study is the first to describe an inverse correlation between HER2 IHC expression and PD-L1 CPS score. Furthermore, HER2 IHC overexpression is strongly associated with HER2 amplification, but a subset of patients with high HER2 protein expression are potentially missed by genomic profiling alone. HER2 expression by IHC or HER2 genomic alteration is not a prognostic marker for MIBC pts in this cohort.

11 months ago

Clinical data • Clinical • PD(L)-1 Biomarker • IO biomarker • Metastases

HER-2 (Human epidermal growth factor receptor 2)

PD-L1 expression • HER-2 overexpression • HER-2 amplification • HER-2 expression • HER-2 amplification + PD-L1 expression

MSK-IMPACT

12ms

The genomic and immune landscapes of gastric cancer and their correlations with HER2 amplification and PD-L1 expression. (PubMed, Cancer Med)

The combination of HER2 amplification and PD-L1 expression in Chinese patients with GC could stratify the total populations into several subgroups with distinctive genomic and immune landscapes, which should be considered when making personalized treatment decisions.

12 months ago

Journal • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • KMT2D (Lysine Methyltransferase 2D) • CDH1 (Cadherin 1)

PD-L1 expression • TP53 mutation • KRAS mutation • TMB-H • MSI-H/dMMR • HER-2 overexpression • HER-2 amplification • PIK3CA mutation • HER-2 expression • ARID1A mutation • MYC amplification • PD-L1 amplification • HER-2 amplification + PD-L1 expression • CCNE1 mutation

1year

Genetic landscape and PD-L1 expression in Epstein-Barr virus-associated gastric cancer according to the histological pattern. (PubMed, Sci Rep)

Moreover, the histological pattern of EBVaGCs was significantly associated with the levels of TILs (P = 0.005) and combined positive score (P = 0.027). In conclusion, patients with EBVaGCs with different histological patterns exhibited distinct genetic alteration, PD-L1 expression, and degree of TILs.

1 year ago

Journal • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • CDH1 (Cadherin 1) • MUC6 (Mucin 6)

PD-L1 expression • TP53 mutation • HER-2 amplification • PIK3CA mutation • CDH1 mutation • HER-2 amplification + PD-L1 expression

1year

TRUDI: A phase II study of neoadjuvant TRastuzumab derUxtecan and Durvalumab for stage III HER2-expressing Inflammatory breast cancer (SABCS 2023)

Exploratory objectives will investigate biomarker analyses on tissue, blood, and microbiome to explore the association of HER2 expression, immune variables, and stool composition on the efficacy of T-DXd with durvalumab among patient with HER2-expressing IBC. To our knowledge, this is the first and only ongoing study testing the combination of an anti-HER2 antibody-drug conjugate with immunotherapy for the neoadjuvant treatment of patients with IBC.

1 year ago

Clinical • P2 data • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)

PD-L1 expression • HER-2 positive • HER-2 expression • HER-2 amplification + PD-L1 expression

Imfinzi (durvalumab) • Enhertu (fam-trastuzumab deruxtecan-nxki)

over1year

Frequency and nature of genomic alterations (GA) in ERBB2-altered urothelial bladder cancer (UBC) (ESMO 2023)

Table: 2400P Conclusions We noted important differences in co-occurrent-GA in ERBB2-altered (ECDmut, KDmut, amp) vs wt UBC, and higher mean TMB and higher APOBEC mut signature in the ERBB2-altered group. Results can help refine future clinical trial designs and help elucidate possible resistance mechanisms for ERBB2-altered UBC.

over 1 year ago

Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker

PD-L1 expression • MSI-H/dMMR • HER-2 overexpression • HER-2 amplification • HER-2 mutation • HER-2 amplification + PD-L1 expression

PD-L1 IHC 22C3 pharmDx

over1year

Micropapillary histology (MPUC) and extra-cellular domain ERBB2 (ERBB2 ECD+) mutations in urothelial bladder cancer (UBC) (ESMO 2023)

Background Given the early promising data with afatinib in advanced UC and the recent approval in NSCLC for anti-HER2 targeted therapy for activating kinase domain exon 20 ERBB2 insertion mutations, there is considerable interest in targeting additional locations in the ERBB2 gene in other tumor types...Conclusions ERBB2 ECD mutation-driven UBC represents a distinct subtype of UBC featuring an enrichment of MPUC histology from 1-2% to 28% incidence in ERBB2 ECD mutated UBC, and unique clinical and molecular characteristics, including differences in mutational signatures and genetic ancestry. Further exploration of anti-HER2 targeted therapy for non-amp sequence mutations in ERBB2 in UBC appears warranted.

over 1 year ago

Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • RB1 (RB Transcriptional Corepressor 1) • MTAP (Methylthioadenosine Phosphorylase) • KMT2D (Lysine Methyltransferase 2D)

PD-L1 expression • MSI-H/dMMR • PD-L1 overexpression • HER-2 amplification • HER-2 mutation • HER-2 S310F • HER-2 S310Y • HER-2 exon 20 mutation • HER-2 amplification + PD-L1 expression • PD-L1 expression + MSI-H/dMMR

PD-L1 IHC 22C3 pharmDx

Gilotrif (afatinib)

over1year

Demographic and Genomic Characteristics of Non-Small Cell Lung Cancer Patients with ARID1A Alterations (IASLC-WCLC 2023)

This case-control study provides a mutational landscape and demographic profile for NSCLC patients with ARID1A alts. Notably our data support the finding that EGFR mutations are less prevalent in patients with ARID1A alt, which is relevant as ICI efficacy is low in patients with EGFR mutated NSCLC. The efficacy of ICI in our cases and controls is being analyzed to shed light on whether ARID1A alts warrant further evaluation as a biomarker for ICI efficacy.

over 1 year ago

Clinical • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • STK11 (Serine/threonine kinase 11) • ARID1A (AT-rich interaction domain 1A) • KEAP1 (Kelch Like ECH Associated Protein 1)

PD-L1 expression • TP53 mutation • BRAF V600E • KRAS mutation • EGFR mutation • TMB-H • PD-L1 overexpression • KRAS G12C • HER-2 overexpression • HER-2 amplification • BRAF V600 • MET amplification • ARID1A mutation • MET exon 14 mutation • RET mutation • KEAP1 mutation • MET mutation • KRAS G12 • HER-2 amplification + PD-L1 expression

Guardant360® CDx

over1year

Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Pleomorphic Lobular Breast Carcinoma. (PubMed, Cancers (Basel))

This study shows that pILCs show some degree of sTILs and PD-L1 expression; however, this was not associated with a survival improvement. Additional large trials are needed to understand immune infiltration in lobular cancer, especially in the pleomorphic subtype.

over 1 year ago

Journal • Tumor-infiltrating lymphocyte • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • PD-1 (Programmed cell death 1) • NODAL (Nodal Growth Differentiation Factor)

PD-L1 expression • HR positive • HER-2 amplification • PD-1 expression • ER expression • HER-2 amplification + PD-L1 expression • ER amplification

PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP142) Assay

over1year

Urothelial Bladder Cancer: Genomic Alterations in Fibroblast Growth Factor Receptor. (PubMed, Mol Diagn Ther)

An increased frequency of genomic alterations is observed in UBC FGFR. These have been linked to immune checkpoint inhibitor resistance. Clinical trials are needed to evaluate UBC FGFR-based biomarkers prognostic of an immune checkpoint inhibitor response. Only then can we successfully incorporate novel therapeutic strategies into the evolving landscape of UBC treatment.

over 1 year ago

Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • FGFR (Fibroblast Growth Factor Receptor) • MTAP (Methylthioadenosine Phosphorylase) • FGFR4 (Fibroblast growth factor receptor 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

PD-L1 expression • HER-2 amplification • TMB-L • FGFR1 fusion • FGFR3 fusion • HER-2 amplification + PD-L1 expression

PD-L1 IHC 22C3 pharmDx

over1year

Somatic mutation profiling, tumor-infiltrating leukocytes, tertiary lymphoid structures and PD-L1 protein expression in HER2-amplified colorectal cancer. (PubMed, PeerJ)

However, none of them were associated with the prognosis of HACC. In all, HER2 amplification is correlated with distant metastasis and TP53 gene mutation may be a potential protective mechanism of HACC.

over 1 year ago

Journal • PD(L)-1 Biomarker • IO biomarker • Tumor-infiltrating-leukocyte

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53)

PD-L1 expression • HER-2 positive • TP53 mutation • PD-L1 overexpression • HER-2 amplification • HER-2 negative • HER-2 expression • HER-2 amplification + PD-L1 expression

over1year

RNA sequencing as a confirmatory assay and its impact on patient care in multiple cancer types. (ASCO 2023)

In order to target HER2, systemic treatment was changed to a combination containing trastuzumab and pertuzumab, resulting in pathological complete response...Staining showed high PDL-1 (CPS50), prompting a change in therapy to an anti-PDL-1 (pembrolizumab) therapy... RNA-seq is emerging as an objective tool to evaluate key diagnostic and targetable events in multiple cancer types. The use of RNA-seq can also add value as an objective measurement to confirm critical IHC findings, potentially changing clinical care.

over 1 year ago

Clinical • PD(L)-1 Biomarker • IO biomarker

TNFRSF8 (TNF Receptor Superfamily Member 8)

PD-L1 expression • HER-2 positive • PD-L1 overexpression • HER-2 negative • HER-2 expression • TNFRSF8 positive • TNFRSF8 expression • HER-2 amplification + PD-L1 expression • TNFRSF8 negative • TNFRSF8 overexpression

Prosigna™ Breast Cancer Prognostic Gene Signature Assay • BostonGene Tumor Portrait™ Test

Keytruda (pembrolizumab) • Herceptin (trastuzumab) • Perjeta (pertuzumab)

over1year

The heterogeneous immune and molecular landscape of endometrial cancer metastases (AACR 2023)

ECM to GU (n=29, HR: 1.59, 570 days, p=0.04) had worse post-Carboplatin survival than ECP (n=3023, 1096 days) while ECM to Lung had better (n=279, HR: 0.73, 1602 days, p=<0.01). ECM to Liver (PD-1/PD-L1i: n=27, HR: 2.4, 165 days, p=<0.01; Bevacizumab: n=44, HR: 1.5, 286 days, p=0.03) had worse post-tx survival compared to ECP (PD-1/PD-L1i: n=607, 760 days; Bevacizumab: n=693, 463 days). ECM to Bone and GU organs have unique molecular alterations when compared to ECP of the uterus and have lower infiltration of immune cells. We also highlight differences in OS when comparing different ECM.

over 1 year ago

Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PGR (Progesterone receptor) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • ARID1A (AT-rich interaction domain 1A) • PD-1 (Programmed cell death 1) • ASXL1 (ASXL Transcriptional Regulator 1) • FGF19 (Fibroblast growth factor 19) • KMT2D (Lysine Methyltransferase 2D) • RNF43 (Ring Finger Protein 43) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • FGF3 (Fibroblast growth factor 3)

PD-L1 expression • TMB-H • MSI-H/dMMR • HER-2 amplification • HER-2 amplification + PD-L1 expression

VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™

Avastin (bevacizumab) • carboplatin • gemcitabine

over1year

Cancer of unknown Primary (CUP): Beyond the identification of the site of origin by an integrative genomic approach (AACR 2023)

Based on CUP tumor profiling by this platform, positive treatment response has been observed in 3 out of 4 CUP patients thus far, e.g., one patient with metastatic disease that showed high TMB and immune infiltrated microenvironment treated with Ipilimumab and Nivolumab had a sustained response. Therapy in oncology is often determined by the tissue origin, making CUP a therapeutic challenge. In this study, we demonstrate the application of an integrative WES and RNAseq platform to not only predict the site of origin, but also to identify relevant biomarkers and therapeutic targets in CUP.

over 1 year ago

Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • NF1 (Neurofibromin 1) • MSH2 (MutS Homolog 2) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • PD-L2 (Programmed Cell Death 1 Ligand 2) • FANCA (FA Complementation Group A) • NCOA4 (Nuclear Receptor Coactivator 4)

PD-L1 expression • TP53 mutation • KRAS mutation • BRCA1 mutation • TMB-H • HER-2 amplification • RET fusion • HRD • PTEN mutation • FGFR1 amplification • NF1 mutation • HRD + BRCA1 mutation • MSH2 mutation • FANCA mutation • NCOA4-RET fusion • ATM overexpression • HER-2 amplification + PD-L1 expression • ATM expression

Opdivo (nivolumab) • Yervoy (ipilimumab)

over1year

Assessment of HER2 in Gastric Type Endocervical Adenocarcinoma and its Prognostic Significance. (PubMed, Mod Pathol)

PD-L1 expression was associated with worse PFS (p=0.032), while mutant type p53 demonstrated no prognostic significance. Our work laid a solid foundation for the eventual development of a future standard HER testing guideline for GEAs.

over 1 year ago

Journal • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53)

PD-L1 expression • HER-2 positive • TP53 mutation • HER-2 overexpression • HER-2 amplification • HER-2 amplification + PD-L1 expression

almost2years

Biomarker Data From the Phase III KATHERINE Study of Adjuvant T-DM1 Versus Trastuzumab for Residual Invasive Disease After Neoadjuvant Therapy for HER2-Positive Breast Cancer. (PubMed, Clin Cancer Res)

T-DM1 appears to overcome HER2 resistance. T-DM1 benefit does not appear dependent on immune activation, but these results do not rule out an influence of the tumor immune microenvironment on degree of response.

almost 2 years ago

Journal • P3 data • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CD8 (cluster of differentiation 8)

PD-L1 expression • HER-2 positive • HER-2 amplification • PIK3CA mutation • HER-2 expression • PIK3CA amplification • CD8 expression • PIK3CA expression • HER-2 amplification + PD-L1 expression • PD-L1-L

Prosigna™ Breast Cancer Prognostic Gene Signature Assay

Kadcyla (ado-trastuzumab emtansine)

almost2years

Expression and correlation of PD-L1 and HER2 in oesophageal squamous cell carcinoma. (PubMed, J Clin Pathol)

PD-L1 expression was significantly positively correlated with HER2 expression in OSCC. The results provide valuable insight for the future application of HER2-targeted therapy combined with immunotherapy in OSCC.

almost 2 years ago

Journal • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)

PD-L1 expression • HER-2 amplification • HER-2 expression • HER-2 amplification + PD-L1 expression • PD-L1 expression + HER-2 overexpression

almost2years

Acquired EGFR Resistant Mutations and Co-mutations in Tumors Of Non-small Cell Lung Cancer Patients Treated With Tyrosine Kinase Inhibitors (TKI) (LALCA 2023)

"While T790M and C797S mutations are well described, we document L718V mutations in osimertinib-treated pts with an original L858R. We need to increase NGS in pts who develop resistance because it is very heterogeneous and will help to develop new TKIs."

almost 2 years ago

Clinical

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • MSI (Microsatellite instability) • SMAD4 (SMAD family member 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)

PD-L1 expression • TP53 mutation • EGFR mutation • TMB-H • MSI-H/dMMR • HER-2 amplification • PIK3CA mutation • EGFR L858R • MET amplification • EGFR T790M • EGFR C797S • EGFR T790M + EGFR C797S • HER-2 amplification + PD-L1 expression

PD-L1 IHC 22C3 pharmDx

Tagrisso (osimertinib)

almost2years

Characteristics of the immunogenicity and tumor immune microenvironment in HER2-amplified lung adenocarcinoma. (PubMed, Front Immunol)

Patients with HER2-amplified LUAD have better immunogenicity and/or an inflamed TIME among HER2-aberrant tumors. Our study may provide clues for establishing the benefits and uses of ICIs for patients with this disease.

almost 2 years ago

Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)

PD-L1 expression • HER-2 amplification • HER-2 expression • HER-2 amplification + PD-L1 expression

almost2years

KRAS Targetable Mutation Profile and PD-L1 Expression in Resected Mucinous Adenocarcinoma of the Lung (USCAP 2023)

While KRAS mutations are common in mucinous adenocarcinoma of the lung, sotorasib targetable p.G12C mutation is uncommon in this distinct subtype. The association of KRAS mutations with mucinous adenocarcinoma tumor size suggests earlier somatic mutations may exist to initiate its carcinogenesis. Absent or low PD-L1 expression on mucinous adenocarcinoma cells make it challenging for systemic immunotherapy for this distinct entity.

almost 2 years ago

PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

PD-L1 expression • KRAS mutation • EGFR mutation • KRAS G12C • BRAF mutation • HER-2 amplification • HER-2 mutation • MET amplification • MET mutation • KRAS G12 • HER-2 amplification + PD-L1 expression • PD-L1-L

VENTANA PD-L1 (SP142) Assay

Lumakras (sotorasib)

almost2years

Impact of oncogenic alterations on the effectiveness of chemotherapy combination - immunotherapy in non -epidermoid bronchial cancers non -small cells: study of a multicenter multicenter cohort (CPLF 2023)

Conclusion in our study, the effectiveness of the CT + combination here was unequal depending on the molecular profile but did not seem affected by the EGFR, ALK, Ros1 and Ret alterations. These results, which require being confirmed, could question the systematic exclusion of these patients of clinical trials evaluating CT + combinations here.

almost 2 years ago

Clinical • PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • STK11 (Serine/threonine kinase 11)

PD-L1 expression • TP53 mutation • KRAS mutation • EGFR mutation • BRAF mutation • HER-2 amplification • MET amplification • ALK rearrangement • MET exon 14 mutation • STK11 mutation • MET overexpression • RET mutation • MET mutation • RET rearrangement • HER-2 amplification + PD-L1 expression

almost2years

Molecular landscape and clinical implication of CCNE1-ampliﬁed esophagogastric cancer. (ASCO-GI 2023)

"While there were no differences in OS between CCNE1-amp vs non-amp GA, CCNE1Amp was associated with worse OS after trastuzumab in the IHC HER2+ cohort (N=9 vs 28; HR (95% CI): 2.95 (1.18 – 7.34), p = 0.015)...CCNE1Amp is associated with a distinct molecular profile in EGC and resistance to HER2-targeted therapy. While CCNE1-amp tumors are thought to be generally “immune-cold,”CCNE1-amp GA demonstrated potentially improved outcomes with immunotherapy. Further investigation of CCNE1Amp as a predictive biomarker is warranted, particularly as novel therapeutics selectively targeting CCNE1Amp are under clinical investigation."

almost 2 years ago

Clinical

PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CCNE1 (Cyclin E1) • CDH1 (Cadherin 1)

PD-L1 expression • HER-2 positive • MSI-H/dMMR • HER-2 amplification • HER-2 mutation • CCNE1 amplification • CDKN2A mutation • HER-2 amplification + PD-L1 expression • CCNE1 expression • PD-L1 expression + MSI-H/dMMR

PD-L1 IHC 22C3 pharmDx

Herceptin (trastuzumab)

2years

Goblet Cell Adenocarcinoma (GCA) of the Appendix: Interrogating Proteomics to Identify Potential Actionable Targets (NANETS 2022)

There were no statistically significant clinicopathologic differences between patients with HER2 2+/3+ and HER2 1+ tumors though patients with HER2 overamplified disease were more likely to recur compared to patients with HER2 unamplified disease (43% versus 0%, Chi-squared test p= .09).CONCLUSIONS For the first time we have demonstrated that HER-2 is overexpressed in a significant proportion of patients with GCAs, suggesting that this can be a potential therapeutic target to explore clinically. Furthermore, the absence of SSTR2 in GCAs suggests that the tumor is much more akin to an adenocarcinoma than low grade NET.

2 years ago

PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • CLDN18 (Claudin 18) • PD-1 (Programmed cell death 1) • SSTR (Somatostatin Receptor) • SSTR2 (Somatostatin Receptor 2)

PD-L1 expression • HER-2 overexpression • HER-2 amplification • PD-1 expression • HER-2 amplification + PD-L1 expression

2years

Genomic and Transcriptomic Landscape of HER2-Low Breast Cancer (SABCS 2022)

With some exceptions, H2L breast cancer shared genomic features with its more classically defined subset of either HR+ or HRneg disease. Notable differences in PIK3CA (an actionable mutation) and TP53 (a prognostic alteration) warrant additional assessment, as do amplifications variable between HR+H2L and HR+Her2pos groups. Our findings add tremendously to the current understanding of the molecular profile of the H2L subgroup and comparison to the classically defined breast cancer subgroups.

2 years ago

Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • RNF43 (Ring Finger Protein 43) • CDH1 (Cadherin 1) • FGF3 (Fibroblast growth factor 3) • FGF4 (Fibroblast growth factor 4) • NSD3 (Nuclear Receptor Binding SET Domain Protein 3) • CLTC (Clathrin Heavy Chain) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • DDX5 (DEAD-Box Helicase 5) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting)

PD-L1 expression • HER-2 positive • TP53 mutation • TMB-H • HR positive • HER-2 amplification • PIK3CA mutation • PTEN mutation • CCND1 amplification • HER-2 amplification + PD-L1 expression

VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™

2years

MODULATION OF FIRST-LINE COMBINATION IMMUNE CHECKPOINT INHIBITORS (ICIS) AND PLATINUM-BASED CHEMOTHERAPY IN NON-SMALL CELL LUNG CANCER (NSCLC) TREATMENT IN CLINICAL PRACTICE (AIOM 2022)

We evaluated safety, activity, efficacy of combined ICIs/ platinum-based chemotherapy in clinical practice. Clinical parameters, age, performance status (PS), comorbidities evaluated by Cumulative Illness Rating Scale (CIRS), distinguished patients in fit or unfit to conventional treatment, treated with standard doses/schedules, pembrolizumab 200 mg added to cisplatin (75 mg/mq) or carboplatin (AUC 5) plus pemetrexed (500 mg/mq) or carboplatin (AUC 5) plus paclitaxel (175 mg/mq), d1 every 3 weeks, or modulated doses/schedules, respectively. Most metastatic NSCLC patients suitable for first-line ICIs/platinum-based chemotherapy combinations were elderly, unfit for recommended doses and/or schedules. Proper treatment modulations were tolerable in unfit patients treated in clinical practice, and guarantee consistent activity and efficacy. Updated safety, activity, efficacy data will be presented.

2 years ago

Clinical • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

PD-L1 expression • MSI-H/dMMR • HER-2 amplification + PD-L1 expression

Keytruda (pembrolizumab) • cisplatin • carboplatin • paclitaxel • pemetrexed

2years

Prevalence and prognosis of ER-loss in advanced invasive lobular carcinoma (SABCS 2022)

In this large real-word dataset, ER-loss likely occurred in 11.4% of ILC and was associated with worse OS compared to both patients with IDC and ER-loss and ILC without ER-loss. Our analysis had several limitations; notably, our definition of ER-loss was based on prior treatment, we could not distinguish between de novo or recurrent metastatic disease and time of tissue collection was not standardized during the course of treatment. Thus, additional studies are needed to confirm these findings.

2 years ago

PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor)

PD-L1 expression • ER positive • HER-2 amplification • ER negative • HER-2 amplification + PD-L1 expression

MI Tumor Seek™

2years

Third- and Late Line Treatments of Metastatic Gastric Cancer: Still More to Be Done. (PubMed, Curr Oncol)

Overall, TAS-102, apatinib, regorafenib, nilotinib, trastuzumab, and pembrolizumab were demonstrated to be valid options in the third line scenario for mGC patient refractory to at least two lines of therapy. A multimodal approach based on chemotherapy, immunotherapy, targeted agents, a personalised nutritional programme as well as the research of new predictive biomarkers may pave the way to new strategies to identify the best treatment for each patient.

2 years ago

Review • Journal • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • MSI (Microsatellite instability)

PD-L1 expression • PD-L1 overexpression • HER-2 overexpression • HER-2 amplification • HER-2 amplification + PD-L1 expression

Keytruda (pembrolizumab) • Herceptin (trastuzumab) • AiTan (rivoceranib) • Tasigna (nilotinib) • Stivarga (regorafenib) • Lonsurf (trifluridine/tipiracil)

2years

HER2 in Uterine Serous Carcinoma: Testing platforms and implications for targeted therapy. (PubMed, Gynecol Oncol)

There was high concordance between HER2 positivity based on CISH and IHC. Rate of HER2 positivity is the lowest by NGS. Ultimately these testing platforms need to be validated by response to targeted therapy.

2 years ago

Journal • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog)

PD-L1 expression • HER-2 positive • HER-2 amplification • HER-2 amplification + PD-L1 expression

2years

HER-3 molecular classification, expression of PD-L1 and clinical importance in breast cancer. (PubMed, Bratisl Lek Listy)

PD-L1 expression was demonstrated in 3 out of 13 HER-3‑positive patients and 2 out of 2 HER-3‑positive TNBC patients. There was a strong correlation between positive HER-3 and PD-L1 TNBC expression (p = Keywords: breast cancer, HER family, overexpression, HER-3, HER-2, PD-L1, TNBC.

2 years ago

Journal • PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)

PD-L1 expression • HER-2 positive • HER-2 amplification • HR negative • ERBB3 expression • ERBB3 overexpression • HER-2 amplification + PD-L1 expression • PD-L1 expression + HER-2 overexpression • HER-2-H

2years

Comparison of the tumor immune microenvironment phenotypes in different breast cancers after neoadjuvant therapy. (PubMed, Cancer Med)

TNBC patients had significantly different immunoreactive TME compared with HR+ and HER2+ patients, suggesting potentially favorable outcomes for immunotherapy in these patients. Also, PD-L1+ could be a powerful predictor of pCR in TNBC patients after NAT.

2 years ago

Journal • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • BRCA (Breast cancer early onset) • CD4 (CD4 Molecule)

PD-L1 expression • HR positive • PD-L1 overexpression • HER-2 amplification • HER-2 expression • HER-2 amplification + PD-L1 expression

2years

HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR-2 (HER2) RECEPTOR EXPRESSION AND ITS DYNAMIC CHANGE IN OVARIAN CANCER PATIENTS (IGCS 2022)

Ovarian cancer patients with HER2 overexpression show a distinct histological, IHC, and genomic profile. HER2 targeting agent may serve as a potential option for BRCA wildtype patients, especially in the later lines of treatment.

2 years ago

Clinical • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker

PD-L1 expression • TP53 mutation • KRAS mutation • HER-2 overexpression • HER-2 amplification • PIK3CA mutation • HER-2 expression • PD-L1 underexpression • ARID1A mutation • BRCA wild-type • HER-2 amplification + PD-L1 expression

over2years

Molecular characterization of KRAS wild type tumors in patients with pancreatic adenocarcinoma. (PubMed, Clin Cancer Res)

KRAS-WT PDAC represents 10.7% of PDAC and is enriched with targetable alterations, including immuno-oncologic markers. Identification of KRAS-WT patients in clinical practice may expand therapeutic options in a clinically meaningful manner.

over 2 years ago

Journal • Tumor Mutational Burden • BRCA Biomarker • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • NRG1 (Neuregulin 1) • CD8 (cluster of differentiation 8) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • KMT2D (Lysine Methyltransferase 2D) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • KMT2C (Lysine Methyltransferase 2C) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • RAD50 (RAD50 Double Strand Break Repair Protein) • ARID2 (AT-Rich Interaction Domain 2) • NTRK (Neurotrophic receptor tyrosine kinase)

PD-L1 expression • TP53 mutation • KRAS mutation • TMB-H • MSI-H/dMMR • BRAF mutation • HER-2 amplification • ATM mutation • PALB2 mutation • KRAS wild-type • FGFR2 fusion • ALK fusion • RAS wild-type • PBRM1 mutation • BAP1 mutation • FGFR3 fusion • RAD50 mutation • FGF3 amplification • HER-2 amplification + PD-L1 expression • KRAS expression

gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • oxaliplatin

over2years

Co-occurring HER2 and PD-L1 expression in patients with HER2-positive trastuzumab-refractory gastric cancer (GC)/gastroesophageal junction adenocarcinoma (GEJA): biomarker analysis from the trastuzumab deruxtecan (T-DXd) DESTINY-Gastric03 trial (ESMO-GI 2022)

Discordance may be attributed to tissue heterogeneity. Substantial overlap between PD-L1 positivity and HER2 positivity supports combined administration of HER2-targeted agents and checkpoint inhibitors.

over 2 years ago

Clinical • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)

PD-L1 expression • HER-2 positive • HER-2 amplification • HER-2 expression • HER-2 positive + PD-L1 expression • HER-2 amplification + PD-L1 expression • PD-L1 expression + HER-2 overexpression • PD-L1 expression + HER-2 expression

FoundationOne® CDx • PD-L1 IHC 22C3 pharmDx • HercepTest

Enhertu (fam-trastuzumab deruxtecan-nxki)