trastuzumab biosimilar / Hetero - LARVOL DELTA

Efficacy of Neratinib-Based Therapy in ERBB2-Mutant Lung Adenocarcinomas: Findings From 2 International Phase 2 Studies. (PubMed, Clin Lung Cancer) - P2 | "Single-agent neratinib has limited activity in ERBB2-mutated lung cancers. Combinations with temsirolimus or trastuzumab did not markedly improve overall outcomes, producing durable responses in a limited subset of patients."

Journal • P2 data • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Response to a combination of T-DXd (Trastuzumab-Deruxtecan) plus Alectinib in a patient with ALK-TKI resistant ALK+ NSCLC harboring a common polymorphism MET N375S (DGHO 2025) - "From 2021 to 2023 the patient received sequential ALK-TKIs, including alectinib (9 months, mixed response ), lorlatinib (4 months, PD), brigatinib (4 months, PD) followed by atezo/bev/pac/carbo with a partial remission lasting for 6 months At no time point, on- or off target resistance alterations were detectable. In molecular pathology, NGS is primarily appointed to detect clinically relevant alterations, with a focus on hotspot mutations in driver oncogenes. However, a multitude of putatively benign polymorphisms are detected alongside and their contribution to a given therapy may be complex and potentially underestimated. Close genetic disease monitoring, continuous updates of annotation databases and discussions in molecular tumor boards may help to guide treatment options."

Clinical • Genetic Disorders • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Respiratory Diseases • Solid Tumor • ALK • EML4 • LRRTM4 • TP53

EORTC-1203 GITC "INNOVATION": Integration of trastuzumab (T), with or without pertuzumab (P), into perioperative chemotherapy of HER-2 positive stomach cancer: Overall survival results. (ASCO-GI 2025) - "CT was initially cisplatin (80 mg/m2 d1) and capecitabine (2 x 1000 mg/m2/d d1) for 3 cycles before and after surgery... Non-significant advantages in terms of PFS and OS were observed for the addition of T to CT before, but not after the amendment. CT+T+P was detrimental. These results reflect the challenge of using mpRR as surrogate for survival in the perioperative treatment of GC."

Clinical • Late-breaking abstract • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

[VIRTUAL] Herpet study- PET imaging of HER2 expression in breast cancer using the novel Affibody tracer [18F]GE-226, a first in patient study (SABCS 2020) - "GE-226 is a radiolabelled Affibody® tracer which binds to the HER2 receptor with high affinity at a different epitope than trastuzumab. Conclusions [18F]GE-226 imaging is well tolerated and shows promise for imaging of HER2 positive breast cancer. Further studies with this agent are now planned."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Risk of peripheral neuropathy with trastuzumab emtansine: A systematic review and meta-analysis of published phase 3 randomized controlled trials (SABCS 2019) - "Patients in the control arms received variable systemic therapies across trials: a taxane based regimen was used in GATSBY, KRISTINE, and MARIANNE trials; a capecitabine and lapatinib combination was used in EMILIA trial; and a treatment of physician’s choice was used in TH3RESA trial. Our meta-analysis demonstrated the relative risk of any grade peripheral neuropathy was not significantly higher in the T-DM1 containing regimens compared to other therapies in patients with HER2-positive cancers."

P3 data • Retrospective data • Review

Relative risk of grade 3 and higher hematological toxicities with trastuzumab emtansine: A systematic review and meta-analysis of published phase 3 randomized controlled trials (SABCS 2019) - "Patients in the control arms received variable systemic therapies across trials: taxane based regimens were used in GATSBY, KRISTINE, and MARIANNE trials; capecitabine and lapatinib combination was used in EMILIA trial; treatments of physician’s choice were used in TH3RESA trial; and trastuzumab alone was used in KATHERINE trial. T-DM1 was associated with increased risk of grade 3 and higher thrombocytopenia, but reduced risk of grade 3 and higher neutropenia compared to control regimens. The exact mechanism of these findings is not clear, yet they may have some implications in adopting appropriate therapeutic strategies for the patients. The patients who are on T-DM1, a careful monitoring of the platelet will be helpful for the early identification of thrombocytopenia and initiation of appropriate interventions."

P3 data • Relative risk • Retrospective data • Review

Characterizing the tumor and immune microenvironment through treatment to predict response to neoadjuvant HER2-targeted therapy using the Digital Spatial Profiler (SABCS 2019) - P2; "Using this technology, we assayed archival tissue from 28 patients with HER2-positive breast cancer from the TRIO-B07 (NCT00769470) clinical trial, who were treated with trastuzumab, lapatinib, or both, followed by standard chemotherapy plus HER2-targeted therapy. In this study, we used DSP and a panCK enrichment strategy to retrospectively delineate the changes that occurred in tumor cells and co-localized immune cells during HER2-targeted therapy. In comparison to traditional or multiplexed IHC, DSP allows for simultaneous profiling of a large number of markers, enabling the characterization of multiple cancer signaling pathways and immune markers on a single tissue specimen. This study demonstrates the utility of pancytokeratin-enriched spatial proteomic profiling to characterize treatment-associated changes and identify predictive biomarkers.NanoString’s Digital Spatial Profiler is for Research Use Only."

Clinical • CD8 • Cytokeratin • HER2

Relative risk of peripheral neuropathy with trastuzumab emtansine compared to taxane-based regimens in HER2-positive cancers: A systematic review and meta-analysis of published phase 3 randomized controlled trials (SABCS 2019) - "Background: Trastuzumab Emtansine (T-DM1) is a HER2-targeted antibody-drug conjugate consisting of anti-HER2 IgG1 antibody trastuzumab and maytansine derivative DM-1. Our meta-analysis demonstrated the pooled relative risk of any grade peripheral neuropathy and peripheral sensory neuropathy was significantly lower with the T-DM1 containing regimens compared to the taxane-based regimens for HER2-positive cancers. This could be an area of consideration when choosing therapy for the patients who are at higher risk of developing or have pre-existing peripheral neuropathy.Table 1P: PertuzumabBC: Breast Cancer"

P3 data • Relative risk • Retrospective data • Review • HER2

[VIRTUAL] Predictors of 18F-fluorodeoxyglucose (F) positron-emission tomography (PET)-driven disease detection in patients (pts) with HER2[+] early breast cancer (EBC). A substudy of the PHERGain trial (ESMO-BC-I 2020) - P2 | "Background: PHERGain (NCT03161353) is assessing the early metabolic response by F-PET to neoadjuvant chemotherapy-free treatment with trastuzumab and pertuzumab and the opportunity of chemotherapy de-escalation with a response-adapted strategy in pts with HER2[+] EBC. Taking into account the clinical and biological heterogeneity of HER2[+] disease, these results may need to be considered for an appropriate selection of PET[+] pts in HER2[+] EBC.Legal entity responsible for the study: MedSIR. Funding: Has not received any funding."

Clinical • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • AKT2 • FDG PET • FLT3 • HER-2 • HIF1A • LDHA • MRI

[VIRTUAL] PIK3CA mutations in HER2-positive early breast cancer patients enrolled in the adjuvant randomized short-HER study (ESMO-BC-I 2020) - P3 | " The ShortHER trial randomized 1254 patients with HER2-positive early breast cancer to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. Within the HER2-enriched molecular subtype, PIK3CA mutated patients showed better DFS as compared to PIK3CA wild-type patients. These results highlight the need to integrate multiple biomarkers in order to dissect the heterogeneity of HER2-positive breast cancer.Legal entity responsible for the study: University of Padua. Funding: Italian Medicines Agency (AIFA, grant FARMS5KR); Italian Association for Cancer Research (AIRC, grant MFAG-15938)."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

[VIRTUAL] Prognostic value of the immune infiltration score in early breast cancer patients receiving dual HER2 blockade with trastuzumab and pertuzumab: An exploratory analysis of a randomized clinical trial (ESMO-BC-I 2020) - P2 | "Our analysis demonstrates an independent prognostic value of IIS in patients receiving trastuzumab/pertuzumab-based neoadjuvant chemotherapy.Legal entity responsible for the study: The authors. Funding: Has not received any funding. Clinical trial identification: NCT00976989."

Clinical • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

[VIRTUAL] PIK3CA mutations in HER2-positive early breast cancer patients enrolled in the adjuvant randomized short-HER study (ESMO-BC-I 2020) - P3 | " The ShortHER trial randomized 1254 patients with HER2-positive early breast cancer to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. Within the HER2-enriched molecular subtype, PIK3CA mutated patients showed better DFS as compared to PIK3CA wild-type patients. These results highlight the need to integrate multiple biomarkers in order to dissect the heterogeneity of HER2-positive breast cancer.Legal entity responsible for the study: University of Padua. Funding: Italian Medicines Agency (AIFA, grant FARMS5KR); Italian Association for Cancer Research (AIRC, grant MFAG-15938)."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

[VIRTUAL] Prognostic value of the immune infiltration score in early breast cancer patients receiving dual HER2 blockade with trastuzumab and pertuzumab: An exploratory analysis of a randomized clinical trial (ESMO-BC-I 2020) - P2 | "Our analysis demonstrates an independent prognostic value of IIS in patients receiving trastuzumab/pertuzumab-based neoadjuvant chemotherapy.Legal entity responsible for the study: The authors. Funding: Has not received any funding. Clinical trial identification: NCT00976989."

Clinical • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

[VIRTUAL] Predictors of 18F-fluorodeoxyglucose (F) positron-emission tomography (PET)-driven disease detection in patients (pts) with HER2[+] early breast cancer (EBC). A substudy of the PHERGain trial (ESMO-BC-I 2020) - P2 | "Background: PHERGain (NCT03161353) is assessing the early metabolic response by F-PET to neoadjuvant chemotherapy-free treatment with trastuzumab and pertuzumab and the opportunity of chemotherapy de-escalation with a response-adapted strategy in pts with HER2[+] EBC. Taking into account the clinical and biological heterogeneity of HER2[+] disease, these results may need to be considered for an appropriate selection of PET[+] pts in HER2[+] EBC.Legal entity responsible for the study: MedSIR. Funding: Has not received any funding."

Clinical • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • AKT2 • FDG PET • FLT3 • HER-2 • HIF1A • LDHA • MRI

First-line pembrolizumab (P), trastuzumab (T), capecitabine (C) and oxaliplatin (O) in HER2-positive metastatic esophagogastric adenocarcinoma (ESMO 2019) - P3; "40% remain on therapy, and so the primary endpoint should be reached by 9/19. Updated survival, correlative studies and will be presented. These promising preliminary safety and efficacy results led to initiation of a definitive phase III Keynote 811 trial (NCT03615326)."

Clinical • IO biomarker • PD(L)-1 Biomarker • Tumor mutational burden • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

[VIRTUAL] Targeted therapies: How can CT imaging improve evaluations and help understand mechanism of drug action? (ASCO 2020) - P2a/2b | "Background: We compared the therapeutic response between Varlitinib plus Capecitabine (VC) and Lapatinib plus Capecitabine (LC) by stratifying changes in tumor’s longest diameter (LD) and volume (VOL) per tumor location in patients with HER2+ metastatic breast cancer after trastuzumab therapy. Differential imaging responses were found across treatment arms and tumor locations. The stratification of changes provides new insights into responses of targeted therapies and more accurate drug comparisons. The stratification is a promising approach to better understand therapy mechanisms of action behind tumor heterogeneity."

Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

[VIRTUAL] Concordance of multispectral immunofluorescence (mIF) with programmed death ligand 1 (PD-L1) and stromal tumor infiltrating lymphocyte (sTILs) clinical assays in early-stage breast cancer (BC). (ASCO 2020) - P1 | "mIF is concordant with SP142 and sTIL prognostic assays, but with increased precision to quantify treatment related changes. Regression modeling can dramatically improve the utility of mIF as a surrogate immune-based biomarker. Our approach is being utilized in ongoing phase II studies to compare the activity of pembrolizumab +/- locoregional cytokines (IRX-2) in triple negative BC, and paclitaxel/trastuzumab +/- pembrolizumab +/- pertuzumab in HER2-positive BC."

Clinical • IO biomarker • Breast Cancer • Oncology • Solid Tumor • CD163 • CD8 • Cytokeratin • FOXP3 • HER-2 • PD-L1

Radiomics features on CT scans to predict response to HER2-targeted therapy of hepatic metastases from colorectal cancer. (ASCO 2019) - P2; " The dataset is composed of 39 extended RAS wild type patients with amplified HER2 mCRC enrolled in the HERACLES trial (NCT03225937) that received either a lapatinib+trastuzumab treatment (n = 23) or a pertuzumab+ trastuzumab-emtansine treatment (n = 16). CTTA might help in stratifying different behaviors of mCRC, opening the way for lesion-specific therapies, with conceivable cost and life savings. Further extended analysis is needed to better characterize and validate predictive value of these biomarkers."

First-line pembrolizumab (P), trastuzumab (T), capecitabine (C) and oxaliplatin (O) in HER2-positive metastatic esophagogastric adenocarcinoma. (ASCO 2019) - P2; "Most pts (51%) remain on therapy, and so the primary endpoint should be reached by 6/19. Updated survival, correlative studies and will be presented. These promising preliminary safety and efficacy results led to initiation of a definitive phase III Keynote 811 trial."

Clinical • IO biomarker • PD(L)-1 Biomarker • Tumor mutational burden • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Hyperprogressive disease after two cycles of immunotherapy in HER-2 positive metastatic gastric cancer (AACR-NCI-EORTC 2019) - P1/2; "Pembrolizumab and nivolumab, an anti-programmed death ligand 1 (anti PD-L1) agent, has approved in treatment of advanced or metastatic gastric cancer previously treated with two or more therapies...She was then enrolled in the currently ongoing, investigator-initiated PANTHERA trial (NCT02901301), a phase Ib/II study of first line pembrolizumab in combination with trastuzumab, capecitabine and cisplatin... Among 41 patients enrolled in ongoing PANTHERA trial, only one patient progressed after 2 cycles of treatment . To our knowledge, this is the first documented hyperprogression in advanced or metastatic gastric cancer after treatment with pembrolizumab. Although mechanisms behind HPD remain to be elucidated, the discrepancy in pre and post IHC results points out that tumor heterogeneity may play a role."

Clinical • IO biomarker • PD(L)-1 Biomarker • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CA125 • CA724 • HER-2

HER2 positive gastric carcinoma: Mean HER2 expression is associated with high variation in HER2 test results between local and central pathology and poorer survival (DGHO 2019) - P=N/A; "Background: For HER2+ Gastric Cancer (GC) trastuzumab is the only approved targeted therapy addressing the membrane-bound receptor tyrosine kinase HER2. Discrepancies between local and central HER2 assessment in GC were significant and mostly found in tumor specimens with intermediate HER2 expression levels. Borderline HER2-positivity and heterogeneity of the marker expression should be considered as a resistance factor for HER2-directed therapy. HER2-cut-offs should be reconsidered and a more detailed reporting of the HER2 status including the quantification of stained tumor cells might be of value."

Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

mRNA expression of specific HER ligands and their association with clinical outcome in patients with metastatic breast cancer treated with trastuzumab. (PubMed, Oncol Lett) - "In patients with de novo MBC, high EGF expression was associated with a non-significant prolongation of TTP (HR=0.52, P=0.080) and significantly longer survival (HR=0.40, P=0.020). The present study examined clinical and biological implications of specific genes and it was concluded that their expression has an impact on the outcome of trastuzumab-treated patients with MBC."

Clinical • Clinical data • Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • BTC • HBEGF • HER-2 • NRG1 • TGFB1

Clinical Significance of Major Angiogenesis-Related Effectors in Patients with Metastatic Breast Cancer Treated with Trastuzumab-based Regimens. (PubMed, Cancer Res Treat) - "A trend towards longer progression free survival (PFS) was detected univariately for patients with HER2-negative tumors and high expression of VEGFR2, (HR=0.60, p=0.059). VEGFR1 and VEGFR2 seem to have significant prognostic value in BC patients with metastatic disease treated with trastuzumab-based regimens."

Clinical • Journal • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • FLT1 • FLT4 • HER-2 • KDR • PCR • VEGFC

[VIRTUAL] Unraveling trastuzumab emtansine resistance in HER2-positive advanced breast cancer: GEICAM KATIA study (ESMO 2020) - P=N/A | "Funding: Roche. Clinical trial identification: NCT03829306."

IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CCNB1 • HER-2 • PD-L1

Ado-trastuzumab emtansine in patients with HER2 amplified salivary gland cancers (SGCs): Results from A Phase II basket trial. (ASCO 2019) - P2; "ORR was 90% (9/10, 95% CI 56-100%) including 5 complete responses after prior trastuzumab, pertuzumab and anti-androgen therapy. Ado-trastuzumab emtansine is highly efficacious in patients with HER2 amplified SGCs as identified by NGS. This study has met its primary endpoint, and cohort expansion is warranted to confirm these results. Clinical trial information: NCT02675829"

Clinical • P2 data • HER2 Positive Breast Cancer • Oncology