lapatinib / Generic mfg. - LARVOL DELTA

Zanidatamab (Zani) + chemotherapy (Chemo) for patients (Pts) with HER2-expressing metastatic breast cancer (mBC): Final results of a phase I trial (ESMO-BC 2025) - P1 | "We report the final analysis of a phase I trial of zani + chemo in pts with HER2-expressing mBC. Part 3 of the phase I trial (NCT02892123) evaluated zani + chemo (paclitaxel [pac], capecitabine [cap] or vinorelbine [vin]) or zani + cap + tucatinib (tuc) in pts with HER2-expressing mBC...Prior (>5% of pts) anti-HER2 therapies included trastuzumab (93%), T-DM1 (91%), pertuzumab (80%), lapatinib (24%), T-DXd (9%), tuc (9%), and neratinib (7%)... Zani + chemo had a manageable safety profile and good tolerability with promising antitumour activity and durable responses in heavily pretreated pts with HER2-expressing mBC. Among pts with HER2+ mBC with prior HER2-targeted regimens, adding zani to chemo showed encouraging PFS."

Clinical • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Long-term outcomes of patients with HER2-positive breast cancer and rare special histologies in the ALTTO trial [BIG 2-06/NCCTG N063D (Alliance)] (ESMO-BC 2025) - P3 | "Background: Rare special types (rST) of breast cancer (BC), are underrepresented in HER2-positive (HER2+) cases, with limited data on clinical features and outcomes when treated with adjuvant trastuzumab (T). This study evaluates rST prognostic value in that setting. The ALTTO trial was a phase III, multicenter, randomized study evaluating T alone or with lapatinib as adjuvant therapy in patients (pts) with HER2+ early BC... Despite distinct baseline features and risk profiles, our study did not show significant survival differences across histological subtypes receiving T-based adjuvant treatment. Table: 226P DFS and OS by rST vs NST (n=6162, mixed ILC-NST not included)"

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

Adjuvant aromatase inhibitor or tamoxifen in patients with hormone receptor-positive/HER2-positive early breast cancer: An exploratory analysis from the ALTTO (BIG 2-06) trial (SABCS 2025) - "The present analysis investigated the efficacy of different types of ET in pts with centrally tested HR+/HER2+ EBC treated with modern chemotherapy (CT) and trastuzumab (T)-based regimens at 10-year follow-up.Patients and ALTTO (BIG 2-06) is an international phase 3 trial in pts with HER2+ EBC randomized to 4 adjuvant anti-HER2 treatments with CT: T alone, lapatinib (L) alone, their sequence (T->L) or their combination (T+L). In this large 10-year follow-up analysis of pts with centrally tested HR+/HER2+ EBC treated with modern CT+anti-HER2-based therapy in the ALTTO trial, the use of AI was associated with significantly improved DFS and TTDR without differences in OS. The DFS benefit of AI was observed in both premenopausal and postmenopausal pts. These data may help optimizing adjuvant ET choices in pts with HR+/HER2+ EBC and shed light on the need of designing ad hoc clinical trials in this setting."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • HER-2

Safety, tolerability, pharmacokinetics, and antitumor activity of SHR-A1811 in HER2-expressing/mutated advanced solid tumors: A global phase 1, multi-center, first-in-human study (AACR 2023) - "Background: SHR-A1811 is an ADC comprised of a humanized anti-HER2 monoclonal antibody (trastuzumab), a cleavable linker, and a DNA topoisomerase I inhibitor payload. SHR-A1811 was well-tolerated and showed promising antitumor activity in heavily pretreated advanced solid tumors.Table 1. Subgroup analyses of ORRNo. of prior treatment lines in metastatic setting in all pts (N=250)HER2 positive BC (N=108)HER2-low BC (N=77)Other tumor types (N=65)≤381.8% (45/55)58.7% (27/46)36.7% (18/49)>381.1% (43/53)51.6% (16/31)31.3% (5/16)Prior anti-HER2 therapies in pts with BC (N=185)*HER2 positive BC (N=108)HER2-low BC (N=77)All BC (N=185)Any82.2% (88/107, 73.7-89.0)68.8% (11/16, 41.3-89.0)80.5% (99/123, 72.4-87.1)Trastuzumab81.9% (86/105, 73.2-88.7)75.0% (9/12, 42.8-94.5)81.2% (95/117, 72.9-87.8)Pertuzumab83.0% (39/47, 69.2-92.4)100% (5/5, 47.8-100)84.6% (44/52, 71.9-93.1)Pyrotinib86.9% (53/61, 75.8-94.1)71.4% (5/7, 29.0-96.3)85.3% (58/68, 74.6-92.7)Lapatinib80.0% (28/35,..."

Clinical • Metastases • P1 data • PK/PD data • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • HER-2

Trastuzumab deruxtecan vs physician’s choice in patients with HER2+ unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine: primary results of the randomized, phase 3 study DESTINY-Breast02 (SABCS 2022) - P2, P3 | "Methods Pts with HER2+ mBC were randomized 2:1 to receive T-DXd or TPC (trastuzumab + capecitabine or lapatinib + capecitabine) and stratified by hormone receptor (HR) status (HR+/HR-), prior pertuzumab treatment, and history of visceral disease. Conclusions Results from DESTINY-Breast02 confirmed the clinical benefit and superiority of T-DXd over conventional chemotherapy-based regimens in pts with HER2+ mBC previously treated with T-DM1, as evidenced by significant and clinically meaningful improvements in PFS and OS. These data, together with earlier reported results from the DESTINY-Breast03 study of T‑DXd vs T-DM1 solidify T-DXd as an optimal treatment option in pts with progressive HER2+ mBC across broad settings."

Clinical • P3 data • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • HER-2

Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial. (PubMed, Lancet) - P3 | "DESTINY-Breast02 shows the favourable benefit-risk profile of trastuzumab deruxtecan in patients with HER2 positive metastatic breast cancer, as previously reported in DESTINY-Breast01, and is the first randomised study to show that one antibody-drug conjugate can overcome resistance to a previous one."

Journal • Metastases • P3 data • Alopecia • Breast Cancer • Fatigue • HER2 Breast Cancer • HER2 Positive Breast Cancer • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2

Trastuzumab deruxtecan (T-DXd) vs treatment of physician's choice (TPC) in patients (pts) with HER2+ metastatic breast cancer (mBC) previously treated with trastuzumab emtansine (T-DM1): Updated overall survival (OS) results of the randomized phase III DESTINY-breast (DB-)02 study (ESMO-BC 2024) - P3 | "Methods Pts with HER2+ mBC were randomly assigned 2:1 to T-DXd or TPC (trastuzumab + capecitabine [cap] or lapatinib + cap). Conclusions Results reinforce the substantial benefit of T-DXd over TPC in pts with HER2+ mBC previously treated with T-DM1, demonstrated by clinically meaningful improvement in OS, PFS, and PFS2. The safety profile of T-DXd continues to be manageable, with no long-term toxicity observed with longer F/U."

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Interstitial Lung Disease • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2

The effectiveness of post-T-DXd treatments in patients with HER2-positive metastatic breast cancer: A nationwide Japanese cohort study (EN-SEMBLE) (SABCS 2024) - P=N/A | "The subsequent regimens (1st post-T-DXd treatment) after T-DXd discontinuation were anti-HER2 antibody (trastuzumab, pertuzumab)–containing regimens, 54.4% (361/664); anti-HER2 TKI–containing regimens (lapatinib, other anti-HER2 TKIs), 17.0% (113/664); ADC (trastuzumab emtansine), 1.8% (12/664); and others, 26.8% (178/664). About half of the pts received anti-HER2 antibody regimens in the 1st treatment after T-DXd. No differences were observed between anti-HER2 antibody and TKI-based regimens in terms of rwPFS, rwTTNT, or OS. Post-T-DXd treatments were generally safe in pts who had discontinued T-DXd due to ILD, with 3.4% of exacerbation."

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

Patient-reported outcomes (PROs) from DESTINY-Breast02, a randomized phase 3 study of trastuzumab deruxtecan (T-DXd) vs treatment of physician's choice (TPC) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC) (ESMO-BC 2023) - P3 | "Methods Pts with HER2+ (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization amplified) T-DM1–resistant/refractory mBC were assigned 2:1 to T-DXd or TPC (trastuzumab + capecitabine or lapatinib + capecitabine). TDD was longer on all measured QLQ-C30 subscales, except for nausea/vomiting, for pts receiving T-DXd vs TPC. These results continue to support the benefit of T-DXd in pts with T-DM1–resistant HER2+ mBC."

Clinical • Metastases • P3 data • Patient reported outcomes • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Pain • Solid Tumor • HER-2

DSN1 drives breast cancer progression via cell cycle regulation: diagnostic and therapeutic implications. (PubMed, Front Oncol) - "Drug sensitivity analysis showed that the DSN1 high expression group was resistant to drugs such as Epirubicin, Cyclophosphamide, Ribociclib, and Palbociclib, but relatively sensitive to tamoxifen and lapatinib. DSN1 contributes to breast cancer progression by modulating cell cycle pathways, making it a potential diagnostic and therapeutic target with clinical applicability."

Journal • Breast Cancer • Oncology • Solid Tumor • CCNB1 • CCND1 • CDK4 • CDK6

Mapping the Kinase Inhibitor Landscape in Canine Mammary Carcinoma: Current Status and Future Opportunities. (PubMed, Animals (Basel)) - "In vitro studies demonstrate that palbociclib, alpelisib, everolimus, and lapatinib inhibit growth and signalling in CMC cell lines. Translational research, including xenograft and organoid models, followed by clinical trials in dogs, is required. Gaining this knowledge could lead to targeted treatment for dogs while advancing comparative understanding of mammary cancer biology across species."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

[Retracted] EGFR/HER2 inhibitors effectively reduce the malignant potential of MDR breast cancer evoked by P‑gp substrates in vitro and in vivo. (PubMed, Oncol Rep) - "Following the publication of the above article, it was drawn to our attention by a concerned reader that the pairs of data panels showing the results for the Paxitaxel (or Epirubicin) + Lapatinib and the Paxitaxel (or Epirubicin) + Trastuzumab experiments respectively in Fig. The Editor apologizes to the readership of the Journal for any inconvenience caused. [Oncology Reports 35: 771‑778, 2016; DOI: 10.3892/or.2015.4444]."

Journal • Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Translational Breast Cancer Research Consortium Trial 022: Neratinib and Trastuzumab-Emtansine for HER2+ breast cancer brain metastases (BCBM) (SABCS 2022) - "We previously reported that neratinib monotherapy is associated with a volumetric central nervous system objective response rate (CNS ORR) of 8%, whereas the combination of neratinib and capecitabine resulted in a volumetric CNS ORR of 49% (in lapatinib-naïve pts)...Across Cohorts 4A-4C, the median number of prior lines of chemotherapy prior to enrollment was 2 (range 1-10); 25% received prior lapatinib and no patients received prior tucatinib... Intracranial activity was observed for the combination of neratinib plus T-DM1 across all three enrolled cohorts, including those with prior T-DM1 exposure, suggesting synergistic effects of this treatment combination. Our data provide additional evidence for consideration of neratinib- based combinations in pts with HER2+ BCBM."

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

Trastuzumab duocarmazine versus physician's choice therapy in pre-treated HER2-positive metastatic breast cancer: Final results of the phase III TULIP trial (ESMO 2023) - P3 | "Methods The TULIP trial randomly assigned patients with HER2-positive locally advanced or MBC with ≥2 previous HER2-targeting MBC regimens or pretreated with T-DM1, in a 2:1 ratio between T-Duo (1.2 mg/kg q3w) and PC. PC could be either trastuzumab combined with capecitabine or vinorelbine or eribulin or lapatinib plus capecitabine...The final OS results confirm a trend towards a numerically prolonged OS (statistically non-significant) in the T-Duo group compared with PC group. Safety was aligned with the primary analysis, with no new signals identified."

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Cost Variation and Affordability of Oral Targeted Cancer Therapy in India: Comparison of Branded and Janaushadhi Products. (PubMed, Cureus) - "Percentage cost variation ranged from 8% (Bosutinib) to 14,774.74% (Midostaurin), with corresponding cost ratios up to 148.75...Absolute savings versus median branded costs ranged from ₹2,968 (Dasatinib) to ₹25,270 (Lapatinib), while percentage savings ranged from 58.89% (Dasatinib) to 91.32% (Imatinib)...However, limited PMBJP coverage restricts their overall benefit. Expanding Janaushadhi availability, improving price regulation, and encouraging rational prescribing are crucial to ensure equitable access to targeted cancer therapies in India."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Oral Cancer • Solid Tumor • ABL1 • BCR • CDK4

Trastuzumab plus lapatinib or chemotherapy in patients with HER2-overexpressed advanced breast cancer: a randomized, phase II trial (GIM12-TYPHER). (PubMed, Oncologist) - "While efficacy differences were not significant, trastuzumab with lapatinib showed better QoL despite higher adverse event rates, suggesting it may be a viable chemotherapy-free option for pretreated HER2-positive advanced breast cancer."

Journal • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Identification of Druggable Binding Sites and Small Molecules as Modulators of TMC1 (ARO 2026) - "Unfortunately, ototoxic drugs such as aminoglycoside antibiotics and cisplatin exploit these channels to enter hair cells, often causing irreversible auditory and vestibular dysfunction...Docking results confirmed consistent binding of classical blockers such as benzamil and tubocurarine, as well as novel hits including cepharanthine, posaconazole, and lapatinib... This integrative approach combining pharmacophore modeling, molecular dynamics, docking, and in vitro validation establishes a versatile platform for discovering modulators of TMC1. The identification of multiple binding sites within the channel pore and validation of FDA-approved drugs as effective blockers highlights the translational potential of this work. By expanding the chemical space of candidate molecules, this study not only provides insights into the pharmacological modulation of TMC1 but also offers a rational framework for developing otoprotective therapies to counteract drug-induced hearing loss."

Otorhinolaryngology

Radiation therapy combined with tyrosine kinase inhibitors in 826 patients with HER2-positive breast cancer brain metastases: a systematic review and network meta-analysis. (PubMed, Neurosurg Rev) - "Bayesian network meta-analysis (NMA) was conducted to integrate direct and indirect comparisons, addressing the lack of head-to-head trials. Eleven studies (2 RCTs, 9 retrospective; 826 patients) evaluated four treatment strategies: pyrotinib + RT, pyrotinib alone, RT alone, and lapatinib + RT. In contrast, lapatinib + RT appeared to offer limited benefit and a higher risk of SAEs. Further randomized controlled trials are needed to validate these findings."

Clinical • Journal • Retrospective data • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Efficacy and safety of pyrotinib-based regimens in patients with HER2-positive stage III/IV breast cancer: a real-world retrospective study in China. (PubMed, PeerJ) - "A subgroups comparison found that significant differences were observed in patients who had not used lapatinib (P = 0.016), had a number of metastatic sites ≤ 2 (P = 0.011), were intolerant to trastuzumab (P = 0.004), and were on first-line pyrotinib treatment (P = 0.036), with these patients having median progression-free survival lengths of 13.0 months, 15.9 months, 23.5 months, and 23.5 months, respectively. In addition, a rare positive fecal occult blood profile (5.4%) was observed. Pyrotinib-based regimens have shown satisfactory clinical efficacy in HER2-positive stage III/IV BC patients, and pyrotinib is well tolerated with manageable adverse events."

Journal • Real-world evidence • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Updated overall survival (OS) results from the phase 3 PHOEBE trial of pyrotinib versus lapatinib in combination with capecitabine in patients with HER2-positive metastatic breast cancer (SABCS 2021) - P3 | "With extended follow-up, pyrotinib plus capecitabine demonstrated statistically significant OS improvement compared with lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer after trastuzumab and chemotherapy. This updated analysis of overall survival in the PHOEBE trial reaffirmed pyrotinib plus capecitabine as an established treatment option in this patient population. Data are median (95% CI)."

Clinical • Combination therapy • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • EGFR • ER • ERBB4 • HER-2 • PGR

Downregulation of SLC12A5 in glioblastoma multiforme: a novel prognostic biomarker associated with brain edema and radiomic features. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Drug sensitivity screening identified six small molecules (PD0325901, ERK-6604, paclitaxel, ribociclib, TAF1, and lapatinib) that targeted SLC12A5-related pathways. Crucially, multivariate Cox regression analysis confirmed that SLC12A5 was an independent prognostic factor (HR p = 0.04). This study established SLC12A5 as a novel biomarker for GBM, uniquely bridging molecular dysregulation, edema pathogenesis, and radiomics with implications for prognosis and targeted therapy."

Biomarker • Journal • Brain Cancer • CNS Disorders • Glioblastoma • Oncology • Solid Tumor • LOX • MMP9 • SERPINH1 • TAF1 • VSNL1

Anti-HER2-targeted therapies: effects on human in vitro blood-brain barrier models. (PubMed, Front Drug Deliv) - "Established therapies such as trastuzumab, pertuzumab, trastuzumab/pertuzumab, lapatinib and tucatinib are widely used and are selectively toxic to HER2-positive breast cancer cell line. In conclusion, we demonstrate different time- and concentration-dependent effects of anti-HER2-targeted therapies for the treatment of advanced HER2-positive breast cancer on the BBB in vitro. Further experiments are required to assess the clinical relevance of our results."

Journal • Preclinical • Brain Cancer • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ABCB1 • ABCG2 • CCL2 • CD34 • CLDN5 • OCLN • SLC2A1

HER2DX and pathological complete response in HER2-positive breast cancer: a combined analysis of 4 neoadjuvant studies (ESMO-BC 2023) - "All patients were treated with neoadjuvant trastuzumab (n=568) in combination with multi-agent chemotherapy (n=282), a single taxane (n=286), pertuzumab (n=264), lapatinib (n=103) or without a second anti-HER2 drug (n=201). The pCR rates in HER2DX pCR-low tumors were ≤30.0% regardless of type of treatment. Conclusions HER2DX might help identify patients with HER2-positive breast cancer who benefit from neoadjuvant dual HER2 blockade in combination with a single taxane."

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

Final analysis of the ALTTO trial: adjuvant trastuzumab in sequence or in combination with lapatinib in patients with HER2-positive early breast cancer [BIG 2-06/NCCTG N063D (Alliance)]. (PubMed, ESMO Open) - P3 | "With a longer follow-up, no significant improvement was observed in DFS in patients treated with dual anti-HER2 blockade with lapatinib + trastuzumab compared to trastuzumab alone. The 10-year survival rates for the combination group are consistent with other studies that have explored dual anti-HER2 therapy."

Clinical • Combination therapy • Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

ACE-Breast-02: A pivotal phase II/III trial of ARX788, a novel anti-HER2 antibody-drug conjugate (ADC), versus lapatinib plus capecitabine for HER2+ advanced breast cancer (ABC). (ASCO 2024) - "Research Funding: No funding sources reported. ARX788 significantly prolonged PFS comparing to LC in patients with HER2+ ABC previously treated with trastuzumab and taxane. While ocular toxicity and interstitial lung disease were common and manageable, its hematological and GI toxicities under no prophylactic premedication compared favorably with already available ADCs."

Metastases • P2/3 data • Breast Cancer • Dermatology • Dry Eye Disease • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Interstitial Lung Disease • Oncology • Ophthalmology • Pulmonary Disease • Respiratory Diseases • Solid Tumor