lapatinib / Generic mfg. - LARVOL DELTA

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

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

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

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

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

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

A CFH- and SPINT2-based prognostic signature for cholangiocarcinoma. (PubMed, J Gastrointest Oncol) - "Drug sensitivity analysis demonstrated that the high-risk group was more sensitive to gemcitabine, cisplatin, poly(ADP-ribose) polymerase (PARP) inhibitors, and mammalian target of rapamycin (mTOR) inhibitors, whereas the low-risk group was more sensitive to lapatinib. High-risk patients, characterized by fibroblast-derived CFH enrichment and malignant-cell SPINT2 loss, exhibit an immunosuppressive microenvironment and may be more suitable for gemcitabine-based chemotherapy or PARP/mTOR inhibitors, whereas low-risk patients may benefit from less intensive adjuvant strategies or HER2/EGFR-targeted lapatinib. Prospective validation is warranted before clinical implementation."

Journal • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • HER-2 • SPINT2

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

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

Long-term outcomes of patients with HER2-positive invasive lobular carcinoma in the ALTTO trial (BIG 2-06/NCCTG N063D [Alliance]). (ASCO 2025) - P3 | " ALTTO was a multicenter, randomized phase III trial evaluating the efficacy of trastuzumab, lapatinib, their sequence, or combination as adjuvant therapy in pts with HER2+ early BC. Long-term outcomes were comparable between ILC and NST in HER2+ early BC treated with trastuzumab-containing regimens. The higher incidence of CNS metastases in ILC highlights its unique relapse pattern, necessitating further investigation to optimize treatment. High discordance between central and local pathology emphasizes the need for standardized histological review in trials and treatment decisions."

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

Comparing Trastuzumab and/or Lapatinib-Based Neoadjuvant Regimens in HER2-positive breast cancer: A Meta-Analysis Stratified by Chemotherapy Backbone (ESMO 2026) - No abstract available

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

Repurposing Anticancer Drugs in Parkinson's Treatment: Molecular Pathways Driving Neuroprotection and Therapeutic Advancement. (PubMed, Mol Neurobiol) - "Ixazomib enhances α-synuclein clearance via autophagy in preclinical models. Nilotinib showed poor CNS penetration (< 0.3% in CSF), resulting in worsening motor outcomes. Relatlimab, trehalose, and lapatinib demonstrated preclinical benefits through inhibition of α-synuclein spread, mTOR-independent autophagy, and multi-pathway neuroprotection, respectively. The AZA-PD Phase 2 trial (azathioprine) demonstrated a favourable safety and tolerability profile and offered valuable insights into peripheral immune modulation in early PD, though it did not meet its primary endpoint of slowing disease progression...Mechanistic convergence provides a rationale for repurposing drugs; however, clinical success requires addressing the unique challenges of neurodegeneration. Future approaches should focus on precision medicine, innovative delivery systems, and multi-target interventions rather than direct therapeutic translation."

Journal • Review • CNS Disorders • Immune Modulation • Immunology • Metabolic Disorders • Movement Disorders • Oncology • Parkinson's Disease • Targeted Protein Degradation

Design, synthesis, and biological evaluation of quinolin-2-one/thiazole hybrids as multi-targeted antiproliferative agents inducing caspase-dependent apoptosis. (PubMed, Sci Rep) - "Among them, compound 6b emerged as the most potent lead candidate, with a mean IC50 of 4.20 µM, representing a 1.7-fold higher potency than the reference drug, sorafenib (IC50 = 6.80 µM)...Enzymatic assays revealed that 6b acts as an efficient multi-kinase inhibitor, effectively targeting EGFR (IC50 = 0.058 µM) and HER-2 (IC50 = 0.060 µM) with potencies comparable or superior to the standard controls erlotinib and lapatinib, while moderately inhibiting VEGFR-2 (IC50 = 0.51 µM)...SAR analysis highlighted that a 6-methyl substitution on the quinoline core, an unsubstituted N-1 position, and a bulky 3-phenyl group on the thiazole ring are key structural prerequisites for optimal anticancer activity. These findings, along with docking investigation, highlight compound 6b as a promising multi-kinase therapeutic scaffold for further targeted oncological optimization."

Journal • Oncology • CASP3 • CASP7 • EGFR • HER-2

Efficacy and Safety Ranking of HER2-Targeted TKIs in Advanced Breast Cancer: A Bayesian Network Meta-Analysis. (PubMed, Clin Med Insights Oncol) - "Tucatinib combined with trastuzumab and capecitabine (Tucatinib_T_C) demonstrated the highest probability of favorable OS ranking. Regarding safety, pyrotinib combined with trastuzumab and capecitabine (Pyrotinib_T_C) was associated with the highest incidence of serious adverse events, diarrhea, and hand-foot syndrome, whereas Pyrotinib_C showed the highest incidence of anemia and lapatinib plus capecitabine (Lapatinib_C) demonstrated the highest incidence of rash...However, pyrotinib-containing regimens were associated with a higher risk of treatment-related toxicities. These findings highlight the importance of balancing efficacy and safety when selecting HER2-targeted TKI therapies and support individualized treatment strategies for patients with HER2-positive advanced breast cancer."

Journal • Retrospective data • Breast Cancer • Dermatology • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Trastuzumab-TKI combination in HER2-Positive tumors: a FAERS-Based safety profile and multimodal analysis of Tanespimycin's role in enhancing targeting of the HSP90AA1-PI3K-Akt-mTOR axis. (PubMed, Front Pharmacol) - "This study addresses the safety profiles and molecular mechanisms of trastuzumab monotherapy and its combination with lapatinib, neratinib, and tucatinib for treating HER2-positive tumors. This study establishes a novel framework for drug safety evaluation and provides a theoretical rationale for optimizing therapeutic strategies in HER2-positive tumors. These findings highlight the potential advantages of combination therapies regarding AE latency and elucidate the critical role of HSP90AA1."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDC37 • HER-2 • HSP90AA1

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

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

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

Outcomes of patients with small and node-negative HER2-positive early breast cancer treated with adjuvant chemotherapy and anti-HER2 therapy-a sub-analysis of the ALTTO study. (PubMed, Br J Cancer) - P3 | "With most patients treated with anthracycline-based regimens, ALTTO shows that patients with small tumours treated with trastuzumab and concomitant chemotherapy have excellent long-term outcomes, similar to those of the APT trial."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • 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 impact of erythropoiesis-stimulating agents administration concomitantly with adjuvant anti-HER2 treatments on the outcomes of patients with early breast cancer: a sub-analysis of the ALTTO study. (PubMed, Breast Cancer Res Treat) - P3 | "ESA administration to patients receiving adjuvant anti-HER2 treatment for HER2-positive EBC was safe and not associated with a negative impact on survival outcomes."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER

Post-mastectomy radiation therapy in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer: Analysis of the adjuvant lapatinib and/or trastuzumab treatment optimization (ALTTO) trial [BIG 2-06/NCCTG N063D (Alliance)] (ESMO-BC 2025) - "This large and long-term analysis of ALTTO trial shows that LRR events are rare after HER2-directed therapy. PMRT was found to improve loco-regional control and survival outcomes in pts with extended nodal involvement (pN2). With de-escalation of axillary node surgery on the rise, research to guide patient selection for PMRT remains crucial."

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

Ten-year survival of neoadjuvant dual HER2 blockade in patients with HER2-positive breast cancer. (PubMed, Eur J Cancer) - P3 | "Patients with HER2-positive BC showed a durable survival benefit of neoadjuvant anti-HER2, irrespective of treatment arm. Patients who achieve pCR have significantly better outcomes than patients without pCR."

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

Long-term outcomes of dual vs single HER2-directed neoadjuvant therapy in NSABP B-41. (PubMed, Breast Cancer Res Treat) - P3 | "Although pCR, RFI, and OS were numerically better with the dual combination and less with L, the differences were not statistically significant. However, achievement of pCR again correlated with improved outcomes, especially remarkable in the ER-negative subset."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2