Palbociclib and trastuzumab for HER2-positive metastatic breast cancer: final overall survival results of cohort A and B of SOLTI-1303-PATRICIA trial.

Background: The SOLTI-1303-PATRICIA trial (NCT02448420) is a phase II study investigating palbociclib and trastuzumab, with or without endocrine therapy, in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). This manuscript presents final overall survival (OS) results and biomarker analyses.

Patients And Methods: Patients previously treated with trastuzumab and two to four regimens were eligible.

Zanidatamab plus palbociclib and fulvestrant in previously treated patients with hormone receptor-positive, HER2-positive metastatic breast cancer: primary results from a two-part, multicentre, single-arm, phase 2a study.

Background: New HER2-targeted regimens, including chemotherapy-free options, are needed for metastatic breast cancer. In an ongoing, two-part, phase 2a study, we assessed the safety and antitumour activity of zanidatamab, a HER2-targeted bispecific antibody, plus palbociclib and fulvestrant, in heavily pretreated patients with hormone receptor-positive, HER2-positive advanced or metastatic breast cancer.

Methods: This multicentre, single-arm, two-part, phase 2a study is being conducted at 13 university hospitals, cancer centres, or research institutes in Spain, Canada, and the USA.

Generation of chimeric antigen receptor T cells targeting p95HER2 in solid tumors.

The redirection of T lymphocytes against tumor-associated or tumor-specific antigens, using bispecific antibodies or chimeric antigen receptors (CAR), has shown therapeutic success against certain hematological malignancies. However, this strategy has not been effective against solid tumors. Here, we describe the development of CAR T cells targeting p95HER2, a tumor-specific antigen found in HER2-amplified solid tumors.

Trastuzumab Duocarmazine in Pretreated Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Breast Cancer: An Open-Label, Randomized, Phase III Trial (TULIP).

Purpose: Human epidermal growth factor receptor 2 (HER2)-targeted therapy is standard of care for HER2-positive (HER2+) breast cancer, but most patients develop progressive disease with persistent HER2 expression. No definitive treatment guidance currently exists beyond second line. Trastuzumab duocarmazine (T-Duo) is a third-generation, HER2-targeted antibody-drug conjugate that demonstrated efficacy and acceptable safety in phase I studies of heavily pretreated patients with HER2+/HER2-low breast cancer.

Clinicopathological and molecular predictors of [F]FDG-PET disease detection in HER2-positive early breast cancer: RESPONSE, a substudy of the randomized PHERGain trial.

Background: The PHERGain study (NCT03161353) is assessing early metabolic responses to neoadjuvant treatment with trastuzumab-pertuzumab and chemotherapy de-escalation using a [Fluorine]fluorodeoxyglucose-positron emission tomography ([F]FDG-PET) and a pathological complete response-adapted strategy in HER2-positive (HER2+) early breast cancer (EBC). Herein, we present RESPONSE, a PHERGain substudy, where clinicopathological and molecular predictors of [F]FDG-PET disease detection were evaluated.

Methods: A total of 500 patients with HER2 + EBC screened in the PHERGain trial with a tumor size > 1.

3-year invasive disease-free survival with chemotherapy de-escalation using an F-FDG-PET-based, pathological complete response-adapted strategy in HER2-positive early breast cancer (PHERGain): a randomised, open-label, phase 2 trial.

Background: PHERGain was designed to assess the feasibility, safety, and efficacy of a chemotherapy-free treatment based on a dual human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab and pertuzumab in patients with HER2-positive early breast cancer (EBC). It used an fluorine-fluorodeoxyglucose-PET-based, pathological complete response (pCR)-adapted strategy.

Methods: PHERGain was a randomised, open-label, phase 2 trial that took place in 45 hospitals in seven European countries.

Optimal [F]FDG PET/CT Cutoff for Pathologic Complete Response in HER2-Positive Early Breast Cancer Patients Treated with Neoadjuvant Trastuzumab and Pertuzumab in the PHERGain Trial.

The PHERGain trial investigated the potential of metabolic imaging to identify candidates for chemotherapy deescalation in human epidermal growth factor receptor 2 (HER2)-positive, invasive, operable breast cancer with at least 1 breast lesion evaluable by [F]FDG PET/CT. [F]FDG PET/CT responders were defined as patients with an SUV reduction (ΔSUV) of at least 40% in all of their target lesions after 2 cycles of trastuzumab and pertuzumab (HP) (with or without endocrine therapy). In total, 227 of 285 patients (80%) included in the HP arm showed a predefined metabolic response and received a total of 8 cycles of HP (with or without endocrine therapy).

Real world data on the demographic and clinicopathological profile and management of patients with early-stage HER2-positive breast cancer and residual disease treated with adjuvant trastuzumab emtansine (KARMA study).

Introduction: Trastuzumab emtansine (T-DM1) significantly improves invasive disease-free survival and reduces the risk of recurrence in patients with HER2-positive early breast cancer (EBC) with residual disease (RD). The KARMA study aimed to describe the characteristics and management of these patients in clinical practice in Spain.

Material And Methods: We conducted a multicentre retrospective study in patients with HER2-positive EBC with RD following neoadjuvant treatment (NeoT) and who had received ≥1 dose of T-DM1 as adjuvant treatment.

The change of paradigm in the treatment of HER2-positive breast cancer with the development of new generation antibody-drug conjugates.

HER2-positive breast cancer is an aggressive disease. As a result of the development of specific HER2-targeted therapies, such as trastuzumab, more than 20 years ago, the prognosis of these patients has improved. Metastatic HER2-positive breast cancer patients are achieving better survival rates upon treatment with anti-HER2 therapies than patients with HER2-negative disease.

Systemic Therapy for HER2-Positive Metastatic Breast Cancer: Current and Future Trends.

Approximately 20% of breast cancers (BC) overexpress human epidermal growth factor receptor 2 (HER2). This subtype of BC is a clinically and biologically heterogeneous disease that was associated with an increased risk for the development of systemic and brain metastases and poor overall survival before anti-HER2 therapies were developed. The standard of care was dual blockade with trastuzumab and pertuzumab as first-line followed by TDM-1 as second-line.

Clearance of ctDNA in triple-negative and HER2-positive breast cancer patients during neoadjuvant treatment is correlated with pathologic complete response.

Background: Although the standard of care is to perform surgery of primary breast cancer (BC) after neoadjuvant chemotherapy (NAC), for certain patients achieving clinical complete response (cCR) and pathologic complete response (pCR), omission of surgical treatment may be an option. Levels of circulating tumor DNA (ctDNA) during and after therapy could identify patients achieving minimal residual disease. In this study, we evaluated whether ctDNA clearance during NAC could be a correlate to effective response in human epidermal growth factor receptor 2 positive (HER2+) and triple-negative (TN) BC patients.

Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial.

JCO Final overall survival (OS) in SOPHIA (ClinicalTrials.gov identifier: NCT02492711), a study of margetuximab versus trastuzumab, both with chemotherapy, in patients with previously treated human epidermal growth factor receptor 2-positive advanced breast cancer, is reported with updated safety. Overall, 536 patients in the intention-to-treat population were randomly assigned to margetuximab (15 mg/kg intravenously once every 3 weeks; n = 266) plus chemotherapy or trastuzumab (6 mg/kg intravenously once every 3 weeks after a loading dose of 8 mg/kg; n = 270) plus chemotherapy.

Therapy-Induced Senescence Enhances the Efficacy of HER2-Targeted Antibody-Drug Conjugates in Breast Cancer.

Unlabelled: Antibody-drug conjugates (ADC) are antineoplastic agents recently introduced into the antitumor arsenal. T-DM1, a trastuzumab-based ADC that relies on lysosomal processing to release the payload, is approved for HER2-positive breast cancer. Next-generation ADCs targeting HER2, such as [vic-]trastuzumab duocarmazine (SYD985), bear linkers cleavable by lysosomal proteases and membrane-permeable drugs, mediating a bystander effect by which neighboring antigen-negative cells are eliminated.

Chemotherapy de-escalation using an F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain): a multicentre, randomised, open-label, non-comparative, phase 2 trial.

Background: Several de-escalation approaches are under investigation in patients with HER2-positive, early-stage breast cancer. We assessed early metabolic responses to neoadjuvant trastuzumab and pertuzumab using F-fluorodeoxyglucose (F-FDG)-PET (F-FDG-PET) and the possibility of chemotherapy de-escalation using a pathological response-adapted strategy.

Methods: We did a multicentre, randomised, open-label, non-comparative, phase 2 trial in 45 hospitals in Spain, France, Belgium, Germany, the UK, Italy, and Portugal.

Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial.

Importance: ERRB2 (formerly HER2)-positive advanced breast cancer (ABC) remains typically incurable with optimal treatment undefined in later lines of therapy. The chimeric antibody margetuximab shares ERBB2 specificity with trastuzumab but incorporates an engineered Fc region to increase immune activation.

Objective: To compare the clinical efficacy of margetuximab vs trastuzumab, each with chemotherapy, in patients with pretreated ERBB2-positive ABC.

Trastuzumab Emtansine Plus Non-Pegylated Liposomal Doxorubicin in HER2-Positive Metastatic Breast Cancer (Thelma): A Single-Arm, Multicenter, Phase Ib Trial.

The paper assesses the dose-limiting toxicities and the maximum tolerated dose (MTD) of trastuzumab emtansine (T-DM1) combined with non-pegylated liposomal doxorubicin (NPLD) in HER2-positive (HER2+) metastatic breast cancer (MBC). This single-arm, open-label, phase Ib trial (NCT02562378) enrolled anthracycline-naïve HER2+ MBC patients who had progressed on trastuzumab and taxanes. Patients received a maximum of 6 cycles of NPLD intravenously (IV) at various dose levels (45, 50, and 60 mg/m) in the "3 plus 3" dose-escalation part.

Palbociclib and Trastuzumab in HER2-Positive Advanced Breast Cancer: Results from the Phase II SOLTI-1303 PATRICIA Trial.

Purpose: To assess palbociclib in combination with trastuzumab with or without endocrine therapy in patients with HER2-positive advanced breast cancer.

Patients And Methods: PATRICIA is a prospective, open-label, multicenter phase II trial. Patients had received 2-4 prior lines of anti-HER2-based regimens.

Neratinib plus capecitabine for the treatment of advanced HER2-positive breast cancer.

Introduction: Several agents are being developed for advanced HER2-positive breast cancer, such as potent tyrosine kinase inhibitors (TKI) targeting ErbB family receptors, novel antibody-drug conjugates, higher affinity anti-HER2 antibodies, among others. Neratinib is an irreversible pan-HER (EGFR, ERBB2, and ERBB4) TKI being tested in early and advanced HER2-positive breast cancer. In the NALA trial, neratinib plus capecitabine led to increased PFS and time to intervention for central nervous system disease over the standard regimen of lapatinib plus capecitabine.

Paraneoplastic cerebellar degeneration diagnosed by anti-Yo determination in a young woman with early breast cancer.

A 44-year-old woman diagnosed with a HER2 positive early breast cancer, receiving neoadjuvant treatment with paclitaxel and targeted agents, trastuzumab together with pertuzumab, presented to the emergency room with gait instability and upper right limb weakness. The neurological examination was compatible with cerebellar alteration showing right dissymmetry of the finger-nose and heel-knee manoeuvre. A head CT and a brain MRI were performed and negative.

The Second Generation Antibody-Drug Conjugate SYD985 Overcomes Resistances to T-DM1.

Trastuzumab-emtansine (T-DM1) is an antibody-drug conjugate (ADC) approved for the treatment of HER2 (human epidermal growth factor receptor 2)-positive breast cancer. T-DM1 consists of trastuzumab covalently linked to the cytotoxic maytansinoid DM1 via a non-cleavable linker. Despite its efficacy, primary or acquired resistance frequently develops, particularly in advanced stages of the disease.

Palbociclib and ribociclib in breast cancer: consensus workshop on the management of concomitant medication.

Drug-drug interactions are of significant concern in clinical practice in oncology, particularly in patients receiving Cyclin-dependent kinase (CDK) 4/6 inhibitors, which are typically exposed to long-term regimens. This article presents the highlights from the 'First Workshop on Pharmacology and Management of CDK4/6 Inhibitors: Consensus about Concomitant Medications'. The article is structured into two modules.

Neoadjuvant Model as a Platform for Research in Breast Cancer and Novel Targets under Development in this Field.

For decades, the neoadjuvant setting has provided a useful scenario for research in breast cancer. Historically, neoadjuvant clinical trials, either hormone therapy-based or chemotherapy-based, have tried to recapitulate the results of their counterpart adjuvant studies, but with smaller patient numbers, more rapid outcomes (clinical response and/or pathologic complete response (pCR)), together with additional biologic information. As for neoadjuvant chemotherapy trials, the increase in pCR rates has been recently accepted as an appropriate surrogate marker to accelerate drug approval in high-risk breast cancer patients.