Pertuzumab

About: Pertuzumab is a research topic. Over the lifetime, 1453 publications have been published within this topic receiving 73219 citations. The topic is also known as: 2C4 Antibody & MOAB 2C4.

Abstract OT1-07-04: [Fam-] trastuzumab deruxtecan (T-DXd; DS-8201a) vs investigator’s choice of treatment in subjects with HER2-positive, unresectable and/or metastatic breast cancer who previously received T-DM1: A randomized, phase 3 trial (DESTINY-Breast02)

Abstract: Background: There is no uniform standard of care for HER2-positive breast cancer (BC) after disease progression on ado-trastuzumab emtansine (T-DM1). [Fam-] trastuzumab deruxtecan (T-DXd; formerly DS-8201a) is a novel HER2-targeted antibody-drug conjugate (ADC) with a humanized HER2 antibody attached to a topoisomerase I inhibitor payload by a cleavable tetrapeptide-based linker and a drug-to-antibody ratio of 7 to 8. It was designed with the goal of improving critical attributes of an ADC. In a phase 1 study, T-DXd showed promising antitumor activity in subjects with HER2-positive BC previously treated with T-DM1 with a confirmed objective response rate (ORR) of 59.5% (Tamura et al, Lancet Oncol, 2019). Results from the pivotal, phase 2 study of subjects with HER2-positive BC previously treated with T-DM1 (DESTINY-Breast01) confirmed the activity observed in the phase 1 study and will be presented at the meeting (Krop, et al). Here, we describe the phase 3 confirmatory trial evaluating T-DXd in subjects with HER2-positive, unresectable and/or metastatic breast cancer who previously received T-DM1. Study Description: DESTINY-Breast02 is a multicenter, open-label, phase 3 trial that is comparing the efficacy and safety of T-DXd with those of the investigator’s choice of therapy in subjects with centrally confirmed, HER2-positive (IHC 3+ or ISH+), unresectable and/or metastatic BC that progressed on or after T-DM1. The trial started in August 2018 and is recruiting subjects from ≈ 190 sites in North and South America, Europe, and Asia. Approximately 600 subjects will be randomized (2:1) to T-DXd or the investigator’s choice of treatment (trastuzumab + capecitabine or lapatinib + capecitabine). Randomization is stratified by hormone receptor status, prior pertuzumab treatment, and history of visceral disease. T-DXd (5.4 mg/kg) will be administered intravenously once every 3 weeks. Progression-free survival (PFS) based on blinded, independent central review using RECIST v1.1 criteria is the primary efficacy endpoint; overall survival (OS) is the key secondary endpoint. Other secondary efficacy endpoints are ORR, duration of response, and PFS based on investigator assessment. Safety assessments include serious and treatment-emergent adverse events, physical examinations, vital signs, and clinical laboratory parameters. Health-related quality of life will also be measured. Long-term follow-up will continue after the primary analysis every 3 months until death, withdrawal of consent, loss to follow-up, or trial closure. Efficacy analyses will include all randomized subjects, and safety analyses will include all randomized subjects who received ≥ 1 dose of trial treatment. For further information on this trial, visit ClinicalTrials.gov (NCT03523585). Citation Format: Fabrice Andre, Javad Shahidi, Caleb Lee, Kongming Wang, Ian E Krop. [Fam-] trastuzumab deruxtecan (T-DXd; DS-8201a) vs investigator’s choice of treatment in subjects with HER2-positive, unresectable and/or metastatic breast cancer who previously received T-DM1: A randomized, phase 3 trial (DESTINY-Breast02) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-07-04.

Clinical benefit of treatment after trastuzumab emtansine for HER2-positive metastatic breast cancer: a real-world multi-centre cohort study in Japan (WJOG12519B)

Abstract: Trastuzumab emtansine (T-DM1) treatment for human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer after taxane with trastuzumab and pertuzumab is standard therapy. However, treatment strategies beyond T-DM1 are still in development with insufficient evidence of their effectiveness. Here, we aimed to evaluate real-world treatment choice and efficacy of treatments after T-DM1 for HER2-positive metastatic breast cancer. In this multi-centre retrospective cohort study involving 17 hospitals, 325 female HER2-positive metastatic breast cancer patients whose post-T-DM1 treatment began between April 15, 2014 and December 31, 2018 were enrolled. The primary end point was the objective response rate (ORR) of post-T-DM1 treatments. Secondary end points included disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), and overall survival (OS). The median number of prior treatments of post-T-DM1 treatment was four. The types of post-T-DM1 treatments included (1) chemotherapy in combination with trastuzumab and pertuzumab (n = 102; 31.4%), (2) chemotherapy concomitant with trastuzumab (n = 78; 24.0%), (3), lapatinib with capecitabine (n = 63; 19.4%), and (4) others (n = 82; 25.2%). ORR was 22.8% [95% confidence interval (CI): 18.1–28.0], DCR = 66.6% (95% CI 60.8–72.0), median PFS = 6.1 months (95% CI 5.3–6.7), median TTF = 5.1 months (95% CI 4.4–5.6), and median OS = 23.7 months (95% CI 20.7–27.4). The benefits of treatments after T-DM1 are limited. Further investigation of new treatment strategies beyond T-DM1 is awaited for HER2-positive metastatic breast cancer patients.

Recent advances in the treatment of hormone receptor-positive/human epidermal growth factor 2-positive advanced breast cancer

Abstract: Hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-positive (HR+/HER2+) advanced breast cancer is a special subtype of cancer with unique features. Major guidelines recommend that combination therapy containing anti-HER2 therapy (e.g., trastuzumab and pertuzumab) should be applied as the first-line treatment for HER2+ advanced breast cancer, regardless of HR status. Endocrine therapy could be relegated to patients who cannot tolerate chemotherapy or as a post-chemotherapy empirical maintenance strategy. Previous studies have shown that the HR pathway interacts with the HER2 pathway, and the HR and HER2 pathways of endocrine therapy combined with targeted therapy can effectively avoid tumor resistance. Therefore, the combination of endocrine and targeted therapies is the preferred treatment plan for HR+/HER2+ patients to replace chemotherapy. In this review, we will discuss research progress regarding endocrine therapy combined with anti-HER2 therapy in patients with advanced breast cancer, to provide more evidence for clinical practice and broader perspectives for related research. In the future, we hope there will be more studies on HR+/HER2+ advanced breast cancer to elucidate the optimal and appropriate treatment for these patients.

Efficacy of trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (MBC) previously treated with pertuzumab (P).

Abstract: 1023Background: T-DM1 was approved for pts with HER2+ MBC previously treated with trastuzumab (H) and a taxane based on the phase III EMILIA study. P in combination with H + docetaxel (T) later became the first-line standard of care for HER2+ MBC, but there are limited data on T-DM1 efficacy in pts who previously received P. We present exploratory efficacy results from pts treated with T-DM1 any time after P from 2 phase III studies: CLEOPATRA and PHEREXA. Methods: CLEOPATRA (NCT00567190) and PHEREXA (NCT01026142) are randomized, 2-arm trials evaluating P-based regimens for HER2+ MBC. CLEOPATRA studies H + T + P vs HT + placebo in pts with no prior anti-HER2 treatment (tx) or chemotherapy for MBC, while PHEREXA studies H + capecitabine (C) +/− P in pts who progressed during/after previous H tx for MBC. We assessed overall survival (OS) in an exploratory analysis of pts who either received or did not receive T-DM1 at any time after discontinuing study-assigned tx in CLEOPATRA or PHEREXA. Results: Of 408 pt...

Trastuzumab and pertuzumab combination therapy for advanced pre-treated HER2 exon 20-mutated non-small cell lung cancer.

Abstract: In 1-3% of non-small cell lung cancer (NSCLC) human epidermal growth factor 2 (HER2) mutations are identified as a genomic driver. Nevertheless, no HER2-targeted treatment is approved for NSCLC. In the Drug Rediscovery Protocol (DRUP), patients are treated with off-label drugs based on their molecular profile. Here, we present the results of the cohort 'trastuzumab/pertuzumab for HER2 exon20 mutation positive (HER2m+) NSCLC'.Patients with treatment refractory, advanced HER2m+ NSCLC with measurable disease (RECISTv1.1) were eligible. Treatment with intravenous trastuzumab combined with pertuzumab every 3 weeks was administered. The primary end-point was clinical benefit (CB: either objective response or stable disease ≥ 16 weeks). Patients were enrolled using a Simon-like 2-stage design, with 8 patients in stage 1 and up to 24 patients in stage 2 if at least 1 patient had CB in stage 1. At baseline, a biopsy for biomarker analysis, including whole genome sequencing, was obtained.Twenty-four evaluable patients were enrolled and treated between May 2017 and August 2020. CB was observed in 9 patients (38%); including an objective response rate of 8.3% (2 patients had a partial response) and 7 patients with stable disease ≥ 16 weeks. The most frequently observed HER2 mutation was p.Y772_A775dup (71%, n = 20). Median follow-up was 13 months, median progression-free survival and overall survival 4 (95% CI 3-6) and 10 months (95% CI 4 - not reached), respectively. Whole genome sequencing data (available for 67% of patients) confirmed the inclusion mutation in all cases. No unexpected toxicity was observed.Despite the fact that the study did meet its primary end-point, trastuzumab/pertuzumab was only marginally active in a subset of patients with heavily pre-treated HER2m+ NSCLC.