Phase II Clinical Study of Pyrotinib Combined With Etoposide to Treat HER2-positive Advanced Breast Cancer

2019 ◽  
Author(s):  
Keyword(s):  
Breast Cancer ◽  
Clinical Study ◽  
Advanced Breast Cancer ◽  
Phase Ii ◽  
Advanced Breast ◽  
Her2 Positive ◽  
Phase Ii Clinical Study

PIKHER2: A phase Ib/II study evaluating safety and efficacy of oral BKM120 in combination with lapatinib in HER2-positive, PI3K-activated, trastuzumab-resistant advanced breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS663-TPS663 ◽  
Author(s):  
Anthony Goncalves ◽  
Nicolas Isambert ◽  
Mario Campone ◽  
Veronique Dieras ◽  
Jean Marie Boher ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Phase Ii ◽  
Dose Escalation ◽  
Objective Response ◽  
Mtor Pathway ◽  
Advanced Breast ◽  
Her2 Positive ◽  
Safety And Efficacy ◽  
Phase Ib

TPS663 Background: Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR)-pathway is frequently activated in HER2-positive breast cancer and may play a major role in resistance to trastuzumab. BKM120 is an oral pan-class I PI3K inhibitor with potent and selective activity against wild-type and mutant PI3K p110α. PIKHER2 study will evaluate safety and efficacy of oral, daily lapatinib-BKM120 combination in HER2-positive, trastuzumab-resistant advanced breast cancer (ABC) with activated PI3K/AKT/mTOR pathway. Methods: This open label, single arm, multi-center study includes a phase Ib dose-escalation part and a phase II expansion part at the recommended dose (RP2D). Primary objectives include determination of the maximum-tolerated dose (MTD) of BKM120 in combination with lapatinib in trastumuzab-resistant HER2-positive ABC (phase Ib part) and evaluation of the activity of BKM120-lapatinib combination at RP2D as measured by objective response rate (ORR) in patients with activated PI3K/AKT/mTOR pathway, as defined by PTEN-negative by IHC and/or somatic mutations (exons 9 and 20) of PIK3CA and/or overexpression of phospho-AKT by IHC (phase II part). Secondary objectives include safety and tolerability of the combination, clinical benefit and progression-free survival, pharmacokinetic profiles, biological and pharmacodynamic correlates. Main eligibility criteria are PS ≤ 1, HER2-positive ABC resistant to trastuzumab, documented activated PI3K/AKT/mTOR pathway (phase II part only). A modified CRM using an adaptive Bayesian model guides the dose escalation of both agents with a maximum of 24 patients planned to be enrolled in phase Ib part. Efficacy will be tested according to a standard 2-stage Simon design under the following unacceptable and desirable hypotheses: H0, ORR <= 10% (unacceptable rate) vs. H1, ORR >=30% (desirable rate). A maximum of 35 patients with activated PI3K/AKT/mTOR pathway is planned to be enrolled in phase II part with an interim look after 18 evaluable patients will have been recruited. Clinical trial information: NCT01589861.

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

2020 ◽  
Vol 26 (22) ◽  
pp. 5820-5829 ◽  
Author(s):  
Eva Ciruelos ◽  
Patricia Villagrasa ◽  
Tomás Pascual ◽  
Mafalda Oliveira ◽  
Sonia Pernas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Phase Ii ◽  
Advanced Breast ◽  
Her2 Positive

scholarly journals Current and future landscape of targeted therapy in HER2-positive advanced breast cancer: redrawing the lines

2022 ◽  
Vol 14 ◽  
pp. 175883592110666
Author(s):  
Christine Simmons ◽  
Daniel Rayson ◽  
Anil Abraham Joy ◽  
Jan-Willem Henning ◽  
Julie Lemieux ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Phase Ii ◽  
Advanced Breast ◽  
Phase Iii ◽  
Second Line ◽  
Her2 Positive ◽  
Line Therapy ◽  
Phase Iii Trials ◽  
Third Line

Background: Evidence to date supports continued human epidermal growth factor receptor 2 (HER2) suppression beyond progression on HER2-directed therapy for advanced HER2-positive breast cancer. Data from several phase II and III trials evaluating HER2-directed therapy following second-line T-DM1 have recently become available. Methods: We performed a systematic search of the published and presented literature to identify phase II and phase III trials assessing novel HER2-targeted agents as third-line therapy or beyond for HER2-positive advanced breast cancer using search terms ‘breast cancer’ AND ‘HER2’ AND ‘advanced’ AND (‘phase II’ OR ‘phase III’). Results: Eight clinical trials reporting efficacy outcomes on third-line or greater HER2-directed therapy for HER2-positive advanced breast cancer were identified. In phase III trials, margetuximab and neratinib combinations demonstrated significant 1.3-month (hazard ratio, HR = 0.71, p < 0.001) and 0.1-month (HR = 0.76, p = 0.006) net improvements in median progression-free survival (PFS), respectively, with no significant improvements in overall survival (OS). Tucatinib added to trastuzumab and capecitabine demonstrated a significant 2.7-month improvement in median PFS (HR = 0.57, p < 0.00001) and a 5.5-month improvement in median OS (HR = 0.73, p = 0.004) in a randomized phase II trial, including significant clinical benefit for patients with brain metastases. Finally, trastuzumab-deruxtecan, zenocutuzumab, and poziotinib demonstrated benefit in phase II trials with the most robust overall response rate (62.0%) and median duration of response (18.2 months) observed for trastuzumab-deruxtecan among heavily pretreated patients. Conclusion: Tucatinib plus trastuzumab and capecitabine significantly prolongs OS, and promising preliminary response outcomes for trastuzumab-deruxtecan suggest that sequencing of these regimens following second-line therapy is reasonable.

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