Abstract OT1-1-12: NSABP FB-7 Trial: A Phase II Randomized Clinical Trial Evaluating Neoadjuvant Therapy Regimens with Weekly Paclitaxel and Neratinib or Trastuzumab or Neratinib and Trastuzumab Followed by Doxorubicin and Cyclophosphamide with Postoperative Trastuzumab in Women with Locally Advanced HER2-Positive Breast Cancer

Author(s):  
J Lu ◽  
SA Jacobs ◽  
ME Buyse ◽  
S Paik ◽  
N Wolmark
2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS1102-TPS1102
Author(s):  
Patricia LoRusso ◽  
Mary Josephine Paula Pilat ◽  
Cesar Augusto Santa-Maria ◽  
Roisin M. Connolly ◽  
Erin Elizabeth Roesch ◽  
...  

TPS1102 Background: While immunostimulatory therapies have shown great success, a major challenge remains identification of mechanisms to effectively treat the majority of patients with so-called "non-inflamed" tumors lacking marked lymphocyte infiltration and PD-L1 expression. The DNA repair proficiency of a tumor may impact its potential for immune recognition and sensitivity to immune checkpoint blockade. Preclinically, PARP inhibition in HDR-deficient tumors has been shown to trigger antitumor immunity through a STING-dependent antitumor immune response. Effects of PARP inhibitors were augmented when combined with PD-1 blockade. We hypothesize that enhanced DNA damage and cell death induced by PARP inhibition in tumors with homology directed repair (HDR) deficiency will enhance adaptive anti-tumor immune responses and increase sensitivity to PD-1 axis blockers. Methods: This is a randomized, open-label phase II clinical trial exploring the PARP inhibitor olaparib either alone or in combination with the anti-PD-L1 human monoclonal antibody atezolizumab in BRCA1/2 mutated locally advanced or metastatic non-HER2-positive breast cancer. HDR deficiency is defined as the presence of deleterious BRCA 1/2 mutations. Randomization occurs in a 1:1 fashion to two arms: (1) olaparib 300 mg PO bid continuously in 21-day cycles or (2) olaparib 300 mg PO bid continuously in combination with atezolizumab 1200 IV every 3 weeks in 21-day cycles. Patients undergo baseline evaluations and pre-treatment biopsy within 2 weeks of starting therapy. Repeat biopsies are required at the time of first tumor assessment scan (6 weeks from the start of treatment) and in the event of disease progression. Correlative studies, including detailed analysis of the genomic profile and tumor immune contexture, will be performed at each biopsy time point. The primary objective is to compare progression free survival between the study arms. If progression occurs on the olaparib monotherapy arm, cross-over to the combination arm is allowed. This study began enrolling in August 2018; 47 of the planned 72 patients have been registered. Clinical trial information: NCT02849496 .


2021 ◽  
pp. 68-74
Author(s):  
E. V. Lubennikova ◽  
Ya. V. Vishnevskaya

The widespread introduction of anti-HER2 agents has changed the natural course of Her2-positive breast cancer. The use of trastuzumab, and later dual anti-HER2 blockade with pertuzumab, in neoadjuvant regimens significantly increased the chances of complete cure. However, among patients with early and locally advanced forms of Her2-positive cancer, there is a cohort with an extremely unfavorable prognosis – tumors that have not achieved complete pathomorphological regression after neoadjuvant chemotherapy.The presence of a residual tumor in Her2-positive breast cancer has long been only a prognostically unfavorable factor without the potential to influence disease outcome. The results of the international phase III study KATHERINE, which demonstrated the high efficacy of post-adjuvant therapy with trastuzumab emtansine (T-DM1) in this patient cohort, have established a new standard of care. Due to T-DM1 adjuvant therapy, the possibility to significantly improve long-term results determined the predictive characteristics of the morphological response to the choice of treatment tactics, which became an important argument in favor of neoadjuvant therapy in patients with not only locally advanced but also primarily resectable Her2-positive breast cancer, followed by personalization of therapy.This article presents our own experience with post-neoadjuvant therapy with trastuzumab emtansine in a young patient with a residual tumor. The data of the main studies in early Her2-positive breast cancer are summarized.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 602-602
Author(s):  
Maria Fernandez Abad ◽  
Isabel Calvo ◽  
Noelia Martinez ◽  
Mercedes Herrero ◽  
Yolanda Quijano ◽  
...  

602 Background: B in combination with T has showed meaningful activity in patients (pts) with metastatic HER2-positive breast cancer. AVANTHER is a Phase II trial of preoperative systemic therapy combining B with T and P in a weekly regimen in HER2 positive breast cancer to assess safety and efficacy of the combination. Methods: Pts with centrally-confirmed HER2-positive (IHC 3+ or FISH positive) breast cancer (stage II or III including locally advanced) received neoadjuvant chemotherapy (NC) with weekly P (80mg/m2/week) for 12 weeks in combination with weekly T (4mg/kg loading dose and 2 mg/kg maintenance) and B (15mg/kg every 3 weeks) for 4 cycles. After surgery all pts received T (1 year) and liposomal doxorubicin plus cyclophosphamide every 3 weeks (4 cycles); primary endpoint was rate of pathological complete response (pCR) in breast and axilla. For all patients, a tissue sample at baseline as well as at surgery was collected for biomarker analyses. Results: A total of 44 pts have been enrolled. Median tumor size: 3.9 cm. Seven (19.4%) pts had stage IIA; 17 (47.2%) stage IIB; 8 (22.2%) stage IIIA and 4 (11.1%) stage IIIB. Twenty-one (58.3%) pts had both positive-hormonal receptors and 10 (27.8%) were hormone receptor negative. Eight (22.2%) pts had sentinel biopsy before NC, being negative in 6 (16.7%) cases. Data from surgery (only from 36 pts): pCR was achieved in 16 (44.4%) pts. Safety and tolerability were good, with rare adverse events of grade ≥3 [1 (2.8%) episode of severe hypertension]. Conclusions: These data show that the combination of P with T and B without an anthracycline for 12 weeks is very effective as NC in HER2 positive breast cancer pts with a high rate of pCR and minimal side effects.


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