Studieoverzicht - 2022-03 ALPHABET

International, multicenter, open-label, controlled phase III randomized clinical trial

To determine whether the PI3K inhibitor alpelisib + trastuzumab improve efficacy, as measured by PFS, compared to trastuzumab + chemotherapy of physician's choice (vinorelbine, capecitabine or eribulin) in previously treated HER2+/HR-PIK3CA mutated advanced breast cancer patients.

To determine whether the PI3K inhibitor alpelisib + trastuzumab + fulvestrant improve efficacy, as measured by PFS, compared to trastuzumab + chemotherapy of physician's choice (vinorelbine, capecitabine or eribulin) in previously treated HER2+/HR+ PIK3CA mutated advanced breast cancer patients.

• Progression Free Survival (PFS) 
• Overall Survival (OS) 
• Objective Response (OR)
• Safety and tolerability

• Documented HER2+ status based on local laboratory determination, preferably on the most recent available FFPE tumor sample, and according to American Society of ClinicalOncology (ASCO)/College of American Pathologists (CAP) international guidelines valid at the time of the assay.
• Documented HR status based on local laboratory, preferably on the most recent available FFPE tumor sample, and according to ASCO/CAP international guidelines valid at the time of the assay. In case of discordance in HR status by different biopsies, we will consider the most recent one. HR+ will be defined as ≥1% positive cells by immunohistochemistry for Estrogen Receptor (ER) and/or Progesterone Receptor (PgR). HR- will be defined as <1% positive cells by immunohistochemistry for both ER and PgR. Considering that there are limited data on endocrine therapy benefit for cancers with 1% to 10% of cells staining ER positive, for the purpose of this study, patients with ER and PgR expression between 1 and 10% (considered to be HR low by the most recent ASCO/CAP guidelines) will be eligible for inclusion in the HR- cohort.
• Patients with a PIK3CA tumor mutation at central laboratory determination, preferably on the most recent available FFPE tumor sample.
• At least 1 but no more than 4 prior lines of anti-HER2 based therapy for metastatic breast cancer (MBC). Maintenance therapy will not count as an additional line of therapy.
• At least 1 prior line of trastuzumab in the metastatic setting, or in the (neo)adjuvant setting (provided the patient relapsed while on therapy or within 6 months after completing adjuvant trastuzumab)

Centra open voor inclusie:

• VieCuri Medisch Centrum, Venlo
• Radboudumc, Nijmegen
• Admiraal de Ruyter Ziekenhuis, Goes
• Meander Medisch Centrum, Amersfoort

5 andere centra zijn momenteel in opstart voor deze studie.