PIK3CA

The article discusses the potential of combining radiomic and genomic data to improve thyroid cancer diagnosis and prognosis, highlighting the need for larger studies and standardized methodologies to validate the clinical utility of this approach.

Elacestrant, a selective estrogen receptor degrader, significantly improved progression-free survival (PFS) in ER-positive, HER2-negative, ESR1-mutated metastatic breast cancer patients compared to standard-of-care treatments, particularly for those previously treated with endocrine therapy and CDK4/6i for at least 12 months.

Truqap, the first AKT inhibitor, has arrived in Korea, offering new hope for HR+/HER2- breast cancer patients with PIK3CA, AKT1, and PTEN mutations. Despite its potential, challenges like the domestic diagnostic environment and drug reimbursement limit its impact. Professor Park Kyong-hwa highlights unmet needs in HR+/HER2- treatment, Truqap's clinical benefits, and the importance of genetic analysis for precision medicine.

AstraZeneca's Phase III CAPItello-281 trial showed Truqap (capivasertib) + abiraterone + ADT improved rPFS in PTEN-deficient metastatic hormone-sensitive prostate cancer. Early OS signs also suggest benefit, with ongoing trial for further assessment. Truqap + Faslodex was approved in the EU for ER-positive, HER2-negative advanced breast cancer with PIK3CA, AKT1, or PTEN alterations.

Precision for Medicine and Agena Bioscience's partnership bridges gaps in mutation detection, identifying actionable mutations in 40% of lung tumor samples previously undetected by NGS. The MassARRAY System showed a 2% failure rate vs. 22% with NGS, achieving 100% PPV and 99.7% NPV, significantly advancing diagnostics and offering faster, cost-effective solutions.

Precision for Medicine and Agena Bioscience identified actionable mutations in 40% of lung tumor samples previously failed by NGS, using MassARRAY® technology, presented at AMP 2024.

FDA approved inavolisib with palbociclib and fulvestrant for PIK3CA-mutated, HR-positive, HER2-negative breast cancer, based on INAVO120 study showing improved PFS and ORR. Common adverse reactions include decreased neutrophils and haemoglobin. The treatment is part of Project Orbis, involving international regulatory collaboration.

CDK4/6 inhibitors (ribociclib, abemaciclib, palbociclib) are integrated into HR+/HER2- breast cancer treatment. First-line therapy typically combines a CDK4/6 inhibitor with an AI, with ribociclib preferred due to significant OS improvement in MONALEESA-2. Contraindications include cardiac issues or QTc prolongation for ribociclib, which may lead to abemaciclib or palbociclib use. Post-CDK4/6 inhibitor treatment options include switching inhibitors or adding targeted agents based on mutations. Adjuvant use of abemaciclib and ribociclib has shown reduced recurrence risk in high-risk patients.

Analysis of 19 TN-IBC patients revealed higher BMI, lower germline and somatic mutation burden compared to TN-non-IBC. Germline variants affected RTK-RAS, Hippo, and NOTCH pathways; somatic mutations impacted TP53, GATA3, PIK3CA, CCND1, MAP3K1, and NOTCH1. TN-IBC showed enriched alterations in GATA3, KEAP1, CDKN1B, and PIK3CA. Transcriptomic analysis identified specific gene expression patterns and immune cell fractions, with TN-IBC having higher γδ T cells, M1 macrophages, and eosinophils. Higher mutation load correlated with better response to NAC, suggesting potential targets for enhancing TN-IBC treatment response.

The FDA has approved MI Cancer Seek, a companion diagnostic test using whole exome and transcriptome sequencing to identify cancer patients eligible for targeted therapies, including pan-cancer and tumor-specific indications.