PIK3CA Q546

The frequent alterations of the PI3K pathway in gynecological cancers could emerge as new treatment target. Our data confirm the high frequency of PIK3CA mutations establishing EC as an ideal candidate for testing of PI3K inhibitors regardless of the TCGA classification. Moreover, these data confirm that other targetable mutations are present also in MSS EC group thus suggesting that new target agents should be explored.

However, clinical trials have been predominantly carried out with selected populations and single drugs (Palbociclib, Ribociclib or Abemaciclib). At baseline, and considering the pre-defined criteria, ctDNA analysis detected PIK3CA mutations in 32.25% and 44.44% of patients by AVENIO and ddPCR, respectively. ESR1 mutations were detected in 3.22% and 9.37% by AVENIO and ddPCR, respectively. For PIK3CA mutations, the Kappa value was 0.62 (p-value: 0.0004) and 0.47 for ESR1 mutations (p-value: 0.0039).

P2, N=51, Recruiting, GOG Foundation | Not yet recruiting --> Recruiting

Our study shows the frequency of PIK3CAm and distribution of exons 9 and 20 are similar to those found previously in the literature by Tan (Xie) et al., 2022. Our results demonstrate PIK3CA having a low frequency of MSI-H co-occurrence, higher TMB scores, and increased co-occurring alterations with notable increased in APC, BRAF, EGFR, ERBB2 and KRAS, which may suggest higher genomic instability. Our findings underscore the clinical significance of PIK3CAm in the context of CRC, emphasizing their role as key drivers of oncogenesis, and supports the development of tailored therapeutic strategies such as combining PIK3CAi with immunotherapy or other targeted therapies.

Table: 439P PIK3CA mutation results of HeSMO's program Conclusions In our series, 40.94% of the patients tested, were detected with mutations in PIK3CA gene, in accordance with published data. Apart from the significant implications for treatment possibilities in a substantial patients' population, these results provide valuable epidemiological data and strengthen our efforts for reimbursement of PIK3CA mutation testing in Greece.

Taken together, our work provided a comprehensive analysis of driver and targetable alterations in SBA, which can facilitate the practice of precision oncology in this challenging disease.

In this group of HR/HER2 breast cancer patients, common PIK3CA gene mutations account for the vast majority of the mutations. New rare variants in PIK3CA are also identified while their clinical significance needs to be further studied in a large cohort and/or multi-center study.

A smaller fraction of H1047R in blood compared to a tumor indicates its low copy number in circulation. Thus H1047R mutation can be used as a predictive pCR and the development of a specific inhibitor against this mutation may be useful in the fight against this breast cancer subtype.

PIK3CA mutation assays are intended for use as a companion diagnostic test, to aid clinicians in the identification of breast cancer patients who may be eligible for treatment with alpelisib, an alpha-specific PIK3CA inhibitor, based on a PIK3CA mutation detected result... Screening for PIK3CA mutations highlighted the highly diverse mutational status of this gene among breast cancer patients. As the mutational profile of a patient renders them eligible for targeted therapy, an urgent need arises to perform comprehensive next-generation sequencing assays to detect additional hotspot and non-hotspot mutations.

P1/2, N=6, Terminated, David VanderWeele | Trial completion date: Dec 2024 --> Aug 2022 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2023 --> Aug 2022; Funder Decision