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Published on: July 25, 2020
PIK3CA Mutations in Advanced or Recurrent Endometrial Cancer: An Exploratory Molecular Profiling From the Phase II
Anna Passarelli1, Giovanni Luca Scaglione2, Daniela Califano3
1Uro-Gynecological Medical Oncology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy.
Purpose:
Immunotherapy with chemotherapy significantly improves progression-free survival in advanced endometrial cancer (EC), especially in microsatellite instability-high (MSI-H) cases. Despite this, for recurrent EC in the postimmunotherapy setting, new treatment options are urgently needed. The PI3K pathway is frequently altered in gynecologic cancers, including EC, representing a potential treatment target.
Patients And Methods:
In a preplanned translational analysis of the MITO END-3, we retrospectively analyzed the genomic abnormalities of 107 patients with samples eligible for next-generation sequencing (NGS) analysis (FoundationOne CDx) with a focus on PIK3CA mutational status.
Results:
In our analysis, the four most frequently mutated genes were TP53, PIK3CA, ARID1A, and PTEN. PIK3CA mutations were detected in 51.4% (55/107 patients) of tissue samples. A total of 68 different PIK3CA mutations were observed, of which 64 were considered pathogenic and four were classified as variants of unknown significance, with the co-occurrence of two different pathogenic mutations in 2 patients. The most frequent PIK3CA mutations were found in the kinase domain, most commonly H1047R (11/68) and H1047Y (3/68), and in the helical domain, including E545K (4/68) and E542K (3/68). Notably, 24 different PIK3CA mutations out of 68 reported in MITO END-3 are considered predictive of response to PI3K inhibition with alpelisib according to current literature in breast cancer. Interestingly, PIK3CA mutations were observed in all The Cancer Genome Atlas categories.
Conclusion:
In this post hoc analysis from the MITO END-3 trial, we confirmed the high frequency of PIK3CA mutations in EC, establishing this tumor as an ideal candidate for testing of PI3K inhibitors in clinical trials.
