Abstract 5450
Background
Perivascular epithelioid cell tumors (PEComa) are exceedingly rare mesenchymal neoplasms arising in a variety of anatomic sites. mTOR inhibitors are active in these neoplasms. However, no other effective treatments are available in those patients progressing to them. The PI3K–Akt–mTOR signaling pathway modulates neoplastic growth through signaling activation of ER and the EGF receptor family of receptor tyrosine kinases. ER drives PI3K/AKT activation in response to mTORC1 inhibition. This provides a rationale for combining anti-estrogens and mTORC1 inhibitors.
Methods
We retrospectively identified patients with advanced PEComa treated with mTOR inhibitors since January 2002 at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan – Italy. In a subgroup of them, exemestane was added at the time of progression.
Results
Twenty-eight patients with advanced PEComa treated with mTOR inhibitors were identified. Twenty–six were evaluable for response. Twelve out 26 (46%) had a PR and seven (27%) a SD, with a median PFS of 7 months. At the time of progression to sirolimus, 5 patients received a combination of sirolimus and exemestane and one of sirolimus, exemestane and GnRH. Three patients out 6 had a PR, 2 out 6 had a SD, and 1 out 6 had a PD, with a median PFS of 6 months. In this subgroup of patients treated with the combination, previous PFS to mTOR inhibitors was 6.6 months.
Conclusions
In this small retrospective series, the combination of mTOR inhibitors and exemestane obtained a reversion of resistance to mTOR inhibitors in one half of patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
R. Sanfilippo: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Research grant / Funding (institution): Advanchen Laboratories; Research grant / Funding (institution): Amgen Dompe; Research grant / Funding (institution): AROG Pharmaceuticals; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Epizyme Inc; Research grant / Funding (institution): Galxo; Research grant / Funding (institution): Karyopharm; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer. C. Fabbroni: Research grant / Funding (institution): Advanchen Laboratories; Research grant / Funding (institution): Amgen Dompe’; Research grant / Funding (institution): AROG Pharmaceuticals; Research grant / Funding (institution): bayer; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Epizyme Inc; Research grant / Funding (institution): Glaxo; Research grant / Funding (institution): Karyopharm Pharmaceuticals; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): PharmaMar. E. Fumagalli: Research grant / Funding (institution): Advenchen Laboratories; Research grant / Funding (institution): Amgen dompe’; Research grant / Funding (institution): AROG Pharmaceuticals; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Epizyme; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): PharmaMar; Research grant / Funding (institution): Glaxo; Research grant / Funding (institution): karyopharm Pharmaceuticals; Research grant / Funding (institution): Pfizer. R. Bertulli: Research grant / Funding (institution): Karyopharm Pharmaceuticals; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Advenchen Laboratories; Research grant / Funding (institution): Amgen dompe’; Research grant / Funding (institution): AROG Pharmaceuticals; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): Daiichi Sankyo ; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Epizyme; Research grant / Funding (institution): Glaxo; Research grant / Funding (institution): PharmaMar. S. Stacchiotti: Research grant / Funding (institution): Karyopharm Pharmaceuticals; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): PharmaMar; Research grant / Funding (institution): Glaxo; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Advenche Laboratories; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): AROG Pharmaceuticals; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Epizyme; Research grant / Funding (institution): Pfizer. P.G. Casali: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bayer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Deciphera; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eisai; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Nektar Therapeutics; Research grant / Funding (institution): Advenchen Laboratories; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Blueprint Midicines; Research grant / Funding (institution): AROG Pharmaceuticals; Research grant / Funding (institution): Amgen dompe’; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Epizyme; Research grant / Funding (institution): Glaxo; Research grant / Funding (institution): KaryopharmPharmaceuticals; Research grant / Funding (institution): PharmaMar. All other authors have declared no conflicts of interest.
Resources from the same session
5011 - LCSCAF1 maintains cancer stem-like traits by stabilizing c-Myc protein and promotes metastasis and recurrence in lung cancer
Presenter: Tao Guo
Session: Poster Display session 1
Resources:
Abstract
4955 - XAF1 Enhances Temozolomide Induced Autophagic Cell Death through AMPK signaling pathway
Presenter: Mingoo Lee
Session: Poster Display session 1
Resources:
Abstract
5616 - The effect of cortisol on methylation patterns in breast cancer cell lines
Presenter: Haya Intabli
Session: Poster Display session 1
Resources:
Abstract
4649 - Global and sex-specific epigenome-wide association studies for the identification of the main methylated loci related to smoking in a Mediterranean population
Presenter: Judith Begona Ramirez Sabio
Session: Poster Display session 1
Resources:
Abstract
4984 - Whole transcriptomics analyses of mimicking Circulating Tumor Cells (CTCs) by single-cell RNA sequencing (scRNAseq)
Presenter: Jessica Garcia
Session: Poster Display session 1
Resources:
Abstract
5926 - Comparison of enzymatic- and bisulfite conversion to map the plasma cell-free methylome in cancer
Presenter: Nicole Lambert
Session: Poster Display session 1
Resources:
Abstract
5454 - Detection of low mutations in hepatocellular carcinoma by using circulating tumor DNA
Presenter: Esl Kim
Session: Poster Display session 1
Resources:
Abstract
4428 - Variants in the JAK1 and JAK2 genes in the risk and prognosis of patients with cutaneous melanoma
Presenter: Bruna Carvalho
Session: Poster Display session 1
Resources:
Abstract
4409 - P-Rex1 expression in breast cancer patients.
Presenter: Angela Lara Montero
Session: Poster Display session 1
Resources:
Abstract
4185 - Modulation of Risk of Cutaneous Melanoma Patients by Variants in STAT3 Gene and Functional Analysis
Presenter: Gabriela Gomez
Session: Poster Display session 1
Resources:
Abstract