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
3909 - Spectrum of pathogenic germline mutations in Chinese lung cancer patients through next-generation sequencing
Presenter: Ying Huang
Session: Poster Display session 1
Resources:
Abstract
3061 - Poor prognostic impact of NTRK2 gene variation in Esophageal Squamous Cell Carcinoma
Presenter: Ye Chen
Session: Poster Display session 1
Resources:
Abstract
4735 - Mutation profile of Tibetan lung cancer revealed by Whole Exome Sequencing
Presenter: Xin Wang
Session: Poster Display session 1
Resources:
Abstract
5236 - Synergistic activity between niraparib and chemotherapy in colorectal cancer: molecular determinants from a preclinical model
Presenter: Pietro Paolo Vitiello
Session: Poster Display session 1
Resources:
Abstract
4051 - cRGDfK (cRGD) conjugated Pyropheophor¬bide-a (Pyro), a new tumor photodynamic agent, is highly accumulated and specific in tumor cell killing
Presenter: Fengwei Wang
Session: Poster Display session 1
Resources:
Abstract
859 - The expression of MMR, CD133 and the presence of p53 wt predict the response to Cabazitaxel in malignant neural tumors cell lines.
Presenter: Kevin Doello
Session: Poster Display session 1
Resources:
Abstract
2497 - IKS01, a next generation antibody drug conjugate (ADC) designed to be efficacious in tumors with low and moderate levels of folate receptor expression
Presenter: Jenny Thirlway
Session: Poster Display session 1
Resources:
Abstract
1636 - Novel Non-Camptothecin Compounds with Antiproliferative Activities against Breast Cancer Cells
Presenter: Wen-shan Li
Session: Poster Display session 1
Resources:
Abstract
3443 - Sensitization of estrogen receptor-positive breast cancer cells to tamoxifen by novel epi-oligomycin A
Presenter: Margarita Yastrebova
Session: Poster Display session 1
Resources:
Abstract
840 - Autophagy inhibition enhances leflunomide-induced cytotoxicity in human bladder cancer cells
Presenter: Li Cheng
Session: Poster Display session 1
Resources:
Abstract