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|Ref Type||Journal Article|
|Authors||Matulonis U, Vergote I, Backes F, Martin LP, McMeekin S, Birrer M, Campana F, Xu Y, Egile C, Ghamande S|
|Title||Phase II study of the PI3K inhibitor pilaralisib (SAR245408; XL147) in patients with advanced or recurrent endometrial carcinoma.|
|Abstract Text||Patients with endometrial carcinoma who progress after first-line chemotherapy have a poor prognosis. Phosphoinositide 3-kinase (PI3K) inhibitors are investigational treatment options in this setting. This study evaluated the efficacy and safety of the PI3K inhibitor pilaralisib (SAR245408; XL147) in advanced or recurrent endometrial carcinoma.This Phase II, multicenter, single-arm, open-label study enrolled patients with histologically confirmed advanced or recurrent endometrial carcinoma, who had received one or two prior chemotherapy regimens. Patients received pilaralisib 600mg capsules or 400mg tablets once daily. Primary endpoints were objective response rate (ORR), proportion of patients with progression-free survival (PFS) >6months and safety. Molecular profiling in archival tumor tissue and circulating tumor DNA were performed to identify molecular markers associated with response or resistance to pilaralisib.67 patients were enrolled, of which 50 and 17 patients had received one or two prior regimens, respectively. Complete or partial tumor responses occurred in two patients each (ORR 6.0%); three had tumors with normal PTEN expression and PIK3R1 mutations and one had a tumor with PTEN protein deficiency. However, there was no association between molecular alterations and clinical activity. Rate of PFS>6months was 11.9%. The most commonly reported treatment-related adverse events (AEs) were rash (40.3%), diarrhea (37.3%) and fatigue (28.4%). The most commonly reported treatment-related grade ≥3 AEs were rash (9.0%), diarrhea (4.5%) and increased alanine aminotransferase (4.5%).Pilaralisib was associated with a favorable safety profile and minimal antitumor activity in advanced or recurrent endometrial carcinoma.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|PIK3CA||L456R||missense||unknown||PIK3CA L456R lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). L456R has been identified in sequencing studies (PMID: 25528496, PMID: 30503610), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Feb 2020).|
|PIK3CA||M1043T||missense||unknown||PIK3CA M1043T lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). M1043T has been identified in sequencing studies (PMID: 28830922, PMID: 25528496, PMID: 23370426), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Feb 2020).|
|PIK3CA||Q75E||missense||unknown||PIK3CA Q75E lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). Q75E has been identified in the scientific literature (PMID: 25528496, PMID: 30333046, PMID: 28781987), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Feb 2020).|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||endometrial carcinoma||not applicable||XL147||Phase II||Actionable||In a Phase II trial, Pilaralisib (XL147) treatment resulted in an objective response rate of 6% (4/67) in patients with endometrial carcinoma, although anti-tumor activity is not associated with molecular alterations in PTEN and PIK3R1 (PMID: 25528496).||25528496|