Phase II study of the PI3K inhibitor pilaralisib (SAR245408; XL147) in patients with advanced or recurrent endometrial carcinoma

Ursula Matulonis, Ignace Vergote, Floor Backes, Lainie P. Martin, Scott McMeekin, Michael Birrer, Frank Campana, Yi Xu, Coumaran Egile, Sharad A Ghamande

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Objective. 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. Methods. 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 600 mg capsules or 400 mg tablets once daily. Primary endpoints were objective response rate (ORR), proportion of patients with progression-free survival (PFS) > 6 months 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. Results. 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 > 6 months 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%). Conclusions. Pilaralisib was associated with a favorable safety profile and minimal antitumor activity in advanced or recurrent endometrial carcinoma.

Original languageEnglish (US)
Pages (from-to)246-253
Number of pages8
JournalGynecologic Oncology
Volume136
Issue number2
DOIs
StatePublished - Feb 1 2015

Fingerprint

1-Phosphatidylinositol 4-Kinase
Endometrial Neoplasms
Neoplasms
Exanthema
Safety
Disease-Free Survival
Diarrhea
PTEN Phosphohydrolase
Drug Therapy
Protein Deficiency
Investigational Therapies
XL147
Alanine Transaminase
Tablets
Capsules
Fatigue
Mutation
DNA
Therapeutics

Keywords

  • Endometrial cancer
  • PI3K inhibitors

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Phase II study of the PI3K inhibitor pilaralisib (SAR245408; XL147) in patients with advanced or recurrent endometrial carcinoma. / Matulonis, Ursula; Vergote, Ignace; Backes, Floor; Martin, Lainie P.; McMeekin, Scott; Birrer, Michael; Campana, Frank; Xu, Yi; Egile, Coumaran; Ghamande, Sharad A.

In: Gynecologic Oncology, Vol. 136, No. 2, 01.02.2015, p. 246-253.

Research output: Contribution to journalArticle

Matulonis, U, Vergote, I, Backes, F, Martin, LP, McMeekin, S, Birrer, M, Campana, F, Xu, Y, Egile, C & Ghamande, SA 2015, 'Phase II study of the PI3K inhibitor pilaralisib (SAR245408; XL147) in patients with advanced or recurrent endometrial carcinoma', Gynecologic Oncology, vol. 136, no. 2, pp. 246-253. https://doi.org/10.1016/j.ygyno.2014.12.019
Matulonis, Ursula ; Vergote, Ignace ; Backes, Floor ; Martin, Lainie P. ; McMeekin, Scott ; Birrer, Michael ; Campana, Frank ; Xu, Yi ; Egile, Coumaran ; Ghamande, Sharad A. / Phase II study of the PI3K inhibitor pilaralisib (SAR245408; XL147) in patients with advanced or recurrent endometrial carcinoma. In: Gynecologic Oncology. 2015 ; Vol. 136, No. 2. pp. 246-253.
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abstract = "Objective. 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. Methods. 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 600 mg capsules or 400 mg tablets once daily. Primary endpoints were objective response rate (ORR), proportion of patients with progression-free survival (PFS) > 6 months 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. Results. 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 > 6 months 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{\%}). Conclusions. Pilaralisib was associated with a favorable safety profile and minimal antitumor activity in advanced or recurrent endometrial carcinoma.",
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T1 - Phase II study of the PI3K inhibitor pilaralisib (SAR245408; XL147) in patients with advanced or recurrent endometrial carcinoma

AU - Matulonis, Ursula

AU - Vergote, Ignace

AU - Backes, Floor

AU - Martin, Lainie P.

AU - McMeekin, Scott

AU - Birrer, Michael

AU - Campana, Frank

AU - Xu, Yi

AU - Egile, Coumaran

AU - Ghamande, Sharad A

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N2 - Objective. 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. Methods. 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 600 mg capsules or 400 mg tablets once daily. Primary endpoints were objective response rate (ORR), proportion of patients with progression-free survival (PFS) > 6 months 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. Results. 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 > 6 months 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%). Conclusions. Pilaralisib was associated with a favorable safety profile and minimal antitumor activity in advanced or recurrent endometrial carcinoma.

AB - Objective. 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. Methods. 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 600 mg capsules or 400 mg tablets once daily. Primary endpoints were objective response rate (ORR), proportion of patients with progression-free survival (PFS) > 6 months 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. Results. 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 > 6 months 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%). Conclusions. Pilaralisib was associated with a favorable safety profile and minimal antitumor activity in advanced or recurrent endometrial carcinoma.

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