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dc.contributor.authorDel Campo, JM
dc.contributor.authorBirrer, M
dc.contributor.authorDavis, C
dc.contributor.authorFujiwara, K
dc.contributor.authorGollerkeri, A
dc.contributor.authorGore, M
dc.contributor.authorHouk, B
dc.contributor.authorLau, S
dc.contributor.authorPoveda, A
dc.contributor.authorGonzález-Martín, A
dc.contributor.authorMuller, C
dc.contributor.authorMuro, K
dc.contributor.authorPierce, K
dc.contributor.authorSuzuki, M
dc.contributor.authorVermette, J
dc.contributor.authorOza, A
dc.date.accessioned2017-05-03T14:32:33Z
dc.date.issued2016-07
dc.identifier.citationGynecologic oncology, 2016, 142 (1), pp. 62 - 69
dc.identifier.issn0090-8258
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/633
dc.identifier.eissn1095-6859
dc.identifier.doi10.1016/j.ygyno.2016.04.019
dc.description.abstractObjective PF-04691502 and gedatolisib (PF-05212384) are potent, dual PI3K/mTOR inhibitors. This phase II study (B1271004) was conducted in patients with recurrent endometrial cancer following platinum-containing chemotherapy. The primary endpoint was to assess clinical benefit response (complete or partial response, or stable disease for ≥16weeks) following treatment with PF-04691502 or gedatolisib.Methods The main study consisted of four independent arms based on a Simon two-stage design. Patients were assigned to putative PI3K-basal (PF-04691502 or gedatolisib) or PI3K-activated (PF-04691502 or gedatolisib) arms based on stathmin-low or stathmin-high tumor expression, respectively. Japanese patients were also enrolled in a separate lead-in cohort.Results In stage 1 (main study), eighteen patients were randomized to PF-04691502 and 40 to gedatolisib. The two PF-04691502 arms were discontinued early due to unacceptable toxicity, including pneumonia and pneumonitis. The most common treatment-related adverse events associated with gedatolisib were nausea (53%), mucosal inflammation (50%), decreased appetite (40%), diarrhea (38%), fatigue (35%), and dysgeusia and vomiting (each 30%). Clinical benefit response rate was 53% (10/19) in the gedatolisib/stathmin-low arm and 26% (5/19) in the gedatolisib/stathmin-high arm. Safety profile and pharmacokinetic characteristics of both drugs in the Japanese lead-in cohort were comparable to the Western population.Conclusions Gedatolisib administered by weekly intravenous infusion demonstrated acceptable tolerability and moderate activity in patients with recurrent endometrial cancer. PF-04691502 daily oral dosing was not well tolerated. Clinical benefit response criteria for proceeding to stage 2 were only met in the gedatolisib/stathmin-low arm. Stathmin-high expression did not correlate with greater treatment efficacy. ClinicalTrials.gov registration ID: NCT01420081.
dc.formatPrint-Electronic
dc.format.extent62 - 69
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.subjectHumans
dc.subjectEndometrial Neoplasms
dc.subjectNeoplasm Recurrence, Local
dc.subjectMorpholines
dc.subjectPyridones
dc.subjectPyrimidines
dc.subjectTriazines
dc.subjectProtein Kinase Inhibitors
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectPhosphatidylinositol 3-Kinases
dc.subjectTOR Serine-Threonine Kinases
dc.subjectBiomarkers, Tumor
dc.subjectPhosphoinositide-3 Kinase Inhibitors
dc.titleA randomized phase II non-comparative study of PF-04691502 and gedatolisib (PF-05212384) in patients with recurrent endometrial cancer.
dc.typeJournal Article
dcterms.dateAccepted2016-04-16
rioxxterms.versionofrecord10.1016/j.ygyno.2016.04.019
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2016-07
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfGynecologic oncology
pubs.issue1
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume142
pubs.embargo.termsNo embargo
dc.contributor.icrauthorGore, Martin


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