dc.contributor.author | Del Campo, JM | |
dc.contributor.author | Birrer, M | |
dc.contributor.author | Davis, C | |
dc.contributor.author | Fujiwara, K | |
dc.contributor.author | Gollerkeri, A | |
dc.contributor.author | Gore, M | |
dc.contributor.author | Houk, B | |
dc.contributor.author | Lau, S | |
dc.contributor.author | Poveda, A | |
dc.contributor.author | González-Martín, A | |
dc.contributor.author | Muller, C | |
dc.contributor.author | Muro, K | |
dc.contributor.author | Pierce, K | |
dc.contributor.author | Suzuki, M | |
dc.contributor.author | Vermette, J | |
dc.contributor.author | Oza, A | |
dc.date.accessioned | 2017-05-03T14:32:33Z | |
dc.date.issued | 2016-07 | |
dc.identifier.citation | Gynecologic oncology, 2016, 142 (1), pp. 62 - 69 | |
dc.identifier.issn | 0090-8258 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/633 | |
dc.identifier.eissn | 1095-6859 | |
dc.identifier.doi | 10.1016/j.ygyno.2016.04.019 | |
dc.description.abstract | Objective 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.format | Print-Electronic | |
dc.format.extent | 62 - 69 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.rights.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
dc.subject | Humans | |
dc.subject | Endometrial Neoplasms | |
dc.subject | Neoplasm Recurrence, Local | |
dc.subject | Morpholines | |
dc.subject | Pyridones | |
dc.subject | Pyrimidines | |
dc.subject | Triazines | |
dc.subject | Protein Kinase Inhibitors | |
dc.subject | Aged | |
dc.subject | Aged, 80 and over | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Phosphatidylinositol 3-Kinases | |
dc.subject | TOR Serine-Threonine Kinases | |
dc.subject | Biomarkers, Tumor | |
dc.subject | Phosphoinositide-3 Kinase Inhibitors | |
dc.title | A randomized phase II non-comparative study of PF-04691502 and gedatolisib (PF-05212384) in patients with recurrent endometrial cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-04-16 | |
rioxxterms.versionofrecord | 10.1016/j.ygyno.2016.04.019 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2016-07 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Gynecologic oncology | |
pubs.issue | 1 | |
pubs.notes | No 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-status | Published | |
pubs.volume | 142 | |
pubs.embargo.terms | No embargo | |
dc.contributor.icrauthor | Gore, Martin | |