Open AccessPhase II Study of BEZ235 versus Everolimus in Patients with Mammalian Target of Rapamycin Inhibitor‐Naïve Advanced Pancreatic Neuroendocrine Tumors
Author(s) -
Salazar Ramon,
GarciaCarbonero Rocio,
Libutti Steven K.,
Hendifar Andrew E.,
Custodio Ana,
Guimbaud Rosine,
LombardBohas Catherine,
Ricci Sergio,
Klümpen HeinzJosef,
Capdevila Jaume,
Reed Nicholas,
Walenkamp Annemiek,
Grande Enrique,
Safina Sufiya,
Meyer Tim,
Kong Oliver,
Salomon Herve,
Tavorath Ranjana,
Yao James C.
Publication year - 2018
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2017-0144
Subject(s) - everolimus , medicine , neuroendocrine tumors , clinical endpoint , pi3k/akt/mtor pathway , tolerability , adverse effect , hazard ratio , oncology , temsirolimus , fulvestrant , gastroenterology , randomized controlled trial , confidence interval , cancer , discovery and development of mtor inhibitors , breast cancer , estrogen receptor , signal transduction , biochemistry , chemistry
Lessons Learned Treatment with BEZ235 has not been shown to demonstrate increased efficacy compared with everolimus and may be associated with a poorer tolerability profile. The hypothesis of dual targeting of the phosphatidylinositol 3‐kinase and mammalian target of rapamycin pathways in patients with advanced pancreatic neuroendocrine tumors may warrant further study using other agents.Background This phase II study investigated whether targeting the phosphatidylinositol 3‐kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway via PI3K, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) inhibition using BEZ235 may be more effective than mTORC1 inhibition with everolimus in patients with advanced pancreatic neuroendocrine tumors (pNET) who are naïve to mTOR inhibitor therapy. Methods Patients with advanced pNET were randomized (1:1) to oral BEZ235 400 mg twice daily or oral everolimus 10 mg once daily on a continuous dosing schedule. The primary endpoint was progression‐free survival (PFS). Secondary endpoints included safety, overall response rate (ORR), overall survival (OS), and time to treatment failure. Results Enrollment in this study was terminated early (62 enrolled of the 140 planned). The median PFS was 8.2 months (95% confidence interval [CI]: 5.3 to not evaluable [NE]) with BEZ235 versus 10.8 months (95% CI: 8.1–NE) with everolimus (hazard ratio 1.53; 95% CI: 0.72–3.25). The most commonly reported all‐grade adverse events (>50% of patients regardless of study treatment relationship) with BEZ235 were diarrhea (90.3%), stomatitis (74.2%), and nausea (54.8%). Conclusion BEZ235 treatment in mTOR inhibitor‐naïve patients with advanced pNET did not demonstrate increased efficacy compared with everolimus and may be associated with a poorer tolerability profile.