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

Gynecologic Oncology

Volumn 136, Issue 2, 2015, Pages 246-253

  Matulonis, Ursula ^a   Vergote, Ignace ^b   Backes, Floor ^c   Martin, Lainie P ^d   McMeekin, Scott ^e   Birrer, Michael ^f   Campana, Frank ^g   Xu, Yi ^g   Egile, Coumaran ^h   Ghamande, Sharad ⁱ  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b Katholieke Universiteit   (Belgium)

^c OHIO STATE UNIVERSITY   (United States)

^d FOX CHASE CANCER CENTER   (United States)

^e UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER   (United States)

^f MASSACHUSETTS GENERAL HOSPITAL CANCER CENTER   (United States)

^g SANOFI   (United States)

^h SANOFI   (France)

ⁱ MEDICAL COLLEGE OF GEORGIA   (United States)

Author keywords

Endometrial cancer; PI3K inhibitors

Indexed keywords

ALANINE AMINOTRANSFERASE; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; DNA; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PHOSPHOINOSITIDE 3 KINASE REGULATORY SUBUNIT 1; PILARALISIB; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; PROTEIN KINASE INHIBITOR; QUINOXALINE DERIVATIVE; SULFONAMIDE;

ABDOMINAL PAIN; ADULT; ADVANCED CANCER; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALKALINE PHOSPHATASE BLOOD LEVEL; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; CANCER CHEMOTHERAPY; CANCER RESISTANCE; CANCER SURVIVAL; CHEMOTHERAPY INDUCED ANEMIA; CHEMOTHERAPY INDUCED EMESIS; DECREASED APPETITE; DIARRHEA; DNA FINGERPRINTING; DRUG EFFICACY; DRUG ERUPTION; DRUG RESPONSE; DRUG SAFETY; DRY SKIN; ENDOMETRIUM CARCINOMA; FATIGUE; FEMALE; GENE MUTATION; HISTOPATHOLOGY; HUMAN; HUMAN TISSUE; HYPERGLYCEMIA; MAJOR CLINICAL STUDY; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; OPEN STUDY; OUTCOME ASSESSMENT; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEIN EXPRESSION; PRURITUS; RECURRENT DISEASE; SIDE EFFECT; SURVIVAL RATE; SURVIVAL TIME; WEIGHT REDUCTION; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL; ENDOMETRIAL NEOPLASMS; ENZYMOLOGY; MIDDLE AGED; NEOPLASM RECURRENCE, LOCAL; VERY ELDERLY;

AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS; ENDOMETRIAL NEOPLASMS; FEMALE; HUMANS; MIDDLE AGED; NEOPLASM RECURRENCE, LOCAL; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN KINASE INHIBITORS; QUINOXALINES; SULFONAMIDES;

EID: 84923108243     PISSN: 00908258     EISSN: 10956859     Source Type: Journal    
DOI: 10.1016/j.ygyno.2014.12.019     Document Type: Article

References (40)

1. R. Siegel, J. Ma, Z. Zou, and A. Jemal Cancer statistics CA Cancer J Clin 64 1 2014 9 29
2. National Cancer Institute SEER cancer statistics factsheets: endometrial cancer [Available at] http://seer.cancer.gov/statfacts/html/corp.html 2014 [Accessed July 2014]
3. S.M. Ueda, D.S. Kapp, M.K. Cheung, J.Y. Shin, K. Osann, A. Husain, et al. Trends in demographic and clinical characteristics in women diagnosed with corpus cancer and their potential impact on the increasing number of deaths Am J Obstet Gynecol 198 2 2008 218 226
4. L.S. Bradford, J.A. Rauh-Hain, J. Schorge, M.J. Birrer, and D.S. Dizon Advances in the management of recurrent endometrial cancer Am J Clin Oncol 2013 [Epub ahead of print]
5. N. Bansal, V. Yendluri, and R.M. Wenham The molecular biology of endometrial cancers and the implications for pathogenesis, classification, and targeted therapies Cancer Control 16 1 2009 8 13
6. B.M. Slomovitz, and R.L. Coleman The PI3K/AKT/mTOR pathway as a therapeutic target in endometrial cancer Clin Cancer Res 18 21 2012 5856 5864
7. J.L. Hecht, and G.L. Mutter Molecular and pathologic aspects of endometrial carcinogenesis J Clin Oncol 24 29 2006 4783 4791
8. J.V. Bokhman Two pathogenetic types of endometrial carcinoma Gynecol Oncol 15 1 1983 10 17
9. The Cancer Genome Atlas Research Network Integrated genomic characterization of endometrial carcinoma Nature 497 7447 2013 67 73
10. G.L. Mutter, M.C. Lin, J.T. Fitzgerald, J.B. Kum, J.P. Baak, J.A. Lees, et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers J Natl Cancer Inst 92 11 2000 924 930
11. H.B. Salvesen, S.L. Carter, M. Mannelqvist, A. Dutt, G. Getz, I.M. Stefansson, et al. Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation Proc Natl Acad Sci U S A 106 12 2009 4834 4839
12. K.D. Courtney, R.B. Corcoran, and J.A. Engelman The PI3K pathway as drug target in human cancer J Clin Oncol 28 6 2010 1075 1083
13. K. Oda, D. Stokoe, Y. Taketani, and F. McCormick High frequency of coexistent mutations of PIK3CA and PTEN genes in endometrial carcinoma Cancer Res 65 23 2005 10669 10673
14. A. Velasco, E. Bussaglia, J. Pallares, X. Dolcet, D. Llobet, M. Encinas, et al. PIK3CA gene mutations in endometrial carcinoma: correlation with PTEN and K-RAS alterations Hum Pathol 37 11 2006 1465 1472
15. S. Kang, S.S. Seo, H.J. Chang, C.W. Yoo, S.Y. Park, and S.M. Dong Mutual exclusiveness between PIK3CA and KRAS mutations in endometrial carcinoma Int J Gynecol Cancer 18 6 2008 1339 1343
16. I. Ray-Coquard, L. Favier, B. Weber, C. Roemer-Becuwe, P. Bougnoux, M. Fabbro, et al. Everolimus as second- or third-line treatment of advanced endometrial cancer: ENDORAD, a phase II trial of GINECO Br J Cancer 108 9 2013 1771 1777
17. N. Colombo, D.S. McMeekin, P.E. Schwartz, C. Sessa, P.A. Gehrig, R. Holloway, et al. Ridaforolimus as a single agent in advanced endometrial cancer: results of a single-arm, phase 2 trial Br J Cancer 108 5 2013 1021 1026
18. A.M. Oza, L. Elit, M.S. Tsao, S. Kamel-Reid, J. Biagi, D.M. Provencher, et al. Phase II study of temsirolimus in women with recurrent or metastatic endometrial cancer: a trial of the NCIC Clinical Trials Group J Clin Oncol 29 24 2011 3278 3285
19. B.M. Slomovitz, K.H. Lu, T. Johnston, R.L. Coleman, M. Munsell, R.R. Broaddus, et al. A phase 2 study of the oral mammalian target of rapamycin inhibitor, everolimus, in patients with recurrent endometrial carcinoma Cancer 116 23 2010 5415 5419
20. A.P. Myers New strategies in endometrial cancer: targeting the PI3K/mTOR pathway - the devil is in the details Clin Cancer Res 19 19 2013 5264 5274
21. V. Makker, F.O. Recio, L. Ma, U. Matulonis, J. O'Hara Lauchle, H. Parmar, et al. Phase II trial of GDC-0980 (dual PI3K/mTOR inhibitor) in patients with advanced endometrial carcinoma: final study results J Clin Oncol 32 2014 5513 [Abstr]
22. P. Konstantinopoulos, V. Makker, W.T. Barry, J. Liu, N.S. Horowitz, M.J. Birrer, et al. Phase II, single stage, cohort expansion study of MK-2206 in recurrent endometrial serous cancer J Clin Oncol 32 2014 5515 [Abstr]
23. S.S. Sidhu, C. Egile, M. Malfilatre, C. Lefranc, Y. Ruffin, J. Ma, et al. Antitumor activity of Pimasertib in combination with SAR245409 or SAR245408 in human primary colorectal cancer xenograft models bearing PI3K/KRAS and KRAS Mutations Proceedings of the 104th annual meeting of the American Association for Cancer Research; 2013
24. G.I. Shapiro, J. Rodon, C. Bedell, E.L. Kwak, J. Baselga, I. Brana, et al. Phase I safety, pharmacokinetic, and pharmacodynamic study of SAR245408 (XL147), an oral pan-class I PI3K inhibitor, in patients with advanced solid tumors Clin Cancer Res 20 1 2014 233 245
25. T.F. Cloughesy, P.S. Mischel, A.M.P. Omuro, M. Prados, P.Y. Wen, B. Wu, et al. Tumor pharmacokinetics (PK) and pharmacodynamics (PD) of SAR245409 (XL765) and SAR245408 (XL147) administered as single agents to patients with recurrent glioblastoma (GBM): an Ivy Foundation early-phase clinical trials consortium study J Clin Oncol 31 2013 [Suppl.]
26. J.R. Brown, M.S. Davids, J. Rodon, P. Abrisqueta, C. Egile, R. Ruiz-Soto, et al. Update on the safety and efficacy of the pan class I PI3K inhibitor SAR245408 (XL147) in chronic lymphocytic leukemia and non-Hodgkin's lymphoma patients Blood 122 21 2013 4170
27. R. Bourgon, S. Lu, Y. Yan, M.R. Lackner, W. Wang, V. Weigman, et al. High-throughput detection of clinically relevant mutations in archived tumor samples by multiplexed PCR and next-generation sequencing Clin Cancer Res 20 8 2014 2080 2091
28. A. Leary, S. Rajpar, S. Mace, P. Duvillard, A. Rey, S. Gouy, et al. Advanced or recurrent endometrial cancer (EC) and co-occurring mutations in multiple oncogenic pathways J Clin Oncol 32 2014 5514 [Abstr]
29. B. Markman, J. Tabernero, I. Krop, G.I. Shapiro, L. Siu, L.C. Chen, et al. Phase I safety, pharmacokinetic, and pharmacodynamic study of the oral phosphatidylinositol-3-kinase and mTOR inhibitor BGT226 in patients with advanced solid tumors Ann Oncol 23 9 2012 2399 2408
30. C. Bendell, J. Rodon, H.A. Burris, M. de Jonge, J. Verweij, D. Birle, et al. Phase I, dose-escalation study of BKM120, an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors J Clin Oncol 30 3 2012 282 290
31. H.-T. Arkenau, S. Fields Jones, C. Kurkjian, J.R. Infante, S. Pant, H.A. Burris, et al. The PI3K/mTOR inhibitor BEZ235 given twice daily for the treatment of patients (pts) with advanced solid tumors J Clinoncol 30 2012 3097 [Abstr]
32. A.J. Wagner, J.C. Bendell, S. Dolly, J.A. Morgan, J.A. Ware, J. Fredrickson, et al. A first-in-human phase I study to evaluate GDC-0980, an oral PI3K/mTOR inhibitor, administered QD in patients with advanced solid tumors J Concol 29 2011 3020 [Abstr]
33. D.S. Hong, D.W. Bowles, G.S. Falchook, W.A. Messersmith, G.C. George, C.L. O'Bryant, et al. A multicenter phase I trial of PX-866, an oral irreversible phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors Clin Cancer Res 18 15 2012 4173 4182
34. N. Mu, Y. Zhu, Y. Wang, H. Zhang, and F. Xue Insulin resistance: a significant risk factor of endometrial cancer Gynecol Oncol 125 3 2012 751 757
35. A.P. Myers, R. Broaddus, V. Makker, P.A. Konstantinopoulos, R. Drapkin, N.S. Horowitz, et al. Phase II, two-stage, two-arm, PIK3CA mutation stratified trial of MK-2206 in recurrent endometrial cancer (EC) J Clin Oncol 31 2013 5524 [Suppl.; abstr]
36. H.J. Mackay, E.A. Eisenhauer, S. Kamel-Reid, M. Tsao, B. Clarke, K. Karakasis, et al. Molecular determinants of outcome with mammalian target of rapamycin inhibition in endometrial cancer Cancer 120 4 2014 603 610
37. J. Rodon, R. Dienstmann, V. Serra, and J. Tabernero Development of PI3K inhibitors: lessons learned from early clinical trials Nat Rev Clin Oncol 10 3 2013 143 153
38. C. Kollmannsberger, H. Hirte, L.L. Siu, J. Mazurka, K. Chi, L. Elit, et al. Temsirolimus in combination with carboplatin and paclitaxel in patients with advanced solid tumors: a NCIC-CTG, phase I, open-label dose-escalation study (IND 179) Ann Oncol 23 1 2012 238 244
39. E.A. Alvarez, W.E. Brady, J.L. Walker, J. Rotmensch, X.C. Zhou, J.E. Kendrick, et al. Phase II trial of combination bevacizumab and temsirolimus in the treatment of recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study Gynecol Oncol 129 1 2013 22 27
40. J. Baselga, M. Campone, M. Piccart, H.A. Burris III, H.S. Rugo, T. Sahmoud, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer N Engl J Med 366 6 2012 520 529