Phase I/II study of pilaralisib (SAR245408) in combination with trastuzumab or trastuzumab plus paclitaxel in trastuzumab-refractory HER2-positive metastatic breast cancer

Breast Cancer Research and Treatment

Volumn 149, Issue 1, 2015, Pages 151-161

  Tolaney, Sara ^a   Burris, Howard ^b   Gartner, Elaina ^c   Mayer, Ingrid A ^d   Saura, Cristina ^e   Maurer, Matthew ^f   Ciruelos, Eva ^g   Garcia, Agustin A ^h   Campana, Frank ⁱ   Wu, Bin ⁱ   Xu, Yi ⁱ   Jiang, Jason ^j   Winer, Eric ^a   Krop, Ian ^a  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b SARAH CANNON RESEARCH INSTITUTE   (United States)

^c WAYNE STATE UNIVERSITY   (United States)

^d VANDERBILT INGRAM CANCER CENTER   (United States)

^e HOSPITAL UNIVERSITARI VALL D HEBRON   (Spain)

^f NewYork Presbyterian Hospital   (United States)

^g HOSPITAL UNIVERSITARIO 12 DE OCTUBRE   (Spain)

^h UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

ⁱ SANOFI   (United States)

^j SANOFI   (France)

more..

Author keywords

HER2 positive; Metastatic breast cancer; PI3K; Pilaralisib; Trastuzumab

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR 2; PACLITAXEL; PILARALISIB; TRASTUZUMAB; ANTINEOPLASTIC AGENT; MONOCLONAL ANTIBODY; PHOSPHATIDYLINOSITOL 3 KINASE; QUINOXALINE DERIVATIVE; SULFONAMIDE;

ADULT; AGED; ALOPECIA; ANEMIA; AREA UNDER THE CURVE; ARTICLE; BREAST METASTASIS; CANCER COMBINATION CHEMOTHERAPY; CLINICAL ARTICLE; CLINICAL EFFECTIVENESS; CLINICAL EVALUATION; CONTROLLED STUDY; DECREASED APPETITE; DIARRHEA; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG EXPOSURE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DRY SKIN; ERYTHEMA; FATIGUE; FEMALE; GENE; GENE MUTATION; HUMAN; HYPERGLYCEMIA; HYPOKALEMIA; LEUKOCYTE COUNT; LEUKOPENIA; LOADING DRUG DOSE; MAXIMUM TOLERATED DOSE; MONOTHERAPY; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; PERIPHERAL EDEMA; PERIPHERAL NEUROPATHY; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PIK3CA GENE; PRIORITY JOURNAL; RASH; TIME TO MAXIMUM PLASMA CONCENTRATION; TREATMENT OUTCOME; ANTAGONISTS AND INHIBITORS; BREAST NEOPLASMS; CLINICAL TRIAL; GENETICS; MIDDLE AGED; PATHOLOGY;

ADULT; AGED; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BREAST NEOPLASMS; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HUMANS; MAXIMUM TOLERATED DOSE; MIDDLE AGED; PACLITAXEL; PHOSPHATIDYLINOSITOL 3-KINASES; QUINOXALINES; RECEPTOR, ERBB-2; SULFONAMIDES;

EID: 84925503345     PISSN: 01676806     EISSN: 15737217     Source Type: Journal    
DOI: 10.1007/s10549-014-3248-4     Document Type: Article

References (30)

1. Paik S, Hazan R, Fisher ER, Sass RE, Fisher B, Redmond C, Schlessinger J, Lippman ME, King CR (1990) Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein overexpression in primary breast cancer. J Clin Oncol 8:103–112
2. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353:1673–1684
3. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792
4. Nahta R, Esteva FJ (2006) HER2 therapy: molecular mechanisms of trastuzumab resistance. Breast Cancer Res 8:215
5. Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D (2006) Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 355:2733–2743
6. Swain SM, Kim SB, Cortes J, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Knott A, Clark E, Ross G, Benyunes MC, Baselga J (2013) Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 14:461–471
7. Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM (2012) Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 366:109–119
8. Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Dieras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K (2012) Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 367:1783–1791
9. Singh JC, Jhaveri K, Esteva FJ (2014) HER2-positive advanced breast cancer: optimizing patient outcomes and opportunities for drug development. Br J Cancer 111:1888–1898
10. Courtney KD, Corcoran RB, Engelman JA (2010) The PI3K pathway as drug target in human cancer. J Clin Oncol 28:1075–1083
11. Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, Neve RM, Kuo WL, Davies M, Carey M, Hu Z, Guan Y, Sahin A, Symmans WF, Pusztai L, Nolden LK, Horlings H, Berns K, Hung MC, van de Vijver MJ, Valero V, Gray JW, Bernards R, Mills GB, Hennessy BT (2008) An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res 68:6084–6091
12. Cancer Genome Atlas Network (2012) Comprehensive molecular portraits of human breast tumours. Nature 490:61–70
13. Saal LH, Holm K, Maurer M, Memeo L, Su T, Wang X, Yu JS, Malmstrom PO, Mansukhani M, Enoksson J, Hibshoosh H, Borg A, Parsons R (2005) PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res 65:2554–2559
14. Berns K, Horlings HM, Hennessy BT, Madiredjo M, Hijmans EM, Beelen K, Linn SC, Gonzalez-Angulo AM, Stemke-Hale K, Hauptmann M, Beijersbergen RL, Mills GB, van de Vijver MJ, Bernards R (2007) A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell 12:395–402
15. Isakoff SJ, Engelman JA, Irie HY, Luo J, Brachmann SM, Pearline RV, Cantley LC, Brugge JS (2005) Breast cancer-associated PIK3CA mutations are oncogenic in mammary epithelial cells. Cancer Res 65:10992–11000
16. Hu L, Hofmann J, Lu Y, Mills GB, Jaffe RB (2002) Inhibition of phosphatidylinositol 3′-kinase increases efficacy of paclitaxel in in vitro and in vivo ovarian cancer models. Cancer Res 62:1087–1092
17. Mondesire WH, Jian W, Zhang H, Ensor J, Hung MC, Mills GB, Meric-Bernstam F (2004) Targeting mammalian target of rapamycin synergistically enhances chemotherapy-induced cytotoxicity in breast cancer cells. Clin Cancer Res 10:7031–7042
18. Andre F, O’Regan R, Ozguroglu M, Toi M, Xu B, Jerusalem G, Masuda N, Wilks S, Arena F, Isaacs C, Yap YS, Papai Z, Lang I, Armstrong A, Lerzo G, White M, Shen K, Litton J, Chen D, Zhang Y, Ali S, Taran T, Gianni L (2014) Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol 15:580–591
19. Saura C, Bendell J, Jerusalem G, Su S, Ru Q, De Buck S, Mills D, Ruquet S, Bosch A, Urruticoechea A, Beck JT, Di Tomaso E, Sternberg DW, Massacesi C, Hirawat S, Dirix L, Baselga J (2014) Phase Ib study of buparlisib plus trastuzumab in patients with HER2-positive advanced or metastatic breast cancer that has progressed on trastuzumab-based therapy. Clin Cancer Res 20:1935–1945
20. Shapiro GI, Rodon J, Bedell C, Kwak EL, Baselga J, Brana I, Pandya SS, Scheffold C, Laird AD, Nguyen LT, Xu Y, Egile C, Edelman G (2014) 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 20:233–245
21. Brown JR, Davids MS, Rodon J, Abrisqueta P, Egile C, Ruiz-Soto R, Awan F (2013) 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 122:4170
22. Li M, Diehl F, Dressman D, Vogelstein B, Kinzler KW (2006) BEAMing up for detection and quantification of rare sequence variants. Nat Methods 3:95–97
23. Diehl F, Li M, He Y, Kinzler KW, Vogelstein B, Dressman D (2006) BEAMing: single-molecule PCR on microparticles in water-in-oil emulsions. Nat Methods 3:551–559
24. Sidhu SS, Egile C, Malfilatre M, Lefranc C, Ruffin Y, Ma J, Hsu K, Lager J, Marzabal S, Ogden JA, Vincent L (2013) Antitumor activity of pimasertib in combination with SAR245409 or SAR245408 in human primary colorectal cancer xenograft models bearing PI3K/KRAS and KRAS mutations. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research, 2013 Apr 6–10. Washington, DC
25. Bendell C, Rodon J, Burris HA, de Jonge M, Verweij J, Birle D, Demanse D, De Buck SS, Ru QC, Peters M, Goldbrunner M, Baselga J (2012) Phase I, dose-escalation study of BKM120, an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors. J Clin Oncol 30:282–290
26. Markman B, Tabernero J, Krop I, Shapiro GI, Siu L, Chen LC, Mita M, Melendez CM, Stutvoet S, Birle D, Anak O, Hackl W, Baselga J (2012) 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 23:2399–2408
27. Rodon J, Brana I, Siu LL, De Jonge MJ, Homji N, Mills D, Di Tomaso E, Sarr C, Trandafir L, Massacesi C, Eskens F, Bendell JC (2014) Phase I dose-escalation and -expansion study of buparlisib (BKM120), an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors. Invest New Drugs 32:670–681
28. Papadopoulos K, Tabernero J, Markman B, Patnaik A, Tolcher A, Baselga J, Shi W, Egile C, Ruiz-Soto R, Laird AD, Miles D, Lorusso PM (2014) Phase I safety, pharmacokinetic and pharmacodynamic study of SAR245409 (XL765), a novel, orally administered PI3K/mTOR inhibitor in patients with advanced solid tumors. Clin Cancer Res 20:2445–2456
29. Wallin JJ, Guan J, Prior WW, Lee LB, Berry L, Belmont LD, Koeppen H, Belvin M, Friedman LS, Sampath D (2012) GDC-0941, a novel class I selective PI3K inhibitor, enhances the efficacy of docetaxel in human breast cancer models by increasing cell death in vitro and in vivo. Clin Cancer Res 18:3901–3911
30. Blanco E, Sangai T, Wu S, Hsiao A, Ruiz-Esparza GU, Gonzalez-Delgado CA, Cara FE, Granados-Principal S, Evans KW, Akcakanat A, Wang Y, Do KA, Meric-Bernstam F, Ferrari M (2014) Colocalized delivery of rapamycin and paclitaxel to tumors enhances synergistic targeting of the PI3K/Akt/mTOR pathway. Mol Ther 22:1310–1319