Skip to main content
Erschienen in: Cancer Chemotherapy and Pharmacology 4/2014

01.10.2014 | Original Article

Population pharmacokinetic and covariate analysis of pertuzumab, a HER2-targeted monoclonal antibody, and evaluation of a fixed, non-weight-based dose in patients with a variety of solid tumors

verfasst von: Amit Garg, Angelica Quartino, Jing Li, Jin Jin, D. Russell Wada, Hanbin Li, Javier Cortés, Virginia McNally, Graham Ross, Jennifer Visich, Bert Lum

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 4/2014

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To characterize the population pharmacokinetics (PK) of pertuzumab across clinical trials in a variety of solid tumors, evaluate the potential impact of patient characteristics on PK, and confirm the appropriateness of the fixed (non-weight-based) dose.

Methods

Pertuzumab concentration data collected following intravenous administration during eleven phase I/II studies and the pivotal phase III trial CLEOPATRA were analyzed using nonlinear mixed-effects modeling. The potential impact of patient and laboratory characteristics and HER2 target-related variables on pertuzumab PK were investigated in a covariate analysis. The final model was used to confirm selection of fixed, non-weight-based dosing of pertuzumab, and to compare pertuzumab PK in CLEOPATRA with the other studies.

Results

The analysis included 4,525 serum concentration measurements from 481 patients with solid tumors. Pertuzumab PK in the 2–25 mg/kg dose range was described by a two-compartment linear model with first-order elimination. The elimination clearance and central compartment volume were 0.235 L/day, and 3.11 L, respectively, and the terminal elimination half-life was 18.0 days. Baseline serum albumin and lean body weight had statistically significant effects on pertuzumab clearance; however, simulations showed that the magnitude of their effects on pertuzumab exposure was minimal compared with overall variability and was not clinically relevant. Thus, variations in these factors do not require dose adjustments.

Conclusions

The fixed, non-weight-based dosing of pertuzumab, 840 mg loading dose followed by a 420 mg maintenance dose every 3 weeks, in patients with the solid tumors in this analysis is well supported by the population pharmacokinetic modeling and simulation results.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Agus DB, Akita RW, Fox WD, Lewis GD, Higgins B, Pisacane PI, Lofgren JA, Tindell C, Evans DP, Maiese K, Scher HI, Sliwkowski MX (2002) Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth. Cancer Cell 2:127–137PubMedCrossRef Agus DB, Akita RW, Fox WD, Lewis GD, Higgins B, Pisacane PI, Lofgren JA, Tindell C, Evans DP, Maiese K, Scher HI, Sliwkowski MX (2002) Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth. Cancer Cell 2:127–137PubMedCrossRef
2.
Zurück zum Zitat Junttila TT, Akita RW, Parsons K, Fields C, Lewis Phillips GD, Friedman LS, Sampath D, Sliwkowski MX (2009) Ligand-independent HER2/HER3/PI3 K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell 15:429–440PubMedCrossRef Junttila TT, Akita RW, Parsons K, Fields C, Lewis Phillips GD, Friedman LS, Sampath D, Sliwkowski MX (2009) Ligand-independent HER2/HER3/PI3 K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell 15:429–440PubMedCrossRef
3.
Zurück zum Zitat Cho HS, Mason K, Ramyar KX, Stanley AM, Gabelli SB, Denney DW Jr, Leahy DJ (2003) Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 421:756–760PubMedCrossRef Cho HS, Mason K, Ramyar KX, Stanley AM, Gabelli SB, Denney DW Jr, Leahy DJ (2003) Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 421:756–760PubMedCrossRef
4.
Zurück zum Zitat Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX (2004) Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell 5:317–328PubMedCrossRef Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX (2004) Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell 5:317–328PubMedCrossRef
5.
Zurück zum Zitat Scheuer W, Friess T, Burtscher H, Bossenmaier B, Endl J, Hasmann M (2009) Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res 69:9330–9336PubMedCrossRef Scheuer W, Friess T, Burtscher H, Bossenmaier B, Endl J, Hasmann M (2009) Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res 69:9330–9336PubMedCrossRef
6.
Zurück zum Zitat Agus DB, Gordon MS, Taylor C, Natale RB, Karlan B, Mendelson DS, Press MF, Allison DE, Sliwkowski MX, Lieberman G, Kelsey SM, Fyfe G (2005) Phase I clinical study of pertuzumab, a novel HER dimerization inhibitor, in patients with advanced cancer. J Clin Oncol 23:2534–2543PubMedCrossRef Agus DB, Gordon MS, Taylor C, Natale RB, Karlan B, Mendelson DS, Press MF, Allison DE, Sliwkowski MX, Lieberman G, Kelsey SM, Fyfe G (2005) Phase I clinical study of pertuzumab, a novel HER dimerization inhibitor, in patients with advanced cancer. J Clin Oncol 23:2534–2543PubMedCrossRef
7.
Zurück zum Zitat Agus DB, Sweeney CJ, Morris MJ, Mendelson DS, McNeel DG, Ahmann FR, Wang J, Derynck MK, Ng K, Lyons B, Allison DE, Kattan MW, Scher HI (2007) Efficacy and safety of single-agent pertuzumab (rhuMAb 2C4), a human epidermal growth factor receptor dimerization inhibitor, in castration-resistant prostate cancer after progression from taxane-based therapy. J Clin Oncol 25:675–681PubMedCrossRef Agus DB, Sweeney CJ, Morris MJ, Mendelson DS, McNeel DG, Ahmann FR, Wang J, Derynck MK, Ng K, Lyons B, Allison DE, Kattan MW, Scher HI (2007) Efficacy and safety of single-agent pertuzumab (rhuMAb 2C4), a human epidermal growth factor receptor dimerization inhibitor, in castration-resistant prostate cancer after progression from taxane-based therapy. J Clin Oncol 25:675–681PubMedCrossRef
8.
Zurück zum Zitat de Bono JS, Bellmunt J, Attard G, Droz JP, Miller K, Flechon A, Sternberg C, Parker C, Zugmaier G, Hersberger-Gimenez V, Cockey L, Mason M, Graham J (2007) Open-label phase II study evaluating the efficacy and safety of two doses of pertuzumab in castrate chemotherapy-naive patients with hormone-refractory prostate cancer. J Clin Oncol 25:257–262PubMedCrossRef de Bono JS, Bellmunt J, Attard G, Droz JP, Miller K, Flechon A, Sternberg C, Parker C, Zugmaier G, Hersberger-Gimenez V, Cockey L, Mason M, Graham J (2007) Open-label phase II study evaluating the efficacy and safety of two doses of pertuzumab in castrate chemotherapy-naive patients with hormone-refractory prostate cancer. J Clin Oncol 25:257–262PubMedCrossRef
9.
Zurück zum Zitat Herbst RS, Davies AM, Natale RB, Dang TP, Schiller JH, Garland LL, Miller VA, Mendelson D, Van den Abbeele AD, Melenevsky Y, de Vries DJ, Eberhard DA, Lyons B, Lutzker SG, Johnson BE (2007) Efficacy and safety of single-agent pertuzumab, a human epidermal receptor dimerization inhibitor, in patients with non small cell lung cancer. Clin Cancer Res 13:6175–6181PubMedCrossRef Herbst RS, Davies AM, Natale RB, Dang TP, Schiller JH, Garland LL, Miller VA, Mendelson D, Van den Abbeele AD, Melenevsky Y, de Vries DJ, Eberhard DA, Lyons B, Lutzker SG, Johnson BE (2007) Efficacy and safety of single-agent pertuzumab, a human epidermal receptor dimerization inhibitor, in patients with non small cell lung cancer. Clin Cancer Res 13:6175–6181PubMedCrossRef
10.
Zurück zum Zitat Gordon MS, Matei D, Aghajanian C, Matulonis UA, Brewer M, Fleming GF, Hainsworth JD, Garcia AA, Pegram MD, Schilder RJ (2006) Clinical activity of pertuzumab (rhuMAb 2C4), a HER dimerization inhibitor, in advanced ovarian cancer: potential predictive relationship with tumor HER2 activation status. J Clin Oncol 24:4324–4332PubMedCrossRef Gordon MS, Matei D, Aghajanian C, Matulonis UA, Brewer M, Fleming GF, Hainsworth JD, Garcia AA, Pegram MD, Schilder RJ (2006) Clinical activity of pertuzumab (rhuMAb 2C4), a HER dimerization inhibitor, in advanced ovarian cancer: potential predictive relationship with tumor HER2 activation status. J Clin Oncol 24:4324–4332PubMedCrossRef
11.
Zurück zum Zitat Gianni L, Llado A, Bianchi G, Cortes J, Kellokumpu-Lehtinen PL, Cameron DA, Miles D, Salvagni S, Wardley A, Goeminne JC, Hersberger V, Baselga J (2010) Open-label, phase II, multicenter, randomized study of the efficacy and safety of two dose levels of pertuzumab, a human epidermal growth factor receptor 2 dimerization inhibitor, in patients with human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol 28:1131–1137PubMedCrossRef Gianni L, Llado A, Bianchi G, Cortes J, Kellokumpu-Lehtinen PL, Cameron DA, Miles D, Salvagni S, Wardley A, Goeminne JC, Hersberger V, Baselga J (2010) Open-label, phase II, multicenter, randomized study of the efficacy and safety of two dose levels of pertuzumab, a human epidermal growth factor receptor 2 dimerization inhibitor, in patients with human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol 28:1131–1137PubMedCrossRef
12.
Zurück zum Zitat Yamamoto N, Yamada Y, Fujiwara Y, Yamada K, Fujisaka Y, Shimizu T, Tamura T (2009) Phase I and pharmacokinetic study of HER2-targeted rhuMAb 2C4 (Pertuzumab, RO4368451) in Japanese patients with solid tumors. Jpn J Clin Oncol 39(260–266):17 Yamamoto N, Yamada Y, Fujiwara Y, Yamada K, Fujisaka Y, Shimizu T, Tamura T (2009) Phase I and pharmacokinetic study of HER2-targeted rhuMAb 2C4 (Pertuzumab, RO4368451) in Japanese patients with solid tumors. Jpn J Clin Oncol 39(260–266):17
13.
Zurück zum Zitat Albanell J, Montagut C, Jones ET, Pronk L, Mellado B, Beech J, Gascon P, Zugmaier G, Brewster M, Saunders MP, Valle JW (2008) A phase I study of the safety and pharmacokinetics of the combination of pertuzumab (rhuMab 2C4) and capecitabine in patients with advanced solid tumors. Clin Cancer Res 14:2726–2731PubMedCrossRef Albanell J, Montagut C, Jones ET, Pronk L, Mellado B, Beech J, Gascon P, Zugmaier G, Brewster M, Saunders MP, Valle JW (2008) A phase I study of the safety and pharmacokinetics of the combination of pertuzumab (rhuMab 2C4) and capecitabine in patients with advanced solid tumors. Clin Cancer Res 14:2726–2731PubMedCrossRef
14.
Zurück zum Zitat Attard G, Kitzen J, Blagden SP, Fong PC, Pronk LC, Zhi J, Zugmaier G, Verweij J, de Bono JS, de Jonge M (2007) A phase Ib study of pertuzumab, a recombinant humanised antibody to HER2, and docetaxel in patients with advanced solid tumours. Br J Cancer 97:1338–1343PubMedCrossRefPubMedCentral Attard G, Kitzen J, Blagden SP, Fong PC, Pronk LC, Zhi J, Zugmaier G, Verweij J, de Bono JS, de Jonge M (2007) A phase Ib study of pertuzumab, a recombinant humanised antibody to HER2, and docetaxel in patients with advanced solid tumours. Br J Cancer 97:1338–1343PubMedCrossRefPubMedCentral
15.
Zurück zum Zitat Felip E, Ranson M, Cedrés S, Dean E, Brewster M, Martinez P, McNally V, Ross G, Galdermans D (2012) A phase Ib, dose-finding study of erlotinib in combination with a fixed dose of pertuzumab in patients with advanced non-small-cell lung cancer. Clin Lung Cancer 13:432–441PubMedCrossRef Felip E, Ranson M, Cedrés S, Dean E, Brewster M, Martinez P, McNally V, Ross G, Galdermans D (2012) A phase Ib, dose-finding study of erlotinib in combination with a fixed dose of pertuzumab in patients with advanced non-small-cell lung cancer. Clin Lung Cancer 13:432–441PubMedCrossRef
16.
Zurück zum Zitat Makhija S, Amler LC, Glenn D, Ueland FR, Gold MA, Dizon DS, Paton V, Lin CY, Januario T, Ng K, Strauss A, Kelsey S, Sliwkowski MX, Matulonis U (2010) Clinical activity of gemcitabine plus pertuzumab in platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. J Clin Oncol 28:1215–1223PubMedCrossRef Makhija S, Amler LC, Glenn D, Ueland FR, Gold MA, Dizon DS, Paton V, Lin CY, Januario T, Ng K, Strauss A, Kelsey S, Sliwkowski MX, Matulonis U (2010) Clinical activity of gemcitabine plus pertuzumab in platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. J Clin Oncol 28:1215–1223PubMedCrossRef
17.
Zurück zum Zitat Kaye SB, Poole CJ, Dańska-Bidzińska A, Gianni L, Del Conte G, Gorbunova V, Novikova E, Strauss A, Moczko M, McNally VA, Ross G, Vergote I (2013) A randomized phase II study evaluating the combination of carboplatin-based chemotherapy with pertuzumab versus carboplatin-based therapy alone in patients with relapsed, platinum-sensitive ovarian cancer. Ann Oncol 24:145–152PubMedCrossRef Kaye SB, Poole CJ, Dańska-Bidzińska A, Gianni L, Del Conte G, Gorbunova V, Novikova E, Strauss A, Moczko M, McNally VA, Ross G, Vergote I (2013) A randomized phase II study evaluating the combination of carboplatin-based chemotherapy with pertuzumab versus carboplatin-based therapy alone in patients with relapsed, platinum-sensitive ovarian cancer. Ann Oncol 24:145–152PubMedCrossRef
18.
Zurück zum Zitat Portera CC, Walshe JM, Rosing DR, Denduluri N, Berman AW, Vatas U, Velarde M, Chow CK, Steinberg SM, Nguyen D, Yang SX, Swain SM (2008) Cardiac toxicity and efficacy of trastuzumab combined with pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. Clin Cancer Res 14:2710–2716PubMedCrossRef Portera CC, Walshe JM, Rosing DR, Denduluri N, Berman AW, Vatas U, Velarde M, Chow CK, Steinberg SM, Nguyen D, Yang SX, Swain SM (2008) Cardiac toxicity and efficacy of trastuzumab combined with pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. Clin Cancer Res 14:2710–2716PubMedCrossRef
19.
Zurück zum Zitat Baselga J, Gelmon KA, Verma S, Wardley A, Conte P, Miles D, Bianchi G, Cortes J, McNally VA, Ross GA, Fumoleau P, Gianni L (2010) Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy. J Clin Oncol 28:1138–1144PubMedCrossRef Baselga J, Gelmon KA, Verma S, Wardley A, Conte P, Miles D, Bianchi G, Cortes J, McNally VA, Ross GA, Fumoleau P, Gianni L (2010) Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy. J Clin Oncol 28:1138–1144PubMedCrossRef
20.
Zurück zum Zitat Cortés J, Fumoleau P, Bianchi GV, Petrella TM, Gelmon K, Pivot X, Verma S, Albanell J, Conte P, Lluch A, Salvagni S, Servent V, Gianni L, Scaltriti M, Ross GA, Dixon J, Szado T, Baselga J (2012) Pertuzumab monotherapy after trastuzumab-based treatment and subsequent reintroduction of trastuzumab: activity and tolerability in patients with advanced human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 30:1594–1600PubMedCrossRef Cortés J, Fumoleau P, Bianchi GV, Petrella TM, Gelmon K, Pivot X, Verma S, Albanell J, Conte P, Lluch A, Salvagni S, Servent V, Gianni L, Scaltriti M, Ross GA, Dixon J, Szado T, Baselga J (2012) Pertuzumab monotherapy after trastuzumab-based treatment and subsequent reintroduction of trastuzumab: activity and tolerability in patients with advanced human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 30:1594–1600PubMedCrossRef
21.
Zurück zum Zitat 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) CLEOPATRA study group pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 366:109–119PubMedCrossRef 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) CLEOPATRA study group pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 366:109–119PubMedCrossRef
22.
Zurück zum Zitat Swain SM, Kim S, Cortés J, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero J, 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 14:461–471PubMedCrossRefPubMedCentral Swain SM, Kim S, Cortés J, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero J, 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 14:461–471PubMedCrossRefPubMedCentral
23.
Zurück zum Zitat Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi G, Szado T, Ratnayake J, Ross G, Valagussa P (2012) Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 13:25–32PubMedCrossRef Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi G, Szado T, Ratnayake J, Ross G, Valagussa P (2012) Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 13:25–32PubMedCrossRef
24.
Zurück zum Zitat Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai Y-F, Ratnayake J, McNally V, Ross G, Cortés J (2013) Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 24:2278–2284PubMedCrossRef Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai Y-F, Ratnayake J, McNally V, Ross G, Cortés J (2013) Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 24:2278–2284PubMedCrossRef
25.
Zurück zum Zitat Ng CM, Lum BL, Gimenez V, Kelsey S, Allison D (2006) Rationale for fixed dosing of pertuzumab in cancer patients based on population pharmacokinetic analysis. Pharm Res 23:1275–1284PubMedCrossRef Ng CM, Lum BL, Gimenez V, Kelsey S, Allison D (2006) Rationale for fixed dosing of pertuzumab in cancer patients based on population pharmacokinetic analysis. Pharm Res 23:1275–1284PubMedCrossRef
26.
Zurück zum Zitat Keizer RJ, Huitema AD, Schellens JH, Beijnen JH (2010) Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet 49:493–507PubMedCrossRef Keizer RJ, Huitema AD, Schellens JH, Beijnen JH (2010) Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet 49:493–507PubMedCrossRef
27.
Zurück zum Zitat Mandema JW, Verotta D, Sheiner LB (1992) Building population pharmacokinetic–pharmacodynamic models. I. Models for covariate effects. J Pharmacokinet Biopharm 20:511–528PubMedCrossRef Mandema JW, Verotta D, Sheiner LB (1992) Building population pharmacokinetic–pharmacodynamic models. I. Models for covariate effects. J Pharmacokinet Biopharm 20:511–528PubMedCrossRef
28.
29.
Zurück zum Zitat Malik MA, Totpal K, Balter I, Sliwkowski MX, Pelletier N, Reich M, Crocker L, Friess T, Bauer S, Fiebig HH, Allison DE (2003) Dose response studies of recombinant humanized monoclonal antibody 2C4 in tumor xenograft models. Proc Am Assoc Cancer Res 44:150 Malik MA, Totpal K, Balter I, Sliwkowski MX, Pelletier N, Reich M, Crocker L, Friess T, Bauer S, Fiebig HH, Allison DE (2003) Dose response studies of recombinant humanized monoclonal antibody 2C4 in tumor xenograft models. Proc Am Assoc Cancer Res 44:150
30.
Zurück zum Zitat Mould DR, Sweeney KR (2007) The pharmacokinetics and pharmacodynamics of monoclonal antibodies–mechanistic modeling applied to drug development. Curr Opin Drug Discov Devel 10:84–96PubMed Mould DR, Sweeney KR (2007) The pharmacokinetics and pharmacodynamics of monoclonal antibodies–mechanistic modeling applied to drug development. Curr Opin Drug Discov Devel 10:84–96PubMed
31.
Zurück zum Zitat Bruno R, Washington CB, Lu JF, Lieberman G, Banken L, Klein P (2005) Population pharmacokinetics of trastuzumab in patients with HER2 + metastatic breast cancer. Cancer Chemother Pharmacol 56:361–369PubMedCrossRef Bruno R, Washington CB, Lu JF, Lieberman G, Banken L, Klein P (2005) Population pharmacokinetics of trastuzumab in patients with HER2 + metastatic breast cancer. Cancer Chemother Pharmacol 56:361–369PubMedCrossRef
32.
Zurück zum Zitat Kang Y, Rha SY, Tassone P, Barriuso J, Yu R, Szado T, Garg A, Bang Y (2013) Pertuzumab pharmacokinetics and safety in combination with trastuzumab and chemotherapy in patients with HER2-positive advanced gastric cancer (AGC). Ann Oncol 24:iv19 Kang Y, Rha SY, Tassone P, Barriuso J, Yu R, Szado T, Garg A, Bang Y (2013) Pertuzumab pharmacokinetics and safety in combination with trastuzumab and chemotherapy in patients with HER2-positive advanced gastric cancer (AGC). Ann Oncol 24:iv19
33.
Zurück zum Zitat Cortes J, Swain SM, Kudaba I, Hauschild M, Patel T, Grincuka E, Masuda N, McNally V, Ross G, Brewster M, Marier JF, Trinh MM, Garg A, Nijem I, Visich J, Lum BL, Baselga J (2013) Absence of pharmacokinetic drug–drug interaction of pertuzumab with trastuzumab and docetaxel. Anticancer Drugs 24:1084–1092PubMedCrossRef Cortes J, Swain SM, Kudaba I, Hauschild M, Patel T, Grincuka E, Masuda N, McNally V, Ross G, Brewster M, Marier JF, Trinh MM, Garg A, Nijem I, Visich J, Lum BL, Baselga J (2013) Absence of pharmacokinetic drug–drug interaction of pertuzumab with trastuzumab and docetaxel. Anticancer Drugs 24:1084–1092PubMedCrossRef
34.
Zurück zum Zitat Wang DD, Zhang S, Zhao H, Men AY, Parivar K (2009) Fixed dosing versus body size-based dosing of monoclonal antibodies in adult clinical trials. J Clin Pharmacol 49:1012–1024PubMedCrossRef Wang DD, Zhang S, Zhao H, Men AY, Parivar K (2009) Fixed dosing versus body size-based dosing of monoclonal antibodies in adult clinical trials. J Clin Pharmacol 49:1012–1024PubMedCrossRef
35.
Zurück zum Zitat Bai S, Jorga K, Xin Y, Jin D, Zheng Y, Damico-Beyer LA, Gupta M, Tang M, Allison DE, Lu D, Zhang Y, Joshi A, Dresser MJ (2012) A guide to rational dosing of monoclonal antibodies. Clin Pharmacokinet 51:119–135PubMedCrossRef Bai S, Jorga K, Xin Y, Jin D, Zheng Y, Damico-Beyer LA, Gupta M, Tang M, Allison DE, Lu D, Zhang Y, Joshi A, Dresser MJ (2012) A guide to rational dosing of monoclonal antibodies. Clin Pharmacokinet 51:119–135PubMedCrossRef
36.
Zurück zum Zitat Fasanmade AA, Adedokun OJ, Olson A, Strauss R, Davis HM (2010) Serum albumin concentration: a predictive factor of infliximab pharmacokinetics and clinical response in patients with ulcerative colitis. Int J Clin Pharmacol Ther 48:297–308PubMedCrossRef Fasanmade AA, Adedokun OJ, Olson A, Strauss R, Davis HM (2010) Serum albumin concentration: a predictive factor of infliximab pharmacokinetics and clinical response in patients with ulcerative colitis. Int J Clin Pharmacol Ther 48:297–308PubMedCrossRef
37.
Zurück zum Zitat Kim J, Bronson CL, Hayton WL, Radmacher MD, Roopenian DC, Robinson JM, Anderson CL (2006) Albumin turnover: FcRn-mediated recycling saves as much albumin from degradation as the liver produces. Am J Physiol Gastrointest Liver Physiol 290:G352–G360PubMedCrossRef Kim J, Bronson CL, Hayton WL, Radmacher MD, Roopenian DC, Robinson JM, Anderson CL (2006) Albumin turnover: FcRn-mediated recycling saves as much albumin from degradation as the liver produces. Am J Physiol Gastrointest Liver Physiol 290:G352–G360PubMedCrossRef
38.
Zurück zum Zitat Kim J, Hayton WL, Robinson JM, Anderson CL (2007) Kinetics of FcRn-mediated recycling of IgG and albumin in human: pathophysiology and therapeutic implications using a simplified mechanism-based model. Clin Immunol 122:146–155PubMedCrossRefPubMedCentral Kim J, Hayton WL, Robinson JM, Anderson CL (2007) Kinetics of FcRn-mediated recycling of IgG and albumin in human: pathophysiology and therapeutic implications using a simplified mechanism-based model. Clin Immunol 122:146–155PubMedCrossRefPubMedCentral
39.
Zurück zum Zitat Allin KH, Nordestgaard BG, Flyger H, Bojesen SE (2011) Elevated pre-treatment levels of plasma C-reactive protein are associated with poor prognosis after breast cancer: a cohort study. Breast Cancer Res 13(R55):19 Allin KH, Nordestgaard BG, Flyger H, Bojesen SE (2011) Elevated pre-treatment levels of plasma C-reactive protein are associated with poor prognosis after breast cancer: a cohort study. Breast Cancer Res 13(R55):19
40.
Zurück zum Zitat Xu Z, Vu T, Lee H, Hu C, Ling J, Yan H, Baker D, Beutler A, Pendley C, Wagner C, Davis HM, Zhou H (2009) Population pharmacokinetics of golimumab, an anti-tumor necrosis factor-alpha human monoclonal antibody, in patients with psoriatic arthritis. J Clin Pharmacol 49:1056–1070PubMedCrossRef Xu Z, Vu T, Lee H, Hu C, Ling J, Yan H, Baker D, Beutler A, Pendley C, Wagner C, Davis HM, Zhou H (2009) Population pharmacokinetics of golimumab, an anti-tumor necrosis factor-alpha human monoclonal antibody, in patients with psoriatic arthritis. J Clin Pharmacol 49:1056–1070PubMedCrossRef
Metadaten
Titel
Population pharmacokinetic and covariate analysis of pertuzumab, a HER2-targeted monoclonal antibody, and evaluation of a fixed, non-weight-based dose in patients with a variety of solid tumors
verfasst von
Amit Garg
Angelica Quartino
Jing Li
Jin Jin
D. Russell Wada
Hanbin Li
Javier Cortés
Virginia McNally
Graham Ross
Jennifer Visich
Bert Lum
Publikationsdatum
01.10.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 4/2014
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-014-2560-3

Weitere Artikel der Ausgabe 4/2014

Cancer Chemotherapy and Pharmacology 4/2014 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.