Pharmacometrics Golems: Exposure-Response Models in Oncology

Akash KhandelwalAna-Marija GrisicJonathan FrenchKarthik Venkatakrishnan. Clin Pharmacol Ther. Published online March 14, 2022. doi:10.1002/cpt.2564

Pharmacometric modeling and machine learning analyses of prognostic and predictive factors in the JAVELIN Gastric 100 phase III trial of avelumab

Terranova NFrench JDai H, et al. CPT Pharmacometrics Syst Pharmacol2022001– 15. doi:10.1002/psp4.12754

Exposure-response analysis of efficacy and safety for pexidartinib in patients with tenosynovial giant cell tumor (TGCT)

Yin O, Zahir H, French J, Polhamus D, Wang X, Van de Sande M, Tap WD, Gelderblom H, Wagner AJ, Healey JH, Greenberg J, Shuster D, Stacchiotti S. CPT: Pharmacometrics & Systems Pharmacology. 2021101422– 1432. doi:10.1002/psp4.12712

Lorlatinib Exposure-Response Analyses for Safety and Efficacy in a Phase I/II Trial to Support Benefit-Risk Assessment in Non-Small Cell Lung Cancer

Chen J, Ruiz-Garcia A, James LP, et al. Clin Pharmacol Ther. 2021;110(5):1273-1281. doi:10.1002/cpt.2228

Population pharmacokinetic model with time-varying clearance for lorlatinib using pooled data from patients with non-small cell lung cancer and healthy participants

Chen J, Houk B, Pithavala YK, Ruiz-Garcia A. CPT Pharmacometrics Syst Pharmacol. 2021 Feb;10(2):148-160. doi: 10.1002/psp4.12585. Epub 2021 Feb 1.

Improving strategic decision-making with early prediction of survival outcomes in oncology clinical trials

Presentation by Jonathan L. French, Sc.D. at 2020 American Conference on Pharmacometrics (ACoP11) virtual meeting. 11 November 2020.

An evaluation of overall survival in patients with newly diagnosed acute myeloid leukemia and the relationship with glasdegib treatment and exposure

Lin S, Shaik N, Chan G, Cortes JE, Ruiz-Garcia A. Cancer Chemother Pharmacol. 2020 Oct;86(4):451-459. doi: 10.1007/s00280-020-04132-x. Epub 2020 Sep 3.

Phase 1 study to evaluate the effect of the investigational anticancer agent sapanisertib on the QTc interval in patients with advanced solid tumors

Patel, Chirag, Sanjay Goel, Manish R. Patel, Lakshmi Rangachari, Jayson D. Wilbur, Yaping Shou, Karthik Venkatakrishnan, and A. Craig Lockhart. Clinical Pharmacology in Drug Development, June 2020.

Population Pharmacokinetic Analysis for Comparison of Pexidartinib Exposure in Asian and Non-Asian Patients

Chia-Chi Lin, Jun Guo, William D. Tap, Andrew J. Wagner, Silvia Stacchiotti, Jih-Hsiang Lee, Xiaoning Wang, Jia Kang, Hamim Zahir, Shun-ichi Sasaki, Ophelia Yin

Poster presented at the 2019 Connective Tissue Oncology Society annual meeting in Toyko, Japan. 14 Nov 2019

Exposure-Response Analysis of Efficacy and Safety for Pexidartinib in Patients With Tenosynovial Giant Cell Tumor (TGCT)

Ophelia Yin, Jonathan French, Daniel Polhamus, Hamim Zahir, Michiel van de Sande, William D. Tap, Hans Gelderblom, Andrew J. Wagner, Jon Greenberg, Dale Shuster, Silvia Stacchiotti

Poster presented at 2019 American Conference on Pharmacometrics (ACoP10) in Orlando, FL. 23 October 2019.

A Semi-physiological Population Pharmacokinetic Model Developed Using Clinical Dose Escalation and Dose Confirmation Data for an Oral Fixed-Dose Combination of CDA Inhibitor Cedazuridine with Decitabine (ASTX727) in Subjects with Myelodysplastic Syndromes

Eric Burroughs Jordie, Ahmed Elmokadem, Mohammad Azab, and Aram Oganesian

Presented by Eric Jordie at American Conference on Pharmacometrics 2019.

Population Pharmacokinetic Analysis of Pexidartinib in Healthy Subjects and Patients with Tenosynovial Giant Cell Tumor (TGCT) or Other Solid Tumors

Ophelia Yin, Jia Kang, William Knebel, Hamim Zahir, Michiel van de Sande, William D. Tap, Hans Gelderblom, Silvia Stacchiotti, Jon Greenberg, Dale Shuster, Andrew J. Wagner

Poster presented at 2019 American Conference on Pharmacometrics (ACoP10) in Orlando, FL. 21 October 2019.

Pharmacokinetics of trastuzumab emtansine (T-DM1) as a single agent or in combination with pertuzumab in HER2-positive breast cancer patients with recurrent or locally advanced metastatic breast cancer

Lu D, Li C, Riggs M, Polhamus D, French J, Agarwal P, Chen S-C, Vadhavkar S, Patre M, Strasak A, Quartino A, Jin JY, Girish S. Cancer Chemother Pharmacol [Internet]. 2019 May 17. doi: 10.1007/s00280-019-03852-z.

Exposure–response analyses of trastuzumab emtansine in patients with HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane

Li C, Wang B, Chen SC, Wada R, Lu D, Wang X, Polhamus D, French J, Vadhavkar S, Strasak A, Smitt M, Joshi A, Samant M, Quartino A, Jin J, Girish S. Cancer Chemotherapy and Pharmacology 80 (6): 1079–90. December 2017.

Modeling methods for analyzing tumor dynamic data from basket trials

Ocampo-Pelland AS, French JL.  Presented at the 8th American Conference on Pharmacometrics (ACoP), Fort Lauderdale, FL, October 2017.

Population pharmacokinetics and exposure–response of trastuzumab emtansine in advanced breast cancer previously treated with ≥2 HER2-targeted regimens

Chen S-C, Quartino A, Polhamus D, Riggs M, French J, Wang X, Vadhavkar S, Smitt M, Hoersch S, Strasak A, Jin JY, Girish S, and Li C. Br J Clin Pharmacol, 2017 Jul 21.

Population pharmacokinetic modeling of intravenous asparaginase erwinia chrysanthemi: Impact of varied infusion rates on exposure

Zomorodi K, Dumas T, Berry S, Johnston C, and Eller M. 

Population pharmacokinetics (PK) and exposure-response (E-R) analysis of trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer (MBC) who have received at least two prior regimens of HER2-directed therapy

Chen SC, Quartino AL, Polhamus D, Riggs MM, French JL, Wang X, Vadhavkar S, Smitt M, Hoersch S, Strasak A, Chernyukhin N, Jin JY, Girish S, Li C.  Abstract in Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Cancer Res 2017;77(4 Suppl):Abstract P4-21-26.

Pharmacokinetics (PK) and exposure-response (E-R) analysis of Kadcyla (K) as a single agent or in combination with Perjeta (P) in patients with human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer (MBC) who have not received prior chemotherapy for their metastatic disease

Lu D, Li C, Polhamus D, French JL, Riggs MM, Agarwal P, Chen SC, Wang X, Smitt M, Patre M, Strasak A, ChernyukhinN , Quartino AL, Jin JY, Girish S.  Presented at the 7th American Conference on Pharmacometrics (ACoP), Bellevue, WA; October 2016.

Comparisons of multiple exposure-response methodologies in oncology.

Polhamus D, French J, Chen SC, Wang B, Li C, Lu D, Girish S, Jin J, Quartino A.  Presented at the Annual Meeting of the Population Approach Group in Europe (PAGE), Lisboa, June 2016.

A modeling and simulation framework for exposure-response analysis in oncology: comparison and considerations of multiple methodologies

Polhamus D, French J, Chen S-C, Wang B, Li C, Lu D, Girish S, Jin J, Quartino A.  Presented at the 6th American Conference on Pharmacometrics, Arlington, VA; October 2015.

Exposure-response modeling in oncology: technical challenges and proposed solutions

Jonathan French. Presented at the 5th American Conference on Pharmacometrics (ACoP), Las Vegas, NV, October 2014.

PKPD modeling of predictors for adverse effects and overall survival in sunitinib-treated patients with GIST

Hansson EK, Ma G, Amantea MA, French J, Milligan PA, Friberg LE, and Karlsson MO. CPT: Pharmacometrics & Systems Pharmacology. 2013;2(12):e85-. doi:10.1038/psp.2013.62.

PKPD modeling of VEGF, sVEGFR-2, sVEGFR-3, and sKIT as predictors of tumor dynamics and overall survival following sunitinib treatment in GIST

Hansson EK, Amantea MA, Westwood P, Milligan PA, Houk BE, French J, Karlsson MO and Friberg LE. CPT: Pharmacometrics & Systems Pharmacology. 2013;2(11):e84-. doi:10.1038/psp.2013.61

Can methods based on existing models really aid decision making in non-small-cell lung cancer (NSCLC) trials?

Presented at the Annual Meeting of the Population Approach Group Europe (PAGE), Glasgow; June, 2013. Abstract A-06.

Opportunities and challenges of MBMA in oncology

French J. Presented at the 4th American Conference on Pharmacometrics (ACoP), Ft. Lauderdale; May 2013.