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Tumor Response to Bevacizumab Exposure in PROC Patients

August, 08, 2023 | Ovarian Cancer

KEY TAKEAWAYS

  • The phase I PEMBOV trial aimed to develop a pharmacometric model to study the association between bevacizumab exposure and tumor response.
  • A population pharmacodynamic non-linear mixed-effects modeling approach was used to characterize patient tumor size evolution.
  • The study found high bevacizumab exposure correlated with better clinical outcomes in patients with PROC.

There is a high unmet need for disease control in platinum-resistant epithelial ovarian cancer (PROC) patients (pts). Researchers aimed to develop a pharmacometric model to study the association between bevacizumab exposure and tumor response.

The study analyzed tumor growth kinetics using a population pharmacodynamic non-linear mixed-effects modeling approach. The Kkill parameter, measured in week 1, was used to represent the tumor size reduction based on the treatments administered. An Exposure-Response analysis was also conducted to investigate the association between bevacizumab plasma levels (measured as trough levels at the second treatment cycle, PreC2, µg/ml) and the previously determined Kkill parameter.

They found a significant difference in tumor shrinkage rates (Kkill values) between the three cohorts which were cohort A (pembrolizumab plus PLD, n=6, Kkill = 0.00091 week-1), cohort B (pembrolizumab + bevacizumab, n=19, Kkill = 0.002 week-1), and cohort C (pembrolizumab + bevacizumab + PLD, n=19, Kkill = 0.02 week-1). Cohort B and C showed higher tumor shrinkage compared to Cohort A. No clear relationship was observed between bevacizumab plasma levels and tumor shrinkage, but higher bevacizumab exposure was associated with better clinical outcomes (ORR and Stable disease ≥ 4 months) in cohorts B and C.

The study found bevacizumab exposure is correlated with clinical outcomes in PROC patients. Kkill in silico modeling could predict clinical outcomes and help personalize treatments.

Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.3093 

Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03596281

Judith Michels, Mourad Hamimed, Yves Menu, Corinne Balleyguier, François Ghiringhelli, Jean-Sebastien Frenel, Catherine Genestie, Benoit You, Anne Floquet, Lauriane Eberst, Angelo Paci, Rastilav Bahleda, Patricia Pautier, Emeline Colomba, Fanny Pommeret, Alexandra Leary, Aurelien Marabelle, Aurelie Bardet, Caroline Brard, and Joseph Ciccolini. DOI: 10.1200/JCO.2023.41.16_suppl.3093 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 3093-3093.

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