Authors: Jerome Alexandre, Stephane Oudard, Luca Campedel, Lisa Golmard, Sylvain Ladoire, Ahmed Khalil, Denis Maillet, Christophe Tournigand, Françoise Goirand, Jerome Guitton, Charles Dariane, Florence Joly, Evanguelos Xylinas, Jean Louis Golmard, Hendy Abdoul, Nihel Khoudour, Alicja Puskiel, Edith Carton, Olivier Huillard, Benoit Blanchet
Published: 2023-03-14
DOI: 10.1200/jco.2023.41.6_suppl.159
Source: Full article
159 Background: Abiraterone acetate (ABI) improves survival in mCRPC. In a previous observational study, worse PSA response and shorter progression-free survival (PFS) were associated with mean ABI plasma through concentration (ABI Cmin) < 8.5 ng/mL within the first three months (ms) of treatment (Carton E et al. Eur J Cancer 2017). The OPTIMABI study, a multicenter non-randomized study (NCT 03458247), aimed to investigate whether a dose escalation of ABI improve PFS in underexposed progressive mCRPC pts. Methods: In step 1, pts with docetaxel-naive progressive mCRPC received ABI at the standard dose of 1000 mg/d + Prednisone 10 mg/d. Mean ABI Cmin was calculated from three monthly dosages. Pts experiencing progression within the first 6 ms and for whom mean ABI Cmin was < 8.5 ng/mL were included in step 2 and received 1000 mg twice daily (2000 mg/d) of ABI. ABI Cmin was assessed every month. The primary endpoint was the non-progression rate at 12 weeks in step 2. Identification of risk factors of 6 ms-PFS was done using Cox regression analysis. Results: From 06/2018 to 09/2021, 81 of 93 pts (median age: 72 yrs) included in step 1 were evaluable for statistical analysis. The median ABI Cmin was 10.0 (IQR: 4.5-15. 0) ng/mL over the first three ms. Inter-individual variability was 59%. The 6 ms-PFS was 68% (IC 95%: 56% - 80%) with no statistical difference between pts with mean ABI Cmin ≥ or < 8.5 ng/mL (log-rank test, p= 0.24). In multivariate analysis, liver metastasis (Hazard ratio, HR = 5.95, CI95% = 1.22–28.92; p=0.027) and creatinine clearance < 60 mL/min (HR = 3.51, CI95% = 1.12–10.99; p=0.031) were independently associated with 6 ms-PFS. Among 21 pts (25.9%), with mean ABI Cmin < 8.5 ng/mL, 8 pts (38.1%) experienced tumor progression within the first 6 ms; four of them could be included in step 2. None of them fulfilled the primary endpoint despite a significant increase in plasma ABI Cmin (p <0.036 by paired t-test). Conclusions: Despite high inter-individual variability of mean ABI Cmin, the OPTIMABI study does not support the strategy of intra-individual dose escalation according to plasma concentration of ABI in mCRPC. Underexposure to ABI (ABI Cmin < 8.5 ng/mL) was not statistically associated with shorter PFS. Clinical trial information: NCT03458247 .