Influence of response to prior docetaxel on sensitivity to cabazitaxel in prostate cancer patients with PTEN alterations

• Published in: Cancer science Vol. 113; no. 9; pp. 3161 - 3168
• Main Authors: Kamisawa, Ken, Kosaka, Takeo, Nakamura, Kohei, Yasumizu, Yota, Hongo, Hiroshi, Takeda, Toshikazu, Matsumoto, Kazuhiro, Nishihara, Hiroshi, Oya, Mototsugu
• Format: Journal Article
• Language: English
• Published: Tokyo John Wiley & Sons, Inc 01-09-2022; John Wiley and Sons Inc
• Subjects: Androgens; Antigens; Biopsy; Breast cancer; cabazitaxel; Cancer therapies; Castration; castration‐resistant prostate cancer; Chemotherapy; Chromosome 10; Chromosomes; genetic alteration; Lymphatic system; Medical prognosis; Metastases; Metastasis; Multivariate analysis; Mutation; Original; ORIGINAL ARTICLES; Patients; Phosphatase; Prostate cancer; prostate‐specific antigen response; Proteins; PTEN; PTEN protein; Tensin
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.15473

The purpose of this study was to investigate factors predicting the sensitivity to cabazitaxel therapy in metastatic castration‐resistant prostate cancer (mCRPC) patients with phosphatase and tensin homolog deleted from chromosome 10 (PTEN) alterations. This single‐institution, retrospective study included 12 mCRPC patients with PTEN alterations who had received cabazitaxel therapy. Five patients (41%) responded to cabazitaxel therapy with a prostate‐specific antigen (PSA) level decline of ≥30% from baseline, and all of them had responded to prior docetaxel therapy with a PSA decline of ≥30%. None of the patients with a poor response to prior docetaxel therapy responded well to cabazitaxel therapy. Of the seven patients who did not respond to cabazitaxel and whose PSA declined from baseline was <30%, five (71%) were also refractory to prior docetaxel therapy. The PSA responses to docetaxel and cabazitaxel were significantly correlated (p = 0.027). Kaplan–Meier analysis revealed that progression‐free survival (PFS) for cabazitaxel was significantly shorter for prior docetaxel nonresponders (3.3 versus 9.1 months, p = 0.028). Multivariate analysis revealed that a poor response to prior docetaxel (PSA decline < 30%) (hazard ratio [HR] = 6.382, 95% confidence interval [CI] 1.172–34.750, p = 0.032) and baseline PSA of ≥20 ng/ml (HR = 33.584, 95% CI 2.332–483.671, p = 0.010) were independent prognostic factors for PFS with cabazitaxel therapy. These results demonstrate cross‐resistance between docetaxel and cabazitaxel. The response to prior docetaxel therapy can influence the sensitivity to cabazitaxel therapy in mCRPC patients with PTEN alterations.
This study examined factors that predict sensitivity to cabazitaxel therapy in metastatic castration‐resistant prostate cancer (mCRPC) patients with PTEN alterations. Our study found that a poor response to prior docetaxel therapy was an independent prognostic indicator of progression free survival for cabazitaxel suggesting that prior docetaxel therapy can influence the sensitivity to cabazitaxel therapy.