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Distinct response to platinum-based chemotherapy among patients with metastatic castration-resistant prostate cancer harboring alterations in genes involved in homologous recombination

  • Fan L.,
  • Fei X.C.,
  • Zhu Y.J.,
  • Chi C.F.,
  • Pan J.H.,
  • Sha J.J.,
  • Xin Z.X.,
  • Gong Y.M.,
  • Du X.X.,
  • Wang Y.Q.,
  • Dong B.J.,
  • Xue W.

Introduction & Objectives

To explore the association between genomic status and clinical outcome of platinum-based chemotherapy among patients with metastatic castration resistant prostate cancer (mCRPC).

Materials & Methods

We conducted a retrospective study of 55 patients with mCRPC who received platinum-based chemotherapy after the progression to docetaxel chemotherapy and underwent genomic profiling of 14 homologous recombination (HR) pathway genes. Progression free survival (PFS) were analyzed using Kaplan-Meier method.

Results

Of 55 patients, 23 harbored defects in HR pathway genes. Median PSA-PFS for the HR defect group was 6.7mo compared with 2.6mo for the no HR defect group (p=0.001). The patients harboring somatic HR defect displayed shorter PSA-PFS than those harboring germline HR defect (4.5mo vs. NA;p=0.066). The PSA50 response rate displayed higher in patients harboring BRCA2 or ATM defect(6/8,75.0%) than in those harboring CDK12 defect (2/9,22.2%,p=0.06). Patients harboring BRCA2 or ATM defect displayed prolonged PSA-PFS, compared with those harboring CDK12 defect and those harboring other HR defect (p=0.038). In multivariate Cox regression analysis, HR defect and BRCA2 or ATM defect were independently significant factors associated with superior PFS on platinum-based chemotherapy.

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Conclusions

The patients with mCRPC harboring alterations in different HR genes displayed distinct response to platinum-based chemotherapy. Patients with mCRPC harboring genomic defects in key HR genes either in the germline or somatic, especially BRCA2 and ATM, might have better response to platinum-based chemotherapy. Patients with mCRPC harboring CDK12 defect experienced inferior outcomes to platinum-based chemotherapy compared with those harboring BRCA2 or ATM defect.

Tags: EAU21