Evaluating Immune Checkpoint Blockade in Metastatic Castration-Resistant Prostate Cancers with Deleterious CDK12 Alterations in the Phase 2 IMPACT Trial.
Clin Cancer Res
; 30(15): 3200-3210, 2024 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-38787530
ABSTRACT
PURPOSE:
CDK12 inactivation in metastatic castration-resistant prostate cancer (mCRPC) may predict immunotherapy responses. This phase 2 trial evaluated the efficacy of immune checkpoint inhibitor (ICI) therapy in patients with CDK12-altered mCRPC. PATIENTS ANDMETHODS:
Eligible patients had mCRPC with deleterious CDK12 alterations and any prior therapies except ICI. Cohort A received ipilimumab (1 mg/kg) with nivolumab (3 mg/kg) every 3 weeks for up to four cycles, followed by nivolumab 480 mg every 4 weeks. Cohort C received nivolumab alone 480 mg every 4 weeks. Patients with CDK12-altered nonprostate tumors were enrolled in cohort B and not reported. The primary endpoint was a 50% reduction in PSA (PSA50). Key secondary endpoints included PSA progression-free survival, overall survival, objective response rate, and safety.RESULTS:
PSA was evaluable in 23 patients in cohort A and 14 in cohort C. Median lines of prior therapy were two in cohorts A and C, including any prior novel hormonal agent (74% and 79%) and chemotherapy (57% and 36%). The PSA50 rate was 9% [95% confidence interval (CI), 1%-28%] in cohort A with two responders; neither had microsatellite instability or a tumor mutational burden >10 mutations/megabase. No PSA50 responses occurred in cohort C. Median PSA progression-free survival was 7.0 months (95% CI, 3.6-11.4) in cohort A and 4.5 months (95% CI, 3.4-13.8) in cohort C. Median overall survival was 9.0 months (95% CI, 6.2-12.3) in cohort A and 13.8 months (95% CI, 3.6-not reached) in cohort C.CONCLUSIONS:
There was minimal activity with ICI therapy in patients with CDK12-altered mCRPC.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Quinasas Ciclina-Dependientes
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Neoplasias de la Próstata Resistentes a la Castración
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Inhibidores de Puntos de Control Inmunológico
Límite:
Aged
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Aged80
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Cancer Res
/
Clin. cancer res
/
Clinical cancer research
Asunto de la revista:
NEOPLASIAS
Año:
2024
Tipo del documento:
Article