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| Profile Name | ATR inact mut |
| Gene Variant Detail | |
| Relevant Treatment Approaches |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| ATR inact mut | prostate cancer | sensitive | Enzalutamide + Talazoparib | FDA approved | Actionable | In a Phase III trial (TALAPRO-2) that supported FDA approval, Talzenna (talazoparib) plus Xtandi (enzalutamide) improved median radiographic progression-free survival compared to enzalutamide plus placebo (27.9 vs 16.4 mo, HR 0.46, p=0.0003) in patients with metastatic castration-resistant prostate cancer harboring deficient homologous recombination repair genes including ATR, with an HR of 0.66 (p=0.12) in patients with non-BRCA mutations treated with Talzenna (talazoparib) (PMID: 37285865; NCT03395197). | detail... 37285865 | |
| ATR inact mut | prostate cancer | sensitive | Enzalutamide + Talazoparib | Guideline | Actionable | Talzenna (talazoparib) plus Xtandi (enzalutamide) is included in guidelines as systemic therapy for patients with metastatic castration-resistant prostate cancer harboring a pathogenic germline or somatic ATR mutation who have not been treated in the setting of castration-resistant prostate cancer (NCCN.org). | detail... | |
| ATR inact mut | prostate cancer | sensitive | Enzalutamide + Talazoparib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (TALAPRO-3) that supported FDA approval, Talzenna (talazoparib) plus Xtandi (enzalutamide) improved median progression-free survival compared to placebo (77% vs 56%, HR 0.48, p<0.001) in metastatic androgen pathway modulation-sensitive or -naive prostate cancer patients harboring alterations in homologous recombination repair genes as detected by approved assays, including ATR rearrangement, copy number loss, nonsense, frameshift, or splice site variants (PMID: 42223064; NCT04821622). | 42223064 detail... detail... |