Therapy Detail
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| Therapy Name | Olaparib + Temozolomide |
| Synonyms | |
| Therapy Description | |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| Olaparib | Lynparza | AZD2281|KU-0059436 | PARP Inhibitor (Pan) 19 | Lynparza (olaparib) binds to and inhibits PARP, resulting in inhibition of DNA repair and lethality in homologous-recombination deficient cells, and may be a sensitizing agent for chemotherapy and radiotherapy (PMID: 25028150, PMID: 24225019). Lynparza (olaparib) is FDA approved for treatment of ERBB2 (HER2)-negative breast cancer with deleterious or suspected deleterious germline BRCA mutations, ovarian cancer with deleterious or suspected deleterious germline BRCA mutations and received 3 or more prior therapies, metastatic pancreatic adenocarcinoma with deleterious or suspected deleterious germline BRCA mutations as a maintenance therapy, metastatic castration-resistant prostate cancer with deleterious or suspected deleterious germline or somatic homologous recombination repair gene mutations who progressed following enzalutamide or abiraterone, as a maintenance therapy in recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer and in epithelial ovarian, fallopian tube or primary peritoneal cancer with deleterious or suspected deleterious germline or somatic BRCA mutation, and in combination with Avastin (bevacizumab) as maintenance therapy in HDR defective epithelial ovarian, fallopian tube or primary peritoneal cancer as defined by deleterious or suspected deleterious BRCA mutation, and/or genomic instability (FDA.gov). |
| Temozolomide | Temodar | Methazolastone | Chemotherapy - Alkylating 14 | Temodar (temozolomide) is a dacarbazine analog and cytotoxic alkylating agent (NCI Drug Dictionary). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| Unknown unknown | Ewing sarcoma | not applicable | Olaparib + Temozolomide | Preclinical - Cell culture | Actionable | In a preclinical study, Ewing sarcoma cells treated with Temodar (temozolomide) combined with Lynparza (olaparib) resulted in very strong synergism, inducing apoptosis and reducing cell viability in culture (PMID: 26438158). | 26438158 |
| Unknown unknown | lung small cell carcinoma | not applicable | Olaparib + Temozolomide | Phase Ib/II | Actionable | In a Phase I/II trial, combination of Lynparza (olaparib) and Temodar (temozolomide) resulted in an objective response rate of 41.7% (20/48) in patients with relapsed small cell lung cancer, with a median progression-free survival of 4.2 months and a median overall survival of 8.5 months, similar response was recapitulated in a coclinical trial with 32 patient-derived xenograft models (PMID: 31416802; NCT02446704). | 31416802 |
| Unknown unknown | glioblastoma multiforme | not applicable | Olaparib + Temozolomide | Phase II | Actionable | In a Phase II trial (OPARATIC), 36% (14/39) of evaluable patients with glioblastoma were progression-free at 6 months when treated with the combination therapy of Lynparza (olaparib) and Temodar (temozolomide) (PMID: 32347934; NCT0139057). | 32347934 |
| STAG2 N357fs | glioblastoma multiforme | sensitive | Olaparib + Temozolomide | Preclinical - Cell culture | Actionable | In a preclinical study, glioblastoma cells harboring a STAG2 mutation (reported as STAG2 N357fs, PMID: 21852505) demonstrated increased sensitivity to the combination of Lynparza (olaparib) and Temodar (temozolomide) compared to isogenic cells with wild-type STAG2 in culture (PMID: 24356817). | 21852505 24356817 |
| Unknown unknown | colorectal cancer | not applicable | Olaparib + Temozolomide | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the addition of Lynparza (olaparib) to Temodar (temozolomide) resulted in greater antitumor activity than Temodar (temozolomide) alone in colorectal cancer cell line xenograft models, demonstrating decreased tumor volume (PMID: 27550455). | 27550455 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status |
|---|---|---|---|---|
| NCT03880019 | Phase II | Olaparib + Temozolomide | Olaparib and Temozolomide in Treating Patients With Advanced, Metastatic, or Unresectable Uterine Leiomyosarcoma | Active, not recruiting |
| NCT04166435 | Phase II | Olaparib + Temozolomide | TMZ + Olaparib for MGMT Hypermethylated Colorectal Cancer | Recruiting |
| NCT01858168 | Phase I | Olaparib + Temozolomide | Phase I Study of Olaprib and Temozolomide for Ewings Sarcoma | Recruiting |
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