| General information |
| Database: | DB00523 |
| Objective: | laparib (AZD2281) is a smallmolecule, potent oral poly(ADPribose) polymerase (PARP) inhibitor. they aimed to assess the safety and tolerability of this drug in patients without BRCA1 or BRCA2 mutations with advanced triplenegative breast cancer or highgrade serous and/or undifferentiated ovarian cancer. |
| Authors: | Gelmon KA, et al |
| Title: | Olaparib in patients with recurrent highgrade serous or poorly differentiated ovarian carcinoma or triplenegative breast cancer: a phase 2, multicentre, openlabel, nonrandomised study. |
| Journal: | Lancet Oncol. |
| Year: | 2011 |
| PMID: | 21862407 |
| Trial Design |
| Clinical Trial Id: | NCT00679783 |
| Agent: | olaparib
|
| Target: | Poly [ADPribose] polymerase1
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | advanced triplenegative breast cancer or highgrade serous and/or undifferentiated ovarian cancer without BRCA1 or BRCA2 mutations |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase II, multicentre, openlabel, nonrandomised study |
| Key Patients Feature: | Patientsaged 18 years or older were enrolled if they hadhistologically confirmed advanced metastatic or recurrentbreast cancer (oestrogenreceptor, progesteronereceptor, or human epidermal growth factor receptor 2 negative, or known BRCAmutated breastcancer) or ovarian cancer (highgrade serous and/orundifferentiated and/or known BRCAmutated ovarianand/or fallopiantube or peritoneum cancer), a lifeexpectancy of 16 weeks or more, an Eastern CooperativeGroup (ECOG) performance status of 2 or less, acceptablehaemoglobin concentrations (more than and equal to 90 g/L), haematological(absolute neutrophil count more than and equal to 1500¡Á10 cells per L, whitebloodcell count >3¡Á10 cells per L, platelet countmore than and equal to 100 000 cells per ¦ÌL), hepatic (total bilirubin levels less than and equal to 1.5times normal [<3 times upper limit of normal for patients with Gilbert¡¯s syndrome], aspartate aminotransferase and alanine aminotransferase concen trationsless than and equal to 2.5 times normal [less than and equal to 5 times upper limit of normal forpatients with liver metastases]), and renal function(serum creatinine concentration of less than and equal to 1.5 times normal), and had been tested or were willing to undergo BRCA1and BRCA2 mutation testing by the external ref |
| Biomarker: | BRCA1 or BRCA2 mutation |
| Biomark Analysis: | In these patients, confirmed objective responses were seen in seven (41%; 95% CI 2264) of 17 patients with BRCA1 or BRCA2 mutations and 11 (24%; 1438) of 46 without mutations. No confirmed objective responses were reported in patients with breast cancer. |
| Control Group Info: | single arm |
| Treatment Info: | pts were enrolled and received olaparib 400 mg twice a day. Patients were stratified according to whether they had a BRCA1 or BRCA2 mutation or not. |
| Primary End Point: | objective response rate |
| Secondary End Point: | the analysis of toxic effects, and patients who had measurable lesions at baseline were included in the primary efficacy analysis. |
| Patients Number: | 91 |
| Trial Results |
| DLT_MTD: | The most commonadverse events were fatigue (45 [70%] of patients with ovarian cancer, 13 [50%] of patients with breast cancer), nausea(42 [66%] and 16 [62%]), vomiting (25 [39%] and nine [35%]), and decreased appetite (23 [36%] and seven [27%]). |
| Objective Response Rate: | 63 patients had target lesionsand therefore were evaluable for objective response as per RECIST. In these patients, confi rmed objective responseswere seen in seven (41%; 95% CI 22-64) of 17 patients with BRCA1 or BRCA2 mutations and 11 (24%; 14-38) of 46without mutations. No confi rmed objective responses were reported in patients with breast cancer |
| Disease Control Rate: | in BRCA1 or BRCA2 negative mutation cohorts the diseasecontrol rate was 76% (13 of 17) and in BRCA1 or BRCA2 positive cohorts it was 62% (29 of 47). |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | In the ovariancancer cohort, median progression free survival (assessed by RECIST) in patients with BRCA mutation was 221 (95% CI 106-383) days, in those without BRCA mutation 192 (109-267) days, and in all those with ovarian cancer 219 (110-273) days. In the breastcancer cohort, progression free survival in patients with BRCA mutation was 109 (95% CI 53-168) days, in those without BRCA mutation 54 (49-54) days, and in all those with breast cancer 54 (51-106) days. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common adverse events were fatigue (45 [70%] of patients with ovarian cancer, 13 [50%] of patients with breast cancer), nausea (42 [66%] and 16 [62%]), vomiting (25 [39%] and nine [35%]), and decreased appetite (23 [36%] and seven [27%]). |
| Conclusions: | Our study suggests that olaparib is a promising treatment for women with ovarian cancer and further assessment of the drug in clinical trials is needed. |