| General information |
| Database: | DB00511 |
| Objective: | Olaparib (AZD2281), a PARP1/2 inhibitor, has been extensively investigated in clinical trials. however, limited clinical data are available about its longterm safety and antitumour activity. |
| Authors: | van der Noll R, et al |
| Title: | Longterm safety and antitumour activity of olaparib monotherapy after combination with carboplatin and paclitaxel in patients with advanced breast, ovarian or fallopian tube cancer. |
| Journal: | Br J Cancer. |
| Year: | 2015 |
| PMID: | 26180927 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | olaparib
|
| Target: | Poly [ADPribose] polymerase1
|
| Cancer Type: | breast cancer, ovarian cancer or fallopian tube cancer |
| Cancer Subtype: | advanced breast, ovarian or fallopian tube cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | olaparib monotherapy after combination with carboplatin and paclitaxel |
| Study Type: | phase I study |
| Key Patients Feature: | Eligibility criteria included the following:inability to continue olaparib in combination with carboplatinand/or paclitaxel due to persistent myelosuppression (neutro andor thrombocytopenia CTC grade X2), development of specificchemotherapyrelated adverse events, such as sensory neurotoxicity or allergic reactions or patient request to stop combinationtreatment; age X18 years; ECOG performance status p2 andadequate bone marrow, hepatic and renal function (as evidencedby thrombocytes X100 109 l 1; absolute neutrophil countX1.5 109 l 1; haemoglobin X6.2 mmol l 1; total bilirubinp1.25 upper normal limit (ULN); serum aspartate aminotransferase and alanine aminotransferase p2.5 ULN and serumcreatinine p1.5 ULN). |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Olaparib was administered in a capsuleformulation to patients at the optimal recommended monotherapy dose of 400 mg BID - previously determined in the phase Imonotherapy study - regardless of the dose level in which they had been included in the combinationphase I trial. One treatment cycle lasted 28 days. |
| Primary End Point: | longterm safety and antitumouractivity of olaparib monotherapy after combination treatmentwith chemotherapy |
| Secondary End Point: | NA |
| Patients Number: | 21 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Best overall responses demonstrated nine (43%) CR, four (22%) PR, six (29%) SD, one (5%) progressive disease (PD) and one (5%) NE. |
| Disease Control Rate: | 0.94 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | TRAEs were mostly haematological and most prominent shortly after switching from combination to monotherapy, probably due to carryover effects of chemotherapy. Over time, both severity and frequency of TRAEs decreased. |
| Conclusions: | Continued longterm daily olaparib was found to be safe and tolerable. Encouragingly, patients who showed a favourable response on earlier combination therapy maintained this response on olaparib monotherapy. |