Ovarian malignant tumor is one of the most common malignant tumors in female genital organs, and the incidence is ranked the third only after cervical cancer and uterine body cancer. The US FDA approved the new anticancer drug, Ola Pani olaparib (Lynparza), as an advanced ovarian cancer patient who received chemotherapy for at least 3 times before or after single drug therapy, or suspected of advanced ovarian cancer with BRCA mutation. At the recent ASCO2017 conference, orasnico has been reported to delay the progress of BRCA related metastatic breast cancer.
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Drug name: Olaparib
Commodity name: Lynparza
Chinese Name: Ola Pani
Manufacturer: AstraZeneca (AstraZeneca)
Character: capsule
Specification: 50mg
Olaparib Ola Pani (Lynparza) drug introduction:
Olaparib Ola Pani (Lynparza) is a polyphosphate adenosine ribose polymerase (PARP) inhibitor, which blocks enzymes involved in the repair of damaged DNA. The drug is suitable for highly pretreated ovarian cancer associated with BRCA gene defects.
The effect of Ola Pani (Lynparza) was tested in a study of 137 gBRCAm related ovarian cancer subjects who were treated with the drug. The aim of the study was to detect the ratio of objective remission rate (ORR), that is, the proportion of subjects who experienced a partial reduction or complete disappearance of the tumor. The results showed that 34% of the subjects experienced an average of 7.9 months of ORR.
Research shows that, PARP Ola Pani (olaparib, OLAP) inhibitor and anti angiogenesis drugs cediranib (cediranib, CED) can be used for the treatment of recurrent ovarian cancer, and the two drugs have a synergistic effect and well tolerated. Compared with the single drug Ola Pani, Ola Pani combined cediranib can improve progression free survival in patients with platinum sensitive ovarian cancer and objective remission rate.
Comments of the researchers
New York memorial to Sloan &middot, Caitlin E. cancer center's Mark E. Robson report, a phase III clinical study (OlympiAD) from 300 breast cancer patients showed that PARP inhibitors could be used as a new drug for breast cancer patients. Compared with standard chemotherapy, the oral targeting drug Ola Pani Mike of BRCA related advanced breast cancer patients reduced the risk of progress by 42% and delayed the progress of 3 months. (summary number LBA4)
This is the first study to demonstrate the improvement of the outcome of PARP inhibitors in contrast to standard treatment in breast cancer associated with BRCA mutation. In particular, it is better to see Ola Pani in three negative breast cancer (TNBC) with BRCA mutation in the embryo.
About 3% of breast cancer patients have BRCA1 and BRCA2 mutations that reduce the cell's ability to repair the damage to DNA. Ola Pani could block other DNA repair pathways in the cells, PARP1 and PARP2. Because of the potential defects of DNA repair ability, BRCA mutant cancer cells are very sensitive to targeted PARP therapy. Ola Pani has been approved by FDA for the treatment of ovarian cancer associated with BRCA.
This study provides a very important evidence that breast cancer, which is defective in a specific DNA repair pathway, is very sensitive to targeted therapy for repair defects.
A brief introduction to the research
The study was carried out in a group of patients with BRCA mutation, hormone receptor positive or three negative metastatic breast cancer. There is no group of HER2 positive breast cancer patients, because there is a very effective targeting therapy for them.
Two lines of chemotherapy were received at most of all metastatic patients, and HR+ patients received hormone therapy. The researchers randomly assigned 302 patients to Ola Pani's tablets or standard chemotherapy (capecitabine / Changchun riebin or edrin) according to the ratio of 2 to 1, until the patient progressed or had serious adverse reactions.
Main discovery
Approximately 60% of patients with tumor size, Orapa group, and only 29% in the chemotherapy group. At a median follow-up of 14 months, Ola Pani could reduce the risk of disease progression by 42% compared with chemotherapy. The median to disease progression was 7 months and 4.2 months, respectively, in the orange group and the chemotherapy group.
After the disease progressed, the researchers continued to follow up to observe the time of the two deterioration of the tumor. The second time in the Ola Pani group was longer than the chemotherapy group, indicating that there was no rapid progress in the tumor after the stop Ola Pani treatment. At present, the total survival data of the patients are not mature enough to determine whether Ola Pani's benefits can be converted to survival benefit.
The most common adverse reactions of Ola Pani were nausea and anemia, while the most common adverse reactions in chemotherapy group were leukocyte reduction, anemia, fatigue and rash on hands and feet. The incidence of severe adverse events in the Ola Pani group was lower than that in the chemotherapy group, 37% and 50%, respectively. Only 5% of the patients stopped taking drugs because of Ola Pani's adverse reactions. The quality of life of the patients in the Ola Pani group was significantly higher.
Robson believes that Ola Pani's early treatment for metastatic breast cancer will be the best. Because Ola Pani can maintain the quality of life of patients, delay patients receiving intravenous chemotherapy time, avoid chemotherapy induced hair loss and leukocyte reduction and other adverse reactions.
Enlightenment to the next step of research
Because of the small sample size of the study, it is not possible to determine which patients can benefit most from Ola Pani treatment. PARP inhibitors are currently used in the treatment of breast cancer with 4 phase III clinical studies, which are the results of the first report. More studies are needed to determine the efficacy of Ola Pani in platinum based chemotherapy resistant patients, and whether platinum based chemotherapy is effective in patients with Ola Pani's resistance.
Chairman ASCO comments
Daniel F. Hayes, the president of the ASCO, said the expected study showed that the new treatment model would improve the prognosis of patients with BRCA positive breast cancer. It is worth mentioning that at the present time, we can not only target therapy based on gene mutation of breast cancer, but also target therapy according to the driving factors of breast cancer.
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