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Olaparib shows promise in trials

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    Posted: Jun 05 2017 at 6:00pm
Just got this in my inbox https://medlineplus.gov/news/fullstory_166241.html

SUNDAY, June 4, 2017 (HealthDay News) -- A twice-daily pill could help some advanced breast cancer patients avoid or delay follow-up sessions of chemotherapy, a new clinical trial reports.

The drug olaparib (Lynparza) reduced the chances of cancer progression by about 42 percent in women with breast cancer linked to BRCA1 and BRCA2 gene mutations, according to the study.

Olaparib delayed cancer progression by about three months. The drug also caused tumors to shrink in three out of five patients who received the medication, the researchers reported.

"Clearly the drug was more effective than traditional chemotherapy," said Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society.

"This is a group where a response is more difficult to obtain -- a young group with a more aggressive form of cancer -- and nonetheless we saw a close to 60 percent objective response rate," he said.

The study was funded by AstraZeneca, the maker of Lynparza.

Olaparib works by cutting off the avenues that malignant cancer cells use to stay alive, said lead researcher Dr. Mark Robson. He's a medical oncologist and clinic director of Clinical Genetics Service at Memorial Sloan Kettering Cancer Center in New York City.

The drug inhibits PARP, an enzyme that helps cells repair damaged DNA, Robson said.

Normal cells denied access to PARP will turn to the BRCA genes for help, since they also support the repair of damaged DNA, Robson said.

But that "backup capability" is not available to breast cancer cells in women with BRCA gene mutations, Robson said.

"When you inhibit PARP, the cell can't rescue itself," Robson said. "In theory, you should have a very targeted approach, one specifically directed at the cancers in people who have this particular inherited predisposition."

Olaparib already has been approved by the U.S. Food and Drug Administration for use in women with BRCA-related ovarian cancer. Robson and his colleagues figured that it also should be helpful in treating women with breast cancer linked to this genetic mutation.

Edited by mainsailset - Jun 05 2017 at 6:00pm
dx 7/08 TN 14x6.5x5.5 cm tumor

3 Lymph nodes involved, Taxol/Sunitab+AC, 5/09 dbl masectomy, path 2mm tumor removed, lymphs all clear, RAD 32 finished 9/11/09. 9/28 CT clear 10/18/10 CT clear
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123Donna View Drop Down
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Jun 05 2017 at 9:41pm
This is good news for BRCA positive women.


DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Post Options Post Options   Thanks (1) Thanks(1)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Jan 08 2018 at 8:04am


OlympiAD: A Phase III trial of olaparib monotherapy versus chemotherapy for patients with HER2-negative metastatic breast cancer (mBC) and a germline BRCA mutation

DR LOVE: So anyhow, let’s talk about the OlympiAD trial. Maybe you can talk about the design of the study and what you found.

DR ROBSON: So this was a pragmatic trial, just because back when we were trying to figure out how to study PARP inhibitors in breast, we had a very, very difficult time coming up with something that would be acceptable to everybody. And certainly we couldn’t replicate the ovarian experience.

So we took essentially the EMBRACE design and took folks who had anthracycline/taxane-treated disease, HER2-negative, germline BRCA mutation and had 2 or fewer prior lines of chemotherapy, randomized 2:1 to the tablet formulation of olaparib versus physician’s choice of capecitabine, eribulin or vinorelbine, with the primary endpoint being PFS and targeting a hazard ratio of about 0.63. So we were looking for an improvement from a baseline of about 4 months. And the control arm was the predicted PFS.

And we had to get 230 events, and so we randomized 302 patients and wound up with what you saw, which is a hazard ratio of about 0.58 as a blinded independent central review.

DR LOVE: I think that one of the numbers that surprised me the most was the response rate.

DR ROBSON: Yes. Sixty percent response rate overall versus about 20% in the patients who were getting conventional chemotherapy. But I think when you look at the control arm, I don’t think any of us who treat a lot of breast cancer would be particularly surprised.

DR LOVE: No. Absolutely. No. Sixty percent — and were you expecting that?

DR ROBSON: No. That was better than we expected. I mean, remember, in the ICEBERG it was about 40% for the 400. So that was probably a slightly more heavily pretreated group of patients. But it was quite nice to see, 9% complete response rate and, importantly, no difference in response rates between the patients who had either triple-negative or hormone receptor-positive disease, which was a nice backup to the subset analyses.

DR LOVE: How about adverse events?

DR ROBSON: Largely the ones that we’ve been talking about. I mean, really the main issues were nausea/vomiting, anemia. Those were the big ones. And in chemotherapy, as you would have expected, it was neutropenia, a little bit of nausea, LFT abnormalities and hand-foot syndrome from the capecitabine, so no unanticipated toxicities. You had mentioned earlier MDS/AML, no cases of MDS/AML. And I think that the MDS/AML story hopefully is going to become not exactly moot, but I think we’re going to get more and more reassurance as more and more patients are treated.

DR LOVE: So one of the questions that this leads to of tremendous practice importance relates to mutation testing.

DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Jan 12 2018 at 3:40pm

The U.S. Food and Drug Administration today expanded the approved use of Lynparza (olaparib tablets) to include the treatment of patients with certain types of breast cancer that have spread (metastasized) and whose tumors have a specific inherited (germline) genetic mutation, making it the first drug in its class (PARP inhibitor) approved to treat breast cancer, and it is the first time any drug has been approved to treat certain patients with metastatic breast cancer who have a “BRCA” gene mutation. Patients are selected for treatment with Lynparza based on an FDA-approved genetic test, called the BRACAnalysis CDx.

“This class of drugs has been used to treat advanced, BRCA-mutated ovarian cancer and has now shown efficacy in treating certain types of BRCA-mutated breast cancer,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “This approval demonstrates the current paradigm of developing drugs that target the underlying genetic causes of a cancer, often across cancer types.”

Breast cancer is the most common form of cancer in the United States. The National Cancer Institute at the National Institutes of Health estimates approximately 252,710 women will be diagnosed with breast cancer this year, and 40,610 will die of the disease. Approximately 20-25 percent of patients with hereditary breast cancers and 5-10 percent of patients with any type of breast cancer have a BRCA mutation. BRCA genes are involved with repairing damaged DNA and normally work to prevent tumor development. However, mutations of these genes may lead to certain cancers, including breast cancers.

Lynparza is a PARP (poly ADP-ribose polymerase) inhibitor that blocks an enzyme involved in repairing damaged DNA. By blocking this enzyme, DNA inside the cancerous cells with damaged BRCA genes may be less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of tumor growth. Lynparza was first approved by the FDA in 2014 to treat certain patients with ovarian cancer and is now indicated for the treatment of patients with germline breast cancer susceptibility gene (BRCA) mutated, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer, who have been previously treated with chemotherapy. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior hormonal (endocrine) therapy or be considered inappropriate for endocrine treatment.

Today, the FDA also expanded the approval of the BRACAnalysis CDx, an approved companion diagnostic to Lynparza, to include the detection of BRCA mutations in blood samples from patients with breast cancer.

The safety and efficacy of Lynparza for the treatment of breast cancer was based on a randomized clinical trial of 302 patients with HER2-negative metastatic breast cancer with a germline BRCA mutation. The trial measured the length of time the tumors did not have significant growth after treatment (progression-free survival). The median progression-free survival for patients taking Lynparza was 7 months compared to 4.2 months for patients taking chemotherapy only.

Common side effects of Lynparza include low levels of red blood cells (anemia), low levels of certain white blood cells (neutropenia, leukopenia), nausea, fatigue, vomiting, common cold (nasopharyngitis), respiratory tract infection, influenza, diarrhea, joint pain (arthralgia/myalgia), unusual taste sensation (dysgeusia), headache, indigestion (dyspepsia), decreased appetite, constipation and inflammation and sores in the mouth (stomatitis).

Severe side effects of Lynparza include development of certain blood or bone marrow cancers (myelodysplastic syndrome/acute myeloid leukemia) and inflammation in the lungs (pneumonitis). Lynparza can cause harm to a developing fetus; women should be advised of the potential risk to the fetus and to use effective contraception. Women taking Lynparza should not breastfeed as it could cause harm to a newborn baby.

This application was granted Priority Review, under which the FDA’s goal is to take action on an application within 6 months where the agency determines that the drug, if approved, would significantly improve the safety or effectiveness of treating, diagnosing or preventing a serious condition.

Lynparza is also approved for the treatment of patients with BRCA-mutated, advanced ovarian cancer who have received three or more treatments of chemotherapy, and for the maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer whose tumors have completely or partially responded to chemotherapy.

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm592347.htm



Edited by 123Donna - Jan 12 2018 at 3:40pm
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Asovey Quote  Post ReplyReply Direct Link To This Post Posted: Jan 13 2018 at 12:31pm
This is exciting!
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