San Antonio

I'll be attending and have a list of seminars and posters I wish to see. Lots going on this year, and I hope to incorporate what I learn into my 145-page MBC Guide, which I keep up-to-date regarding research and treatments.

Below from my MBC Guide is a description of therapies for people with BRCA mutations. You (and others) are welcome to request a complimentary copy of the 145 page booklet by visiting the top of this page: https://community.breastcancer.org/forum/8/topics/831507?page=3#idx_73

Research and Potential Therapies Solely for Patients with BRCA1 and/or BRCA2 Mutations

Patients harboring BRCA1 or BRCA2 (BRCA1/2) gene mutations account for approximately 5% of all breast cancers and approximately 15–20% of hereditary breast cancers. The prevalence of BRCA1/2 germline mutations is considerably higher among certain ethnic groups (e.g., Ashkenazi Jews) and in certain geographic areas.According to recent estimates, 55–65% of women who inherit a BRCA1 mutation and around 45% of women who inherit a BRCA2 mutation will develop breast cancer by the age of 70, and an increasing number of specific therapies (such as PARP inhibitors described below and platinum chemotherapies) are being studied in this subset of patients.

A substance that blocks an enzyme in cells called "PARP." PARP helps repair DNA when it becomes damaged. DNA damage may be caused by many things, including exposure to UV light, radiation, certain anticancer drugs, or other substances in the environment. In cancer treatment, blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. Overall, PARP inhibitors are a type of targeted therapy increasingly being evaluated in certain groups of cancer patients.

Topics in this section include the following:

• Carboplatin vs. Docetaxel (Taxotere)
• Lurbinectedin (PM01183) (Not Yet FDA-Approved for MBC Patients)

• Olaparib (Lynparza) (Not Yet FDA-Approved for MBC Patients, but has received Priority Review status)
• Talazoparib (BMN673) (Not Yet FDA-Approved for MBC Patients)
• Veliparib with and Without Carboplatin (Combination Not Yet FDA-Approved for MBC Patients)

• Carboplatin vs Docetaxel (Taxotere): According to one study, patients with BRCA1 and/or BRCA2 mutations with any ER, PR, and HER2 status experienced significantly greater response and progression-free survival with carboplatin than with docetaxel.In one study, the median Progression Free Survival (PFS) for patients with BRCA1/2 mutations in the carboplatin group was 6.8 months versus 3.1 months for BRCA1/2 mutation-negative patients in the carboplatin group; the PFS was 4.8 months for patients with BRCA1/2 mutations in the docetaxel group vs. 4.6 months for BRCA1/2 mutation-negative docetaxel group.From: http://www.cancertherapyadvisor.com/sabcs-2014/car.../
• Lurbinectedin (PM01183) (Not Yet FDA-Approved for MBC Patients): According to one study, Lurbinectedin shows promising clinical benefit in pretreated patients with metastatic breast cancer and BRCA1 or BRCA2 mutations, including patients previously treated with platinum.Of the 54 patients with evaluable data (61% of whom had two or more metastatic sites), the Overall Response Rate (ORR) was 39% in patients receiving the fixed 7 mg/m2 dose, and 44% in patients dosed at 3.5 mg/m2, with an ORR of 40.7%. The best overall response included a complete response in one (2%) patient, partial response in 21 (39%) patients, and stable disease in 23 (43%) patients. Just 9 (17%) patients with advanced metastatic breast cancer experienced progressive disease. The median duration of response was 6.7 months and progression-free survival was 4.1+ months.Notably, platinum pre-treated patients demonstrated an ORR of 26%. From: http://www.esmo.org/Conferences/Past-Conferences/E...
• Olaparib (Lynparza) (Not Yet FDA-Approved for MBC Patients, but has received Priority Review status): Olaparib is an oral polymerase (PARP) inhibitor that has promising antitumor activity in patients with metastatic breast cancer and a germline BRCA mutation.In a randomized Phase 3 study of 302 HER2 negative mbc patients with germline BRCA mutations who had received no more than 2 prior chemotherapy regimens, olaparib was compared with a single-agent therapy of the physician's choice.Median progression-free survival was significantly longer in the olaparib group than in the standard-therapy group (7.0 months vs. 4.2 months); and the response rate was 59.9% in the olaparib group and 28.8% in the standard-therapy group. In Oct. 20917, this drugreceived Priority Review status from the FDA.Priority Review is a mechanism used by the FDA to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease.From: http://www.nejm.org/doi/full/10.1056/NEJMoa1706450

• Talazoparib (BMN673) (Not Yet FDA-Approved for MBC Patients): In terms of the potency of PARP inhibition, Talazoparib surpasses Veliparib, Olaparib (Lynparza), rucaparib (Rubraca), and niraparib (Zejula). In a small Phase 1 trial of 18 patients with germline BRCA-mutated breast cancer, the response rate was 50%.

The Phase 2 "Abrazo" study of Talazoparib included patients with advanced breast cancer harboring a BRCA1/2 mutation: Cohort 1 included 49 patients who had responded to the last platinum-containing regimen for metastatic disease and had disease progression more than 8 weeks after the last platinum dose. Cohort 2 included 35 patients with 3 or more prior non-platinum cytotoxic regimens for metastatic disease (i.e., no prior platinum treatment). One-third of the patients had triple-negative breast cancer, half had hormone receptor–positive tumors, and only a few patients had HER2-positive disease. The mean number of prior cytotoxic regimens was three. The objective response rate and was 28% across the two cohorts. Specifically, Cohort 1 patients had an objective response rate of 21% (with 4 patients being complete responders), and Cohort 2 patients had an objective response rate of 37%. Objective responses were observed in 23% of patients with BRCA1 mutations and in 33% of patients with BRCA2 mutations. Notably, 26% of patients with TNBC mbc responded, as did 29% of those with hormone receptor–positive disease (with any HER2 status). Stable disease was achieved in 36% of Talazoparib-treated patients (18% of each cohort), the clinical benefit rate was 41% overall (stable disease for at least 24 weeks), and the median duration of response was 4.9 months. From: http://www.ascopost.com/issues/july-10-2017/potent...

• Veliparib with and without Carboplatin (Combination Not Yet FDA-Approved for MBC Patients): In a dual study of mbc patients with BRCA mutations, Phase 1 patients received carboplatin and Veliparib, which is a PARP inhibitor. In a companion Phase 2 trial, patients received single-agent Veliparib, and upon progression, received the combination of carboplatin and Veliparib. In the Phase 1 trial of the carboplatin and Veliparib combination, the progression-free survival (PFS) was 8.7 months, and the overall survival (OS) was18.8 months, with three patients remaining complete response (CR) beyond 3 years.In the Phase 2 trial of Veliparib alone, the PFS was 5.2 months and the OS was 14.5 months.(Only one of 30 patients responded to the combination therapy after progression on Veliparib alone).From: https://www.ncbi.nlm.nih.gov/pubmed/28356425

Bestbird, thank you for going. Please please post your notes on what you see.

I downloaded the app to my phone (anyone can do that) so that I can get the abstracts, but I haven't started wading through. I work in the journal business -- haven't heard of anything groundbreaking. Doesn't mean there won't be good data.

That schedule has a lot of interesting topics, and I wish I was attending. What are my options for watching online, getting abstracts and papers, etc.? Can you tell me about the app, pajim? For me it doesn't have to be groundbreaking, it just has to give me clues to help with decision-making.

I really want to find the paper or whatever is available. I want to see the risk for each of the listed mutations.This could explain a lot...