Great News for Triple Negative Breast Cancer

snowyday

Not sure if anyone has seen this article yet but it is good news for TN and also Her2 breast cancer.

PARP Inhibitors Target Triple-Negative, BRCA-Deficient Breast Cancers Elsevier Global Medical News. 2009 Jun 1, JS MacNeilORLANDO (EGMN) - Two drugs from a new class of agents that interfere with DNA repair showed significant activity against hard-to-treat breast cancers in separate phase II trials presented May 31 at the annual meeting of the American Society of Clinical Oncology.The novel drugs - BSI-201 and olaparib - inhibit an enzyme known as PARP (poly [ADP-ribose] polymerase). Both drug-development programs behind these agents aim to promote the death of cancer cells by thwarting the cells' ability to repair DNA damage when attacked. The two trials focused on specific breast cancers for which good therapies are lacking: BSI-201 focused on triple-negative disease that has no overly active estrogen receptors, progesterone receptors, or HER2 (human epidermal growth factor receptor 2) gene to target, and olaparib focused on breast cancers lacking BRCA1 and/or BRCA2 function. The agents have not been ruled out as possible therapies for other forms of breast cancer, however. They are being studied in other malignancies as well."When you go home, be excited. Be really excited about this. Tell your patients there is reason to be hopeful," Dr. Eric P. Winer, a professor of medicine at Harvard Medical School, Boston, told attendees in an unusually optimistic commentary for drugs early in development. Dr. Winer was not involved in either study. BSI-201 Dr. Joyce O'Shaughnessy reported that BSI-201 prolonged median survival and increased response rates in a randomized study conducted among 116 women with metastatic triple-negative breast cancer. The study, selected for a plenary presentation, added intravenous BSI-201 to a standard chemotherapy regimen of gemcitabine and carboplatin in a group of 57 patients, and compared their outcomes to those in a group of 59 women treated with only the standard regimen. Clinical benefit (the study's main end point) nearly tripled with the combination. Nearly two-thirds (62%) of women treated with BSI-201 plus chemotherapy achieved this composite measure of complete response, partial responses, and stable disease lasting at least 6 months, according to Dr. O'Shaughnessy of the breast cancer research program at Baylor-Sammons Cancer Center in Dallas. Only 16% of women who were given standard therapy alone had a clinical benefit (P for the difference = .0002), she said. The overall response rate also was significantly higher (48% vs. 16%; P = .002), as were median survival (9.2 months vs. 5.7 months; hazard ratio, .348; P = .0005) and median progression-free survival (6.9 months vs. 3.3 months; HR, .342; P less than .0001).The magnitude of benefit may actually be greater, Dr. O'Shaughnessy acknowledged, as 40% of patients in the control arm were allowed to cross over to BSI-201 after their disease progressed. The drug did not add to the toxicity associated with the chemotherapy, she added. Neutropenia was seen in about half of patients in both arms.Triple-negative breast cancer accounts for about 15% of breast cancers worldwide, Dr. O'Shaughnessy said. About 30% of patients eventually develop metastases, and most will die within a year if current therapies are used. This form of the disease is associated with dysfunction of the BRCA genes and other DNA repair defects. By inhibiting PARP, BSI-201 is believed to take away the cells' last stand against the damage deliberately caused by chemotherapy.Sanofi-Aventis of Paris and its subsidiary, BiPar Sciences Inc. of Brisbane, Calif., have announced that they are starting a phase III trial in metastatic triple-negative breast cancer beginning this summer. BiPar developed BSI-201.Olaparib Astra-Zeneca sponsored the international single-agent study of olaparib, an oral PARP inhibitor, in 54 heavily pretreated patients with advanced BRCA-deficient breast cancer. One group of 27 patients received olaparib continuously at the maximum tolerated dose of 400 mg twice a day in 28-day cycles. This was lowered to 100 mg twice a day, previously identified as a PARP inhibitory dose, in a second cohort of 27 patients.Dr. Andrew Tutt reported better outcomes with the higher dose. In all, 11 patients (41%) had a complete response, and 10 had partial responses. Six patients (22%) had partial responses at the lower dose. Median time to progression was 5.7 months at the higher dose.Olaparib was well tolerated, according to Dr. Tutt, director of the Breakthrough Cancer Research Unit at Kings College London. The most common grade 3 toxicities at 400 mg were fatigue (four patients), nausea (five), and vomiting (three).The BRCA genes have the function of DNA repair. When they don't work, PARP becomes extremely important to cell survival, Dr. Tutt said, explaining the strategy behind the trial. He compared the knocking out of PARP to sawing off the second leg of a table that already had had one leg removed. Just as the table collapses, the cell dies of what he termed "a synthetic lethal effect."Asked about the prospect for regulatory approval, Dr. Tutt told attendees that the investigators, AstraZeneca, and regulators are in "very active discussion" to advance the approval process "as fast as we possibly can."Dr. O'Shaughnessy and Dr. Tutt said they had no financial relationships to disclose. Both trials were company sponsored and included company employees as investigators. 

Shirlann

It is so good of you to post this encouraging info!

Thank you, Shirlann

bar62

This is good news...I just found this group...I think...but I posted that everywhere this morning,,,hope I wasn't too annoying...

pegc

Hi -  Since the news of my recurrent breast cancer less than a month ago my diagnosis went from a Stage 3 to Stage 4.  I am still in the process of accepting that I now have a chronic condition.  I went for a second opinion today and the Doctor talked about the PARP trial.  I would love to hear any feedback from those already in a trial.  My main concern with any of the chemo drugs is the neuropathy that I still have from my first round of treatment 3 years ago.  We just have to keep the faith and think of those less fortunate then us.