New drug class offers hope for breast cancer

[kkmalaysia]

Lynsey Alger
Medical Tribune
 
A new class of targeted cancer therapy called poly (ADP-ribose) polymerase inhibitors – or PARP inhibitors – have shown promise in two phase II trials in difficult-to-treat breast cancer.
 
BSI-201 shows benefit in triple-negative cancer
Potent PARP-1 inhibitor BSI-201 markedly improved outcomes in a randomized trial of 116 women with metastatic, triple-negative breast cancer – cancers lacking receptors for estrogen, progesterone and HER2.
 
When added to conventional chemotherapy the new drug increased both overall survival and progression-free survival compared to chemotherapy alone.
 
BSI-201 treatment led to a 3-fold rise in clinical benefit compared to chemotherapy only (62 percent versus 21 percent, respectively, P=0.002). Clinical benefit was defined as complete and partial responses and stable disease of ?6 months.
 
Overall response rate to treatment was 48 percent with PARP inhibition compared to 16 percent without (P=0.002), while median survival was also superior for BSI-201-treated patients, at 9.2 months versus 5.7 months (P<0.0005).
 
Women also experienced longer progression-free survival with BSI-201, with a median time of 6.9 months as opposed to 3.3 months in the control group (P<0.0001). BSI-201 was well tolerated and did not show any new side effects, nor did it add to those of conventional chemotherapy.
 
Lead author of the study, Dr. Joyce O’Shaughnessy, of the Baylor Charles A. Sammons Cancer Center, Dallas, US, said the results “provide early evidence that BSI-201 is a promising treatment for women with triple-negative breast cancer, an aggressive form of the disease for which we need new, more effective therapies.”
 
A large phase III trial is slated to substantiate the results.
 
Olaparib shrinks BRCA-deficient tumors
A second PARP inhibitor, olaparib, also reported positive results in the difficult-to-treat BRCA1 or BRCA2 deficient advanced breast cancers.
 
Over one third of women with persistent breast cancer who had already been treated with several rounds of chemotherapy showed tumor shrinkage after treatment with olaparib.
 
The small, multi-center study of 54 women looked at two doses of olaparib, 100 mg and 400 mg once-daily, evaluating 27 patients in each group. While no data is yet available for the 100 mg group, women treated with the higher dose had an overall response rate of 38 percent.
 
The most common side effects were mild fatigue, nausea and vomiting, but on the whole, olaparib was well tolerated.
 
“The findings of our study provide very promising evidence that the potent PARP inhibitor olaparib may be useful for treating BRCA-deficient breast cancers,” said Dr. Andrew Tutt, lead author and director of the Breakthrough Breast Cancer Research Unit at Kings College, UK.
 
Olaparib had already shown early promise as a treatment for BRCA-deficient ovarian cancer in a phase II study, but this is the first study evaluating olaparib alone in women with BRCA-deficient breast cancer. [J Clin Oncol 2008; 26(May 20 suppl):Abs 5510]
 
PARP inhibitors impair DNA repair
Both BRCA-deficient and triple-negative breast cancers are believed to have lost the ability for specialized DNA repair. PARP enzymes, however, are charged with repairing single-stranded DNA damage and appear to be very much active in these tumors.
 
PARP inhibitors, such as BSI-201 and olaparib, therefore divest the tumor cell of an additional repair mechanism. It is hoped the development of these drugs will leave tumors more susceptible to chemotherapy treatment and also potentiate cell death.