Phase III Trial Fails to Find Benefit of PARP Inhibitor for Triple-Negative Breast Cancer

In a Phase III clinical trial, the addition of the PARP inhibitor iniparib to chemotherapy did not improve outcomes among women with metastatic triple-negative breast cancer. These results—which differ from those of a prior Phase II clinical trial—were presented at the 2011 annual meeting of the American Society of Clinical Oncology.??

Breast cancers that are estrogen receptor-negative, progesterone receptor-negative, and HER2-negative are called triple-negative breast cancers. Triple-negative breast cancers tend to be more aggressive than other breast cancers and have fewer treatment options.??

Iniparib belongs to a class of drugs called PARP inhibitors. The PARP enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. Drugs that inhibit this enzyme may contribute to cancer cell death and increased sensitivity to chemotherapy. Because many triple-negative breast cancers are thought to have defects in DNA repair, researchers have hypothesized that triple-negative breast cancers may be particularly vulnerable to PARP inhibition.???

A Phase II clinical trial provided hope that iniparib would indeed provide a valuable new treatment option for triple-negative breast cancer. Results published in the New England Journal of Medicine early in 2011 suggested that the addition of iniparib to chemotherapy with GemzarR (gemcitabine) and carboplatin delayed cancer progression and improved overall survival.?[1] Median overall survival was 7.7 months among women treated with chemotherapy alone and 12.3 months among women treated with chemotherapy plus iniparib.?

?A subsequent Phase III clinical trial, however, did not find a benefit. The study enrolled a larger group of women (519 versus 123 in the Phase II trial), and once again compared chemotherapy alone with chemotherapy plus iniparib for the treatment of metastatic triple-negative breast cancer. According to results presented at the 2011 annual meeting of the American Society of Clinical Oncology, the addition of iniparib did not significantly improve overall or progression-free survival.?[2] ?

Although the Phase III results were a great disappointment, it remains possible that iniparib could still provide a benefit to women whose cancer has progressed (worsened) on other treatments. Researchers are continuing to explore whether there are particular subsets of women who respond well to this treatment.?

References:?

[1] O’Shaughnessy J, Osborne C, Pippen JE et al. Iniparib plus chemotherapy in metastatic triple-negative breast cancer. New England Journal of Medicine. 2011;364:205-214.?

[2] O’Shaughnessy J, Schwartzberg LS, Danso MA et al. A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triple-negative breast cancer (TNBC). Presented at the 2011 annual meeting of the American Society of Clinical Oncology. Chicago, IL. June 3-7, 2011. Abstract 1007.?

View the original article here

Ovarian Suppression During Chemotherapy Fails to Improve Post-Treatment Menstrual Function

Among young women undergoing chemotherapy for breast cancer, use of the drug triptorelin to suppress ovarian function during treatment does not appear to improve post-treatment menstrual function. These results were published in the Journal of Clinical Oncology.???

Fertility preservation is increasingly being recognized as an important issue for young people with cancer. In premenopausal women, many chemotherapy drugs are toxic to the egg cells (oocytes) in the ovaries. If the number of remaining oocytes in the ovaries reaches a critically low point during treatment, women experience “acute ovarian failure.” This means that the ovaries stop functioning during or shortly after cancer treatment. If oocytes are lost during treatment but do not reach this critically low point, women are at risk for early menopause but may still be able to get pregnant for some time after treatment.????

Freezing embryos prior to cancer treatment is one of the most well established approaches to fertility preservation in young women, but is not always an option. One of the alternative approaches being evaluated involves the use of drugs known as gonadotropin-releasing hormone (GnRH) agonists to suppress ovarian function during chemotherapy. The hope is that this will protect the ovaries and improve post-treatment ovarian function.????

To explore the effects of the GnRH agonist triptorelin during chemotherapy for breast cancer, researchers conducted a study among premenopausal women age 44 or younger. Study participants were assigned to receive either triptorelin or a placebo. The study was originally designed to enroll 124 women, but it was stopped after only 49 women were enrolled because preliminary results indicated no benefit from triptorelin.????

Menstruation resumed in 88 percent of women in the triptorelin group and 90 percent of women in the placebo group.?Menstrual cycles resumed after a median of 5.8 months in the triptorelin group and 5.0 months in the placebo group.?

These results suggest that triptorelin does not improve post-treatment menstrual function in young breast cancer patients. Other, ongoing studies will provide more information on this topic.? ?

Premenopausal women who are interested in preserving their fertility during cancer treatment are advised to discuss their options with their physician before treatment begins.?????

Reference: Munster PN, Moore AP, Ismail-Khan R et al. Randomized trial using gonadotropin-releasing hormone agonist triptorelin for the preservation of ovarian function during (neo)adjuvant chemotherapy for breast cancer. Journal of Clinical Oncology. Early online publication January 9, 2012.?

Posted January 13, 2012?

View the original article here