BSI-201, an Investigational Drug, plus Chemotherapy May Offer New Treatment Option for Triple-Negative Breast Cancer

A randomized Phase II study, featured during the plenary session of the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO) , shows that women with metastatic triple-negative breast cancer who received the investigational PARP inhibitor BSI-201, in combination with conventional chemotherapy, lived significantly longer and experienced significantly better progression-free survival than women who received standard chemotherapy alone.

“The results of this study provide early evidence that BSI-201, a potent inhibitor of PARP1, or poly (ADP-ribose) polymerase-1, 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,” said Joyce O’Shaughnessy, MD, co-director of the Breast Cancer Research Program at Baylor-Charles A. Sammons Cancer Center in Dallas, Texas.

Triple-negative breast cancers (TNBC) are particularly hard to treat since they lack receptors for estrogen, progesterone and HER2, which are targeted by widely available and effective drugs. African American women are 3 times more likely than white or Hispanic women to be diagnosed with triple-negative breast cancer.

In this study, clinical benefit rate (defined by complete and partial responses and stable disease of at least 6 months), response rate, progression-free survival (the time it takes for cancer to progress), and overall survival were compared among 116 women with metastatic triple-negative breast cancer who were randomly assigned to receive a standard chemotherapy treatment (gemcitabine and carboplatin) plus BSI-201, or standard treatment alone.

Approximately 62 percent of patients receiving BSI-201 showed clinical benefit, compared with 21 percent in the chemotherapy only group. The overall response rate to treatment with the drug combination containing BSI-201 was significantly greater (48 percent) than in the group receiving only standard chemotherapy (16 percent). Women who received BSI-201 had a median survival of 9.2 months and median progression-free survival of 6.9 months compared with 5.7 months and 3.3 months, respectively, in women who received standard treatment alone.

Efficacy and Safety
BiPar Sciences Inc, a California-based subsidiary of French drug maker Sanofi–Aventis involved in the development of novel cancer therapies, reported interim safety data from this trial during the annual San Antonio Breast Cancer Symposium (SABCS) in December 2008, showing that the drug was well tolerated with no added toxicities compared with chemotherapy alone.

While inhibition of PARP has demonstrated significant anti-tumor effects in several cancers, its activity does not appear to be critical for normal, non-cancerous cells. Thus, PARP inhibition has the potential to impair a fundamental mechanism of tumor growth without rendering damage to normal cells, implying a lower risk for side effects in patients who receive PARP-inhibitor-based therapies

In general, BSI-201 has shown a strong safety profile and no significant toxicities attributable to drug in studies of more than 200 patients treated to date with monotherapy, as well as in combination with chemotherapeutic regimens.

In the trial, the incidence of side effects was similar between the two groups. BSI-201 itself was well-tolerated and did not contribute any new side effects nor add to the known side effects of gemcitabine and carboplatin.

Future research
The researchers believe that BSI-201 has first-in-class and best-in-class potential as targeted therapy for several types of cancer. The trial drug is a leading candidate in the field of PARP inhibitors and is the furthest along in clinical development of this novel therapeutic approach.

Based on the results of the Phase II trial, California based BiPar Sciences Inc will be initiating a Phase III clinical trial in triple negative metastatic breast cancer in the second half of 2009. This Phase III program has been guided by preliminary safety and efficacy data from a Phase II study in the same patient population.

ASCO 2009 abstract:

• O'Shaughnessy J, Osborne C, Pippen J, Yoffe M, et al. Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple-negative breast cancer (TNBC): Results of a randomized phase II trial. J Clin Oncol 27:18s, 2009 (suppl; abstr 3).

For more information (posters):

• Preclinical Activity of BSI-201 + Chemotherapy in Triple Negative Breast Cancer, American Association for Cancer Research, April 2009
• O’Shaughnessy J, Osborne C, Blum J, Pippen J, Yoffe M, et al. Triple Negative Metastatic Breast Cancer: A Phase 2, Multi-Center, Open-Label, Randomized Trial of Gemcitabine/Carboplatin (G/C) With or Without BSI-201, a PARP Inhibitor. SABCS Poster 2120, December 2008.

Also read these Pubmed abstracts:

• Stead LA, Lash TL, Sobieraj JE, Chi DD, Westrup JL, et al. Triple-negative breast cancers are increased in black women regardless of age or body mass index. Breast Cancer Res. 2009;11(2):R18. Epub 2009 Mar 25.

Help your Patient to better understand:

• Triple Negative Breast Cancer Foundation

Photo courtesy of the American Society of Clinical Oncology.

Progress Against Breast and Gynecologic Cancers: Highlights from ASCO

Advances in the treatment of cancers that primarily affect women, including breast and gynecologic cancers, were presented in Orlando at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO), the world’s leading professional organization representing physicians who care for people with cancer.

“Studies presented during the 45th Annual Meeting of the American Society of Clinical Oncology demonstrate continued progress against breast, ovarian and cervical cancers, which are major causes of cancer mortality worldwide,” said Eric P. Winer, MD, Chair of ASCO’s Cancer Communications Committee and professor of medicine at Harvard Medical School. “One study tells us that women can safely avoid unnecessary blood tests and can delay toxic treatment for ovarian cancer recurrence without compromising their longevity. Others report on a promising new class of targeted drugs for some of the most difficult-to-treat breast cancers. And others provide more effective and less invasive options for treating cervical cancer, which is a particularly significant problem in developing countries.”

Studies highlighted during ASCO include:

• No survival advantage to treating ovarian cancer relapse based on rising CA125 levels, compared with waiting for symptoms. A study featured in ASCO’s plenary session reports that starting treatment immediately for an ovarian cancer relapse based on CA125 protein levels found in the blood does not improve overall survival, compared with delaying treatment until symptoms arise. The findings should allow women to avoid the anxiety and cost associated with frequent blood testing and the toxicity of early treatment.
• PARP inhibitors show promise for hard-to-treat breast cancers. Two studies, including one featured in ASCO’s plenary session, report promising data on a new class of targeted drugs called PARP inhibitors. Poly (ADP-ribose) Polymerase (PARP) has a well-established role in DNA repair processes, and small molecule inhibitors of PARP have been developed as chemotherapy sensitisers for the treatment of cancer. The subsequent demonstration that PARP inhibition is selective for BRCA1 or BRCA2 deficiency suggests that PARP inhibitors may be particularly useful for the treatment of cancer with BRCA mutations. The plenary study reports that women with hard-to-treat “triple-negative” breast cancer who received the PARP inhibitor BSI-201 (BiPar Sciences Inc) along with conventional chemotherapy had 60% better survival outcomes compared with chemotherapy alone than women who received chemotherapy alone. A second study reports that women with BRCA-deficient advanced breast cancer experienced tumor shrinkage after receiving the PARP inhibitor olaparib as a single agent.
• Gemcitabine plus chemoradiation improves cervical cancer survival. Adding the drug gemcitabine (Gemzar) to cisplatin-based chemotherapy and radiation therapy extends overall survival among women with locally advanced cervical cancer. This study was primarily conducted in developing countries, where cervical cancer screening programs are limited.
• Sentinel node biopsy is an effective option for early-stage cervical cancer. Most women with early-stage cervical cancer can safely undergo sentinel node biopsy – a technique in which only one or two lymph nodes are removed to determine whether cancer has spread – in lieu of the traditional, more invasive pelvic lymph node removal, which can lead to more significant side effects. Sentinel node biopsy was also as effective for detecting cancer spread to atypical areas of the pelvis.

For more information, read these PubMed abstracts

• Sivanesaratnam V. Third S. S. Ratnam Memorial Lecture 2007. Ovarian cancer: Is there hope for women? J Obstet Gynaecol Res. 2009 Jun;35(3):393-404.
• Gupta D, Lis CG, Vashi PG, Lammersfeld CA. Impact of improved nutritional status on survival in ovarian cancer. Support Care Cancer. 2009 May 31. [Epub ahead of print]
• Turgut O, Tandogan I, Yilmaz MB, Gul I, Gurlek A. CA125 levels among patients with advanced heart failure: An emerging independent predictor for survival. Int. J Cardiol. 2009 May 13. [Epub ahead of print]
• Interim phase 2 results for PARP inhibitor BSI-201 at San Antonio Breast Cancer Symposium. Cancer Biol Ther. 2009 Jan;8(1):2-3.

Help your patients understand:

• For consumer-oriented information about the studies in this article, please refer your patients to ASCO’s patient website.

New studies answer key questions about the treatment of gastrointestinal cancers

Findings from a number of large clinical trials of new treatment regimens for gastrointestinal cancers were released today at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO), being held in Orlando, May 29 - June 2, 2009 and will be highlighted in Onco’Zine – The international Cancer Blog.

“The studies presented today answer many important questions about the best care for people with gastrointestinal cancers,” said Nicholas Petrelli, MD, medical director of the Helen F. Graham Cancer Center in Wilmington, Delaware. “These large, conclusive trials tell us what works, and importantly, tell us what doesn’t work. Some settle long-time debates in the field, others demonstrate that the current standard of care is actually superior to experimental treatments, and others will allow patients to avoid unnecessary side effects or surgery.”

The results presented include:

• First-ever data on bevacizumab as adjuvant therapy finds no benefit in colon cancer: A phase III trial finds that adding the targeted therapy bevacizumab (Avastin, Roche), to standard adjuvant chemotherapy did not improve disease free survival for patients with locally advanced colon cancer.
• Surgery unnecessary for majority of patients with advanced colorectal cancer: Most patients with metastatic colorectal cancer can safely avoid surgery on their primary tumors.
• A trial compares common adjuvant treatments for pancreatic cancer: A phase III trial comparing the adjuvant treatments most commonly used for pancreatic cancer in the United States and Europe, gemcitabine (Gemzar, Eli Lilly and Company) and 5-FU/FA, respectively, found that there is no difference in survival between the two regimens, though gemcitabine was associated with fewer side effects.
• The largest study to date on anal cancer supports the current standard: A phase III study finds that the current standard of care for anal cancer should not be changed, and that ongoing maintenance therapy after initial treatment is not effective.
• Oxaliplatin does not improve outcomes for rectal cancer: Adding oxaliplatin (Eloxatin, Sanofi-Aventis) to standard treatment in patients with locally advanced rectal cancer does not improve tumor response. However, a preliminary analysis seems to suggests that the treatment may reduce distant metastases.

For more information:

• American Society of Clinical Oncology
• 2009 ASCO annual meeting abstracts

Reference:

• Medical-Oncology (at Boomja.com)