Research & Clinical Trials

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Research & Clinical Trials > Research Findings > Updates on PARP Inhibitor Research

Updates on PARP Inhibitor Research

PARP inhibitors are a type of medication that holds promise for treating BRCA-related cancers. These drugs block an enzyme used by cells to repair damage to their DNA. In women without BRCA mutations, PARP inhibitors may work by keeping cancer cells from repairing themselves once they’ve been damaged by chemotherapy, while sparing healthy cells. Researchers believe that PARP inhibitors may be particularly effective against cancers in people with BRCA mutations, since their tumor cells have problems repairing DNA already, and the PARP inhibitors make that worse. The medications are still being tested in clinical trials, and are not yet FDA-approved for use outside the clinical research.

Early PARP inhibitor research in advanced hereditary cancers in people with BRCA mutations has been promising. In the first trials, the drugs effectively treated some people with BRCA mutations and advanced cancers; however, not all patients benefitted — the cancers of some research participants progressed while they were taking PARP inhibitors. More work is needed to determine who may best respond to this potential new treatment.

Early PARP inhibitor study results

In 2009 encouraging results of Phase II clinical trials involving PARP inhibitors were presented at the American Society of Clinical Oncology (ASCO) conference and published in peer-reviewed journals. One study involved women with metastatic breast cancer who were treated with chemotherapy, with or without iniparib (formerly called BSI 201). The women who received iniparib with chemotherapy showed impressive results — three times as many showed improvement compared to those who received chemotherapy alone. On average, women who received iniparib had no progression of their disease for about 3.5 months longer than those on chemotherapy alone, lived about 3.5 months longer, and suffered no greater side effects.

Another Phase II clinical trial investigated olaparib, the PARP inhibitor drug formerly known as AZD2281 in women with known BRCA1 or BRCA2 mutations and metastatic breast cancer. In this study the PARP inhibitor was given with no other treatment to women whose cancer had progressed after prior chemotherapy treatments. Participants received either a low dose (100 mg twice daily) or a high dose (400 mg twice daily). The higher dose resulted in a complete response (no measurable cancer during treatment) for one woman, and 10 partial responses (the cancer was at least 50% smaller or did not increase). Overall, the response rate for the group taking the higher dose was 41%, compared to 22% in the group who took the lower dose. Most side effects were not severe and were primarily fatigue and nausea. Researchers reported that the lung metastases of one woman in the study, who continues to take the medication, have not progressed in the 18 months since she began the olaparib.

A third study investigated olaparib for advanced ovarian cancer in BRCA mutation carriers. This Phase II clinical trial studied women with known BRCA 1 or BRCA 2 mutations and recurrent ovarian cancer. In this study the PARP inhibitor was given as a “single agent” (without other treatment) to women whose cancers had progressed after several previous courses of chemotherapy. As in the breast cancer study, women in this trial were given one of two doses: a low dose (100 mg twice daily) or a high dose (400 mg twice daily). Thirty-three of the women were evaluable at 400 mg bd and 24 at 100 mg bd. The overall response rate was 33% at the higher dose and 12.5% at the lower dose. Of the women on the high dose, 58% experienced clinical benefit compared to 17% of the women on the lower dose who experienced clinical benefit. Side effects were mild and included nausea (44%), fatigue (35%), and anemia (14%). More serious side effects were rare and were primarily nausea and a low white blood cell count. Researchers concluded that olaparib is well tolerated and active in women with advanced ovarian cancer.

The results of these Phase II studies led to larger Phase III studies to determine whether PARP inhibitors extend the life of women with advanced cancers.

Recent PARP inhibitor news


Iniparib was used in a Phase III clinical trial for patients with metastatic triple negative breast cancer as part of a randomized trial. Two distinct populations were enrolled: one group of women who were newly diagnosed with metastatic disease and had not yet received any therapy received iniparib as “first line therapy.” A second group had already been treated for metastatic cancer, which had progressed prior to beginning the clinical trial. All patients received the chemotherapy agents gemcitabine and carboplatin. Half of the patients also received iniparib; the others did not. The first-line therapy group of patients showed no overall improvement in survival or progression-free survival. However, patients who received iniparib as a second- or third-line therapy did show improvement in this preliminary data.

It is too early to conclude that iniparib is ineffective against triple negative or hereditary breast cancer. Researchers are still assessing the study results to determine whether certain groups of participants did respond well to the medication. Unknown at this point is whether women who received iniparib as a second- or third-, or fourth-line treatment improved, whether some patients — those with BRCA mutations, for example — were among the people whose cancer responded best to treatment, and whether the medication might have a better effect on women with earlier stage cancers who receive the drug before their cancer has spread beyond the breast and lymph nodes. More information will likely be presented in June at ASCO’s annual meeting. Research updates were presented at our Joining FORCEs conference in several sessions, including: Focus on BRCA and triple-negative breast cancers, New treatments for hereditary ovarian cancer, and Metastatic breast cancer — what’s new?

Given the overwhelmingly positive Phase II study results, the less positive Phase III results may seem surprising . It is important to remember the difference in purpose and scope of the trials. Phase II trials involve fewer patients and aim to identify the appropriate dosage to maximize effectiveness and safety. Phase III trials are much larger and are intended to confirm or not confirm the effectiveness of a drug, as well as provide information for physician labeling.

International pharmaceutical company Sanofi-Aventis has indicated that patients who are currently enrolled in Phase II or Phase III trials for metastatic breast cancer should receive uninterrupted access to this drug, whether they are receiving it as a first-, second- or third-line treatment. Patients who are currently enrolled in the Expanded Access Protocol (EAP) can continue to get iniparib if they are second- or third-line patients. A new consent form will be required to continue. However, based on the analysis of the Phase III data, no new first-line patients will be accepted into the EAP, and the company recommends first-line study participants discontinue treatment with iniparib. If patients and their physicians think iniparib should be continued based upon the individual’s potential risk and benefit, a new consent form will be required. The enrollment process for patients who are waiting to be enrolled in the EAP program has not changed for second-, third- and fourth-line patients.

Sanofi- Aventis has not yet analysed data from the Phase III study showing which patients benefitted most from Iniparib. They will be asking particularly whether women with BRCA1 or BRCA2 mutations are more sensitive, as would be expected from a PARP inhibitor. This analysis will be important in better understanding how iniparib works.

Sanofi-Aventis is communicating with physicians who have enrolled patients in the trial, and is seeking guidance from the FDA about sharing data with patient groups. The company has also submitted an abstract for this year’s ASCO meeting to report these findings. Sanofi-Aventis plans to continue its ongoing clinical trials with iniparib for breast, lung and ovarian cancers.


Preliminary results of a phase I study using the PARP Inhibitor MK-4827 for women with ovarian cancer were recently presented at the Society of Gynecologic Oncologists annual meeting. Before enrolling in the study, all participants had been previously treated with chemotherapy and had experienced progression of their cancer. Half of these patients benefited from the PARP inhibitor. Of 39 women enrolled, 10 had partial responses and eight others had stable disease for a minimum of 12 weeks. The two groups combined had a clinical benefit rate of 46%. The primary objectives of the study were safety and tolerability to determine the ideal dose for larger, phase II studies. The most common side effects were nausea, vomiting, anorexia, fatigue, low blood counts, and constipation.

The study included two phases: the initial dose-escalation phase included many BRCA1/2 mutation carriers as participants. The second dose-expansion phase included women with sporadic platinum-resistant ovarian cancer. Of the 39 patients included in the first study phase, 15 had unknown BRCA status, five were BRCA negative, and 19 were BRCA positive. Eleven of the 19 women with BRCA-positive mutations (58%) benefited from treatment with MK-4827 — four achieved stable disease and seven had partial responses. Seven women with BRCA-unknown status (47%) had clinical benefit, but none of the small group of BRCA-negative patients had stable disease or partial responses. Several patients had progression-free survival (PFS) lasting a year or more, including one who had a partial response and associated PFS of more than 500 days, and another whose PFS fell just short of 500 days.


Despite encouraging early research on olaparib for breast cancer, AstraZeneca announced that new studies of the drug will focus primarily on women with ovarian cancer who do not carry BRCA1/2 mutations.

In September 2013, AstraZeneca initiated Phase III clinical program for olaparib, in development for patients with BRCA mutated ovarian cancer.

PARP Inhibitor Open Research Studies

There are several PARP inhibitor studies open for different populations of patients. There is some evidence that different PARP inhibitors work differently so not all may have similar results in clinical trials. If you are considering enrolling in a clinical trial, it is recommended that you discuss the study with your health care team and the research team for each study. You can view a list of PARP Inhibitor studies enrolling people with breast cancer. We will be adding links to the different studies based on cancer type, (and when applicable, cancer subtype), stage of cancer, and type of PARP inhibitor. Please check our PARP Inhibitor clinical trials page for updates.

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