For women facing ovarian cancer, there are now more options for treatment. A relatively new class of drugs called PARP inhibitors has shown promise in treating patients with specific types of ovarian cancer. Now, clinical trial results suggest that the group of patients able to benefit from these drugs may soon expand. Importantly, “benefit” is measured in numbers of months cancer can be held in check. In this case the benefit is somewhat modest, but still an important step forward in a disease without many treatment options.Read More
The study also showed that patients whose cancers have not responded after multiple rounds of chemotherapy may respond to niraparib—which is significant, because in the past, cancers that had not responded to multiple rounds of chemotherapy were largely thought to be resistant to PARP inhibitors.
How PARP Inhibitors Work—And For Whom
Poly ADP ribose polymerase (PARP) inhibitor drugs work by preventing cancer cells that have been damaged—often during the course of chemotherapy treatment—from naturally healing. To accomplish this, and, in turn, effectively kill the cancer cell, the PARP-inhibitor drug blocks the necessary mechanism of repair, the PARP enzyme, which the cancer cell requires to fix single-strand breaks in its DNA.
“The use of PARP inhibitors has really kind of exploded in ovarian cancer and it’s very exciting,” Dr. Ritu Salani, a gynecologic oncologist at Ohio State University Wexner Medical Center, told SurvivorNet in a previous conversation about who can benefit from PARP inhibitors. “There are several different PARP inhibitors that are available in the market and all of them have actually shown that there’s been enhanced benefit or survival outcomes in patients who have BRCA mutations.”
The PARP inhibitors currently approved by the U.S. Food and Drug Administration (FDA) include Olaparib (Lynparza), Niraparib (Zejula), and Rucaparib (Rubraca). PARP inhibitors do have very significant side effects, and their ability to benefit women can vary greatly.
The BRCA Question
The reason that having a BRCA gene mutation plays into whether someone can benefit from PARP inhibitors is that tumor cells with BRCA mutations have something called “homologous recombination deficiency,” which makes it difficult for the cells to repair damaged DNA. The PARP inhibitors make that process even more difficult, in turn causing cancer cells to die.
But importantly, tumors with BRCA mutations aren’t the only cancers that have homologous recombination deficiency. Up to 25 percent of ovarian cancers without BRCA mutations may also have it. It was in these patients—those with homologous recombination deficiency but without BRCA mutations—that the researchers investigated PARP inhibitor benefit.
Treatment Timing and Previous Response to Chemo: Other Factors To Consider With PARPs
“Who should get a PARP inhibitor is the fundamental question,” Dr. Michael Birrer of the University of Alabama Birmingham’s O’Neal Comprehensive Cancer Center, previously told SurvivorNet, adding that, for many women diagnosed with ovarian cancer, the “when” is an equally pressing question.
For some women, particularly those who carry BRCA gene mutations, PARP inhibitors may be used early on during treatment, perhaps directly after initial surgery or chemotherapy. For other women, the drugs might be prescribed down the line, after multiple rounds of chemotherapy, surgery, or other means of treatment.
For ovarian cancers without BRCA mutations, PARP inhibitors were previously only used after a response to chemotherapy.
But in the Lancet study, 33 percent of women who had not responded to their last dose of chemotherapy did benefit from niraparib; they responded for at least four months.
“We don’t normally see response rates of more than 10 percent in women who have had four, five and six chemotherapy treatments,” Dr. Kathleen Moore of the University of Oklahoma, the study’s lead author, told MedicalXpress.
And while four months may not seem like much, Dr. Moore added, “Those additional months are important. They are never enough, but several months of disease stabilization is better than none. They can get people to Christmas or to see a new grandchild or to another milestone. Then, if they are stabilized and feeling better, they might be able to take another drug or go on a clinical trial.”
The study was a phase II clinical trial—which means researchers will need to scale their trial to a larger population of patients as a next step.
But for now, Dr. Moore said, “This is another piece of the puzzle that helps our patients live longer […] Until we can cure patients, we are doing our best to find treatments that buy them meaningful periods of time, until we can provide them with the next effective line of therapy.”