A combination of two new pills may nearly double the length of survival for patients with recurrent ovarian cancer, according to preliminary clinical trial results.
The therapy combines the drugs olaparib and cediranib. It provided nearly 18 months of progression-free survival on average, as opposed to nine months' survival with olaparib treatment alone, said Dr Joyce Liu, a gynaecologic oncologist at Dana-Farber Cancer Institute in Boston.
Liu was scheduled to present the study findings at the American Society of Clinical Oncology meeting in Chicago.
Resistance to chemotherapy
The results "compare favourably to what you'd see in chemotherapy," Liu said. This raises the possibility that this drug combination "might offer a non-chemotherapy alternative for the treatment of ovarian cancer," she said. Patients could swallow pills rather than go through intravenous chemo treatment.
As many as four out of five women with aggressive ovarian cancer experience a relapse after chemotherapy, the researchers said. When the cancer returns, it is more likely to have spread to other parts of the body and to have developed resistance to chemotherapy.
Because of this, researchers have been exploring alternate treatments for ovarian cancer that can overcome resistance to chemotherapy.
Olaparib works by targeting an enzyme called PARP that repairs DNA damage in cells and, if inhibited, could cause cancer cells to die. Cediranib blocks the growth of blood vessels in a tumour, starving the cancer of the nutrition and oxygen it needs to survive.
Both drugs are awaiting US Food and Drug Administration approval, Liu said. And as with most studies presented at meetings, the findings should be considered preliminary until published in a peer-reviewed medical journal.
The US National Cancer Institute-funded trial involved 90 women with aggressive ovarian cancer that returned after chemotherapy. Participants were randomly assigned to receive treatment with olaparib alone or a combination of olaparib and cediranib. All had cancers that responded to platinum-based chemotherapy.
Significantly improved activity
Tumors shrank more dramatically during combination therapy – 80% compared to 48% for patients who only received olaparib, the researchers found.
The combination treatment delayed disease progression, with a median progression-free survival of 17.7 months, the researchers said. Past trials of standard chemotherapy for platinum-sensitive patients have demonstrated median progression-free survival times between eight and 13 months, they noted.
Five patients in the combination arm and two patients in the olaparib-alone arm had a complete remission, the findings showed.
"If you combine these two agents, we saw significantly improved activity," Liu said.
The drugs seem to be synergistic, meaning they make each other more effective when used together.
It's not clear how the drugs work in tandem, Liu said. One theory is that by depriving cancer cells of oxygen using cediranib, they are more vulnerable to DNA damage left unrepaired by olaparib. Another is that both might work to retard the growth of blood vessels to the tumour.
Using both drugs together does increase side effects, most commonly high blood pressure, fatigue and diarrhoea, the researchers said. For the most part, side effects were managed by treating the symptoms or adjusting the dosage of the drugs, Liu said.
Dr David Fishman is a gynaecologic oncologist at Mount Sinai Hospital and a professor at Mount Sinai's Icahn School of Medicine in New York City. He called the new findings "extremely exciting".
"We're entering an era where we are identifying unique pathways for cancer, and therapies that attack the unique biology of cancer will be much more effective than we've had in the past," he said.
Fishman compared the way cancer works to a cross-country road trip, where "there are many ways to drive from New York City to Portland." These targeted therapies form road blocks along some of the major routes, forcing the cancer onto little-used and less efficient side roads.
"This is a demonstration that understanding the biology of the tumour and applying a therapy that is unique to that tumour is effective," he said.