Two large studies of the top-selling cancer drug Avastin released Wednesday show that the drug can slow the growth of ovarian cancer when added to chemotherapy. But in a disappointment for patients, neither study found that the expensive drug extends life expectancy.
“The amount of improvement seems to be relatively modest,” said Amit Oza, an oncologist at the Princess Margaret Hospital in Toronto who led one of the studies set to be published in the New England Journal of Medicine on Thursday.
Even these modest results energized patient advocates, who point to the lack of new treatments for ovarian cancer, which causes some 15,000 annual deaths in the United States as the eighth most common cancer among women.
“While we are looking for that silver bullet, this is a gift that shouldn’t be overlooked,” said Karen Orloff Kaplan, chief executive of the Ovarian Cancer National Alliance.
Data on survival are still being collected, but the results so far are likely too disappointing for the drug’s maker, Genentech, to seek Food and Drug Administration approval of Avastin for ovarian cancer, said company spokeswoman Charlotte Arnold. However, the company did receive approval this month from European drug authorities to market Avastin for ovarian cancer treatment there.
Both studies hinted that patients with advanced ovarian cancer may benefit more than patients with earlier-stage disease.
“There are likely to be subsets of patients with very advanced ovarian cancer who will experience a survival benefit as long as they’re being treated with Avastin,” said Robert A. Burger, an oncologist at Fox Chase Cancer Center in Philadelphia who helped lead the second study published Thursday.
But sorting out patients who might benefit from those who won’t is impossible at present. “We desperately need to figure out a way to predict the folks who are going to respond to the drug versus the folks who will only get side effects of the drug,” said Otis Brawley, chief medical officer of the American Cancer Society. Studies searching for such a test are ongoing.
In a disease in which less than half of patients survive their diagnosis for five years, even the small benefit seen in the studies pushed researchers to herald the results as significant. “We have to consider it as a potential new treatment,” Oza said.
Other experts immediately pushed back on that assertion, saying the absence of a survival benefit disqualifies Avastin as a treatment except in very advanced cases.
“Our practice does not use Avastin in newly-diagnosed([ovarian cancer) patients,” said Ursula A. Matulonis, director of gynecologic oncology at the Dana-Farber Cancer Institute in Boston. “My opinion is not changing.”
The smaller of the two studies published Thursday, dubbed ICON7, followed 1,500 women in 11 countries. All received standard chemotherapy and half received Avastin for up to 10 months after chemotherapy. In the Avastin patients, the drug halted the growth of their tumors for an extra month and a half.
The second study of 1,800 women used a higher dose of Avastin added to chemotherapy. The women who continued receiving Avastin for 10 months after chemotherapy experienced an extra four months of slow to no growth in their tumors, compared with the women who received no Avastin.
But slowing the tumors did not delay death from ovarian cancer. While the larger study, conducted by the National Cancer Institute-supported Gynecologic Oncology Group, continues to collect data, the Avastin patients so far have not survived any longer than the other patients.
At the same time, two women in the ICON7 study died of complications attributed to Avastin, one from a brain hemorrhage and one from a perforated bowel. In both studies, significantly more women taking Avastin experienced hypertension — a known adverse effect of the drug.
Burger said that oncologists need to weigh these risks against the modest benefits when considering whether to prescribe Avastin.
In cancer drug research, extending life span is the gold standard the FDA wants to see.
The FDA approved Avastin in 2004 as the first in a much-heralded class of “biological” drugs designed to squelch cancer by cutting off a tumor’s blood supply. The idea worked wonderfully in lab mice but making it work in patients has proved challenging.
Kidney cancer patients benefit the most from Avastin. But in more common cancers, such as lung and colorectal cancer, “the beneficial effect really remains modest,” said Yihai Cao, a cancer biologist at the Karolinska Institute in Stockholm. “At the end of the day you spend huge amounts of money, and the question is do you buy a longer life or a better life? It’s a key question — and a very hard question.”
In November, the agency took the unusual — and controversial — step of removing a preliminary approval for Avastin for advanced breast cancer. The agency’s head, Margaret A. Hamburg, said the risks of Avastin outweighed the benefits. The ruling drew sharp criticism from patient advocates, but long-term studies had found that the drug did not increase survival times.
Genentech, which is owned by Swiss drug giant Roche, is looking to avoid a similar episode with Avastin for ovarian cancer. “Based on the current data, there is a low likelihood that we’ll ask(FDA) for approval,” said Arnold, the Genentech spokeswoman.
Because the FDA has approved Avastin for treatment of other cancers, physicians are free to use it as they see fit, and some already prescribe it for women whose ovarian cancer has recurred or returned after shrinking. Medicare pays for Avastin for recurrent ovarian cancer, as do many large insurance companies.
But in absence of specific FDA approval, it’s unlikely insurance companies will pick up the substantial tab of Avastin for initial ovarian cancer. The drug costs about $99,000 per year per patient.