Unexpected win in cancer fight

New immunotherapy drugs worked when they should not have.

No one expected the four young women to live much longer. They had an extremely rare, aggressive and fatal form of ovarian cancer. There was no standard treatment.

The women, strangers to one another living in different countries, asked their doctors to try new immunotherapy drugs that had revolutionized treatment of cancer. At first, they were told the drugs were out of the question — they would not work against ovarian cancer.

Now it looks as if the doctors were wrong. The women managed to get immunotherapy, and their cancers went into remission. They returned to work; their lives returned to normalcy.

The tale has befuddled scientists, who are struggling to understand why the drugs worked when they should not have. If researchers can figure out what happened here, they may open the door to new treatments for a variety of other cancers thought not to respond to immunotherapy.

“What we are seeing here is that we have not yet learned the whole story of what it takes for tumors to be recognized by the immune system,” said Dr. Jedd Wolchok, chief of the melanoma and immunotherapeutics service at Memorial Sloan Kettering Cancer Center in New York.

“We need to study the people who have a biology that goes against the conventional generalizations.”

Four women hardly constitutes a clinical trial. Still, “it is the exceptions that give you the best insights,” said Dr. Drew Pardoll, who directs the Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins Medicine in Baltimore.

The cancer that struck the young women was hypercalcemic small cell ovarian cancer, which typically occurs in a woman’s

teens or 20s. It is so rare that most oncologists never see a single patient with it.

But Dr. Douglas Levine, director

of gynecologic oncology at New York University Langone Medical Center, specialized in this disease. A few years ago, he discovered that the cancer was driven by a single gene mutation. The finding was of little use to patients — there was no drug on the horizon that could help.

Women with this form of ovarian cancer were sharing news and tips online in a closed Yahoo group. Levine asked to become part of the group and began joining the discussions. There he discovered patients who had persuaded doctors to give them an immunotherapy drug, even though there was no reason to think it would work.

The women reported that their tumors shrank immediately.

The idea behind immunotherapy is to dismantle a molecular

PHOTOS BY DANIEL RODRIGUES/THE NEW YORK TIMES Oriana Sousa, who had a rare, aggressive form of ovarian cancer, works out in Marinha Grande, Portugal, Feb. 10. Traditional treatments failed, but with immunotherapy her tumors shrank so much that there is no evidence of disease.

Sousa said, “People who don’t know what I have been through, they can’t imagine I am an oncology patient.”