Immune-Based Treatment Helps Fight Aggressive Breast Cancer, Study Finds

Women with an aggressive type of breast cancer lived longer if they received immunotherapy plus chemotherapy, rather than chemo alone, a major study has found.

The results are expected to change the standard of care for women like those in the clinical trial, who had advanced cases of “triple-negative” breast cancer. That form of the disease often resists standard therapies, and survival rates are poor. It is twice as common in African-American women as in white women, and more likely to occur in younger women.

Researchers said the new study was a long-awaited breakthrough for immunotherapy in breast cancer. Until now, most progress had been in other cancers, including lung cancer and melanoma, an aggressive skin cancer.

These findings may lead to the first approval by the Food and Drug Administration for an immunotherapy drug to treat breast cancer. But the approval would likely be limited to a certain type of aggressive cancer.

Although triple-negative tumors occur in only about 15 percent of patients with invasive breast cancer in the United States (or nearly 40,000 each year), they account for a disproportionate share of deaths, as many as 30 percent to 40 percent.

“These women really needed a break,” Dr. Ingrid Mayer, a breast cancer specialist at Vanderbilt University, said in a telephone interview. “Nothing has worked well.”

Dr. Mayer, who was not part of the study, called the findings “very significant.” She said she had received consulting fees from seven drug companies, including Genentech, which is the maker of the immunotherapy drug in the study and paid for the research.

The term triple-negative refers to the tumors’ lack of sensitivity to the hormones estrogen and progesterone, and their lack of a protein called HER2, which is a target of treatment.

The immunotherapy in the study was atezolizumab (brand name Tecentriq), which belongs to a class of drugs called checkpoint inhibitors; the chemotherapy was nab-paclitaxel (Abraxane).

The findings were published on Saturday in The New England Journal of Medicine, and were to be presented at a meeting of the European Society for Medical Oncology, in Munich. The study included 902 patients treated at 246 medical centers in 41 countries. Genentech, which is part of Roche, has already submitted the data to the F.D.A. for approval.

Checkpoint inhibitors like atezolizumab work by helping T-cells — a type of white blood cell that is part of the immune system — recognize cancer and attack it. Research that led to these drugs won this year’s Nobel Prize in medicine.

The drugs generally work for fewer than half of patients but can bring lasting recoveries even to people who were severely ill. Side effects can be dangerous, even life-threatening, and treatment costs more than $100,000 a year.

In other cancers, researchers sometimes describe the tumors as “hot,” meaning they tend to have many mutations — genetic abnormalities that the immune system can recognize as foreign and attack.

But breast cancers tend to be relatively “cold,” with fewer mutations. The immune system is less likely to recognize them as invaders, which may help explain why previous studies of checkpoint inhibitors in breast cancer have been somewhat disappointing, researchers say.

In the new study, the key to success seems to have been giving chemotherapy along with immunotherapy.

“Chemo takes away the invisibility cloak the cancer has managed to put on,” Dr. Mayer said.

The chemo may help to ignite the immune system, in part by killing cancer cells that then spill substances the T-cells detect as foreign and begin to hunt.

The new study “is a big deal and has been the buzz of the breast cancer research world,” said Dr. Larry Norton of Memorial Sloan Kettering Cancer Center in an email. He was not involved in the study, although he said he had done paid consulting work for the past two years for the maker of Abraxane.

Beyond changing treatment practices, he said the research “opens the door to new approaches to harness the immune system to fight breast cancer, and there is every reason to expect major advances there.”

He cautioned that the combined treatment would have to be studied further, to assess side effects.

Dr. Kevin Kalinsky, a breast cancer specialist at NewYork-Presbyterian/Columbia University Irving Medical Center, suggested that patients like those in the study should talk to their doctors “about whether it is possible for them to get access to the medication while we’re waiting for F.D.A. approval.”

He did not take part in this study. He said he has received consulting fees from about 10 drug companies, including Genentech.

The women in the study had triple-negative breast cancer that had been newly diagnosed and had become metastatic, meaning it had begun to spread. Once that occurs, the outlook is grim, with many patients surviving 18 months or less.

Half received chemo alone, and half were given chemo plus immunotherapy.

Among those who received the combination, the median survival was 21.3 months, compared with 17.6 months for those who received chemo alone. The difference was not statistically significant.

But when the researchers looked at women who had a marker called PD-L1 on their cancer cells, the results were striking: The median survival was 25 months in the combination group, versus 15.5 months with just chemo. That finding has not been analyzed statistically, and the patients are still being followed.

Doctors say the survival difference is important.

“This is truly a game changer,” said Dr. Sylvia Adams, an author of the study from NYU Langone Health’s Perlmutter Cancer Center.

Cancer patients with the PD-L1 marker tend to respond better to checkpoint inhibitors than those without it. In this study, 41 percent of patients had the marker. Genentech is seeking approval for treatment in triple-negative patients with the marker.

Dr. Adams said some patients, after initial treatment with both types of drug, have been doing well for two or three years with immunotherapy alone.

The “million-dollar question,” she said, is whether they can safely stop the immunotherapy if they have no sign of cancer. For the time being, they are sticking with the treatment.

She noted that patients in the study had some of the expected side effects of immunotherapy, including lung and pancreas inflammation.

Dr. Adams said she accepted no money from drug companies, but her medical center did receive money from Genentech to pay for the research.

Maribel Ramos, 42, was being treated at another hospital, which recommended chemo for her advanced triple-negative breast cancer.

“I was very worried because I know with that type of cancer, chemo doesn’t work,” Ms. Ramos said. She has three daughters: a 23-year-old and 10-year-old twins.

Her sister, a nurse at New York University, told her about the study there, and she began treatment in February 2016. She didn’t know it at the time, but she had been picked at random to receive the combined treatment. Within a few months, her tumors began to shrink. Nine months ago, for the first time, a scan found no sign of cancer. She is staying on immunotherapy.

“I just feel so happy that you can live longer,” Ms. Ramos said. “I wish that all the ladies that are fighting cancer, especially triple-negative, could get this medicine. I would recommend that all women get a second opinion, and sometimes even a third opinion.” She added, “This can save your life.”

About 266,120 new cases of invasive breast cancer are expected in women in 2018 in the United States, and 40,920 deaths.