Women with an aggressive form of breast cancer lived longer when they received immunotherapy plus chemo, rather than chemo alone, a significant study has found.
The results are expected to change the standard of care for women such as those in the change clinical trial that had progressed to cases of "triple negative" breast cancer. This form of the disease often resists standard therapies, and the survival rates are poor. It is twice as common in African-American women as it is in white women, and tends to occur in younger women.
Researchers said the new study was a long-awaited breakthrough for breast cancer immunotherapy. So far, most advances have been made in other cancers, including lung cancer and melanoma, an aggressive skin cancer.
Although three-negative tumors occur in only about 15 percent of patients with invasive breast cancer in the United States (or nearly 40,000 a year), they account for a disproportionate share of deaths, as much as 30 percent to 40 percent.
"These women really needed a break," Dr. Ingrid Mayer, a breast cancer specialist at Vanderbilt University, in a telephone interview. "Nothing worked well."
Dr. Mayer, who did not participate in the study, described the results as "very significant". She said she received counseling fees from seven pharmaceutical companies, including Genentech, which makes the immunotherapeutic in the study and pays for research.
The term "triple-negative" refers to the lack of sensitivity of the tumors to the hormones estrogen and progesterone and their lack of a protein called HER2, which is the target of the treatment.
The immunotherapy in the study was atezolizumab (brand name Tecentriq), which belongs to a class of medicines 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 of Medical Oncology in Munich. The study involved 902 patients treated in 246 medical centers in 41 countries. Genentech, part of Roche, has already submitted the data to the F.D.A.
Checkpoint inhibitors such as atezolizumab work by helping T cells – a type of white blood cell that is part of the immune system – to detect and attack cancer. Research into these drugs has won this year's Nobel Prize for Medicine.
The drugs generally work in less than half of the patients, but can also bring long-term recovery to seriously ill people. Side effects can be dangerous, even life-threatening, and the treatment costs more than $ 100,000 a year.
In other cancers, researchers sometimes describe the tumors as "hot," meaning that they have many mutations – genetic abnormalities that have the immune system can recognize as alien and attack.
But breast cancer tends to be relatively "cold," with fewer mutations. The immune system recognizes them less as intruders, which may explain why previous studies with checkpoint inhibitors in breast cancer have been somewhat disappointing, researchers say.
In the new study, the key to success seems to have been chemotherapy along with immunotherapy.
"Chemo takes away the invisibility cloak the cancer has created," Dr. Mayer.
Chemo can help to ignite the immune system by killing cancerous cells, spillage substances that recognize T cells as foreign and begin to hunt.
The new study "is a big deal and was the buzz of the breast cancer research world," Dr. Larry Norton Memorial Sloan Kettering Cancer Center in an email. He was not involved in the study, although he said he had paid paid consulting work for the Abraxane maker over the last two years.
In addition to changing treatment practices, he said that research "opens the door to new approaches to the English: He cautioned that the combined treatment should be further investigated to assess side effects.
Dr. Kevin Kalinsky, a breast cancer specialist at Irving Medical Center University in New York / Presbyterian / Columbia, suggested that patients like the Study participants should discuss with their doctors whether they will be able to access the drugs while waiting for FDA approval. "
He did not participate in this study. He said he had received consulting fees from about 10 pharmaceutical companies including Genentech.
The women in the study had triple-negative breast cancer that had been newly diagnosed and metastasized, meaning that it had started to spread. Once this happens, the outlook is grim, and many patients survive 18 months or less.
Half received chemo alone and half received chemo and immunotherapy.
Among the patients receiving the combination, median survival was 21.3 months, compared to 17.6 months for those receiving 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: median survival in the combination group was only 25 months compared to 15.5 months for chemo. This finding has not been statistically analyzed and patients are still being monitored.
Doctors say the survival difference is important.
"This is really a game changer," Dr. Sylvia Adams, author of the study from the Perlmutter Cancer Center of NYU Langone Health.
Cancer patients with the PD-L1 marker tend to respond better to checkpoint inhibitors than those without. In this study, 41 percent of the patients had the marker. Genentech seeks approval for the treatment of triple negative patients with the marker
Dr. Adams said some patients had been well on immunotherapy alone for two or three years after initial treatment with both types of medication.
The "million-dollar question," she said, was whether they could safely stop immunotherapy. They have no sign of cancer. For the time being they are sticking to the treatment.
She found that patients in the study had some of the expected side effects of immunotherapy including lung and pancreas inflammation.
Dr. Adams said she did not accept money from pharmaceutical companies, but her medical center got money from Genentech to fund the research.
Maribel Ramos, 42, was treated in another hospital that recommended chemo for her advanced triple negative breast cancer
"I was very worried because I know with this type of cancer, chemo does not work," said Ms. Ramos. She has three daughters: a 23-year-old and a 10-year-old twins.
Her sister, a nurse at New York University, told her about the trial there, and she started treatment in February 2016. She did not do I know it at the time, but she had been randomly selected to undergo the combined treatment to obtain. Within months, her tumors began to shrink. Nine months ago, a scan for the first time found no signs of cancer. She remains on immunotherapy
"I just feel so happy that you can live longer," said Mrs. Ramos. "I wish that all women who fight cancer, especially triple negative, could get this medicine, I would recommend all women a second opinion and sometimes even a third opinion." She added, "This can save your life. In the United States, by 2018, approximately 266,120 new cases of invasive breast cancer are expected in women and 40,920 deaths in women.