The immunotherapy drug Keytruda (pembrolizumab) can benefit some patients with triple negative breast cancer when given with chemotherapy before surgery and as part of the treatment regimen following surgery, according to a study presented December 12 at the San Antonio Breast Cancer Symposium (SABCS).
The study involves one of the most exciting cancer advances of the past decade — immunotherapy — applied to one of the worst types of breast cancer. Triple negative breast cancer is an aggressive subtype of breast cancer that accounts for about 10 to 20 percent of all breast cancer cases. It has proved resistant to many standard forms of treatment.
Immunotherapy drugs, such as Keytruda, have only recently been tested on breast cancer. The drugs have proved successful in lung cancer, melanoma, and a few other forms of the disease.
Typically, early-stage triple negative breast cancer is treated with chemotherapy. According to the study authors, chemotherapy is about 40 to 50 percent effective in producing a complete response to treatment, meaning there is no evidence of disease afterward.
But other options are needed to improve the numbers of patients who achieve a complete response to first-line treatment.
The study, dubbed the KEYNOTE-522 trial, involved 1,174 patients with previously untreated, nonmetastatic, triple negative breast cancer. Patients were randomized to receive Keytruda plus chemotherapy or a placebo plus chemotherapy prior to surgery. All the patients underwent surgery and received radiation therapy as needed. Patients also received either Keytruda or placebo following surgery.
Previously reported data from KEYNOTE-522 showed that patients receiving Keytruda plus chemotherapy had higher rates of complete response compared with those receiving chemotherapy alone — 64.8 percent compared with 51.2 percent after a median of 15.5 months of follow-up.
The latest data from the trial show that among patients with cancer that has spread to the lymph nodes, 64.8 percent of those receiving Keytruda plus chemotherapy had a complete response compared with 44.1 percent of those receiving chemotherapy only.
“It’s a meaningful difference in pathological complete response rates,” says the lead author, Peter Schmid, MD, PhD, a professor of cancer medicine at Barts Cancer Institute in London. “There's a benefit to adding immunotherapy to chemotherapy" in all subgroups, especially in patients with lymph-node involvement.
Typically, cancer in the lymph nodes is associated with a higher risk for recurrence. But, he says, “Patients with higher-risk disease had a different benefit with the addition of pembrolizumab to chemotherapy."
The study showed no new concerns regarding the side effects linked to Keytruda.
“Adverse event rates were consistent with the known profiles of each regimen and present no new safety concerns,” Dr. Schmid says, adding that longer-term safety data are needed.
In Other News From the SABCS…
The Breast-Cancer-Preventing Effects of Ibrance Last After Treatment Is Over
The aromatase inhibitor Ibrance (anastrozole) reduces the risk of cancer relapse years after stopping treatment, according to a study presented at the SABCS December 12. The IBIS-II Prevention trial enrolled 3,864 post-menopausal women at increased risk of developing breast cancer, such as those with a strong family history of the disease.
Seven years of follow-up, reported in 2013, showed that, compared with a placebo, the drug significantly reduced the risk of breast cancer. The new data reflects a median of 10.9 years of follow-up, and shows a significant preventive effect even 5.9 years after stopping Ibrance. Women taking the drug were 50 percent less likely to have developed breast cancer after 10.8 years compared with women who took a placebo.
“Five years of treatment carries benefits right on out to 12 years,” says the lead author Jack Cuzick, PhD, the co-chairman of the International Breast Cancer Intervention Studies. "Anastrozole reduces breast cancer risk by 49 percent in a 12-year follow-up, with a 36 percent reduction seen for the post-treatment period.”
The protective effect was larger than that seen with the drug tamoxifen (Soltamox, Nolvadex), which is also used as a preventive.
The results suggest that Ibrance should be the preferred therapy for breast cancer prevention in high-risk post-menopausal women, Dr. Cuzick says. Women who experience side effects from Ibrance should take tamoxifen instead, says Cuzick.
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Chemotherapy and Combination Therapy Are Similar in Efficacy for Luminal B Breast Cancer
Combining the drugs Kisqali (ribociclib) and Femara (letrozole) resulted in response rates similar to chemotherapy in patients with high-risk luminal B breast cancer, according to a study presented December 11 at the SABCS. The study, simultaneously published in The Lancet Oncology, evaluated endocrine (hormone) therapy combinations before surgery as an alternative to chemotherapy, which has many side effects.
The study enrolled 106 patients who received Kisqali, a category of drug known as a CDK4/6 inhibitor, combined with the aromatase inhibitor Femara, or multi-agent chemotherapy before surgery. The study showed the two treatment approaches produced similar benefits, says the lead author, Joaquín Gavilá, MD, a medical oncologist at the Instituto Valenciano de Oncologia in Valencia, Spain. The combination is less toxic than chemotherapy, says Dr. Gavilá.
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Adding Tecentriq to Chemo Regimens Doesn’t Benefit Women With Triple Negative Breast Cancer
The addition of the immunotherapy drug Tecentriq (atezolizumab) to chemotherapy prior to surgery does not appear to benefit patients with triple negative breast cancer compared with chemotherapy alone. The study, from researchers in Italy, examined whether adding the drug could boost patients' response to treatment.
The study involved 280 patients with early, high-risk, locally advanced or inflammatory triple negative breast cancer. They were randomly assigned to receive chemotherapy alone or chemotherapy with Tecentriq. The study showed that the response rate — meaning the tumor shrank or disappeared — was 43.5 percent for the group receiving chemotherapy plus Tecentriq and 40.8 percent for those receiving chemotherapy alone.
The difference is not statistically significant.
It is not clear why Tecentriq plus chemotherapy failed to show a benefit, while a similar immunotherapy checkpoint inhibitor, Keytruda, plus chemotherapy produced a beneficial response in the KEYNOTE-522 trial, also reported at SABCS.
Experts said the divergent study results could be due to numerous differences in the designs of the two studies. Moreover, additional analysis is needed to look at the potential benefit of Tecentriq over a longer period of time, says the lead author of the study, Luca Gianni, MD, the president of the Fondazione Michelangelo in Milan, Italy.