by Charles Bankhead
An immunotherapy-chemotherapy combination led to improvement in progression-free survival (PFS) and overall survival (OS) as initial treatment for metastatic triple-negative breast cancer (TNBC), a randomized trial showed.
In the intention-to-treat population (ITT), atezolizumab (Tecentriq) and nab-paclitaxel (Abraxane) improved PFS modestly from 5.5 months with nab-paclitaxel alone to 7.2 months with the combination (P=0.002). Median OS improved by almost 4 months with the combination, from 17.6 to 21.3 months (P=0.08). In the subgroup of patients with PD-L1-positive tumors, the combination led to further improvement in PFS (7.5 vs 5.0 months, P<0.001), and median OS was almost 10 months longer in the patients who received atezolizumab (25.0 vs 15.5 months; HR 0.62, 95% CI 0.45-0.86), as reported at the European Society for Medical Oncology (ESMO) congress in Munich.
"These results will change the way triple-negative breast cancer is treated," said Peter Schmid, MD, of St. Bartholomew's Breast Cancer Center in London. "Atezolizumab in combination with nab-paclitaxel is the first targeted treatment to improve survival in metastatic triple-negative breast cancer. It is also the first immune therapy to improve outcome in this cancer."
The findings came from the IMpassion130 trial, which involved 902 patients with untreated TNBC, 369 of whom had PD-L1-positive tumors. The patients were randomized to receive nab-paclitaxel alone or with atezolizumab. The trial had two primary endpoints: investigator-assessed PFS and OS in both the ITT and PD-L1-positive patient populations. The results provided the basis for FDA approval of atezolizumab as the first immune checkpoint inhibitor to receive a breast cancer indication.
The study was among several recent developments that have the potential to influence clinical decisions about breast cancer.
Big PFS Increase with PI3K Inhibitor
Patients with PIK3CA-mutated breast cancer lived almost twice as long without disease progression when treated with the PI3K inhibitor alpelisib plus the hormonal agent fulvestrant (Faslodex) instead of fulvestrant alone, according to another report at ESMO.
The median PFS was 5.7 months with fulvestrant alone, increasing to 11.0 months with the combination. The data showed that only patients with PIK3CA mutations benefited from the combination, providing strong support for a precision-medicine approach to treating breast cancer.
"Alpelisib is the first drug to show a benefit in a genomic subgroup of breast cancer patients," said Fabrice Andre, MD, of Gustav Roussy Institute in Villejuif, France. "This study opens the door for clinical genomics for breast cancer as the first study to show that treatment based on a patient's tumor genomic profile -- specifically, PI3KCA mutation -- can improve the outcome. These results will have a major impact for practice, because we have to implement genomic testing for breast cancer."
The trial involved 572 patients with hormone receptor-positive, HER2-negative advanced breast cancer. The study population included 341 patients with PIK3CA-mutated breast cancer. As hypothesized by investigators, alpelisib had "no clinically relevant effect ... in patients with PIK3CA non-mutant tumors," said Andre.
Reducing Anthracycline Cardiotoxicity Threat
Administration of an antihypertensive agent during breast cancer therapy significantly reduced the incidence of anthracycline-associated cardiotoxicity but did not alter the adverse heart effects of trastuzumab (Herceptin), according to a study reported at the San Antonio Breast Cancer Symposium.
The trial did not meet the primary endpoint of reducing cardiotoxicity in patients with HER2-positive breast cancer treated with trastuzumab. A prespecified secondary analysis showed that patients treated with an anthracycline, in addition to trastuzumab, had about a 50% reduction in the incidence of cardiotoxicity if they received an angiotensin-converting enzyme (ACE) inhibitor or a beta blocker during treatment, said Pamela Munster, MD, of the University of California San Francisco. Cardiotoxicity was defined as a 10% absolute decrease in left ventricular ejection fraction (LVEF) or a 5% absolute decrease if LVEF fell below 50%.
During the discussion that followed the presentation, Steven Vogl, MD, of Bronx, New York, pointed out that patients with high-risk HER2-positive tumors (bulky disease, positive lymph nodes) may receive longer courses of trastuzumab. In that setting, the cardiovascular drugs might afford patients some protection against cardiotoxicity.
The trial involved 468 patients, randomized to placebo, the ACE inhibitor lisinopril, or the beta blocker carvedilol, beginning the first day of trastuzumab treatment and continuing for 1 year. The primary endpoint was the incidence of cardiotoxicity in all patients.
Omitting Chemo from HER2-Positive Regimens
A randomized trial that evaluated the feasibility of omitting chemotherapy for HER2-positive breast cancer yielded mixed results, showing more rapid disease progression without chemotherapy but no difference in overall survival (OS).
Patients who received dual anti-HER2 therapy with trastuzumab (Herceptin) and pertuzumab (Perjeta) plus chemotherapy had a median progression-free survival (PFS) of 23.3 months, almost three times greater than the median PFS of 8.4 months with anti-HER2 therapy alone. Nonetheless, 2-year OS was virtually identical between treatment groups: 77% with chemotherapy and 76% without, Jens Huober, MD, of University Hospital Ulm in Germany, reported at the European Breast Cancer Congress in Berlin.
The trial did not include genomic testing, which could have distinguished patients with a greater likelihood of benefiting from chemotherapy from those with a lower likelihood. Huober said investigators have begun analyzing tumors with a PAM50 assay to determine whether certain patients could skip chemotherapy.
Survival Boost with Dual Hormonal Therapy for Metastatic Disease
Patients with metastatic, hormone-sensitive breast cancer lived almost 8 months longer if they received fulvestrant along with the aromatase inhibitor anastrozole (Arimidex) as compared with the aromatase inhibitor alone, long-term follow-up from a randomized trial showed.
After a median follow-up of 7 years, median OS was 49.8 months with the combination and 42.0 months with anastrozole alone (P=0.03). The 5-year survival also favored the combination (42% vs 33%), despite the fact that almost half the patients in the control arm crossed over to the combination arm, as reported in the New England Journal of Medicine.
In 2011, after a median follow-up of 3 years, an initial report from the randomized SWOG S0266 trial showed a modest improvement in PFS with the combination and a trend toward better OS, said Rita S. Mehta, MD, of the University of California Irvine.
"Some physicians changed their practice back then -- some were not convinced," Mehta told MedPage Today. "But now they should be convinced, because now we have one of the longest follow-ups and one of the largest studies."
Bone Drug Slows HR+ Breast Cancer
The addition of the bone-targeted agent denosumab (Xgeva) to an aromatase inhibitor significantly delayed disease recurrence in postmenopausal women with hormone receptor-positive breast cancer, according to study results published in The Lancet Oncology.
Patients randomized to denosumab had an 8-year disease-free survival (DFS) of 80.6% versus 77.5% for patients who received the aromatase inhibitor alone. After a median follow-up of 73 months, the denosumab group had an 18% reduction in the hazard ratio as compared with the control group (95% CI 0.69-0.98).
The positive findings added to those of a previous report on the primary endpoint of the Austrian Breast Cancer Study Group (ABCSG)-18 trial: time to first clinical fracture. The data showed a 50% reduction in the risk of fracture among women randomized to denosumab.
Results of the ABCSG-18 trial will be "practice changing," Marc Lippman, MD, of Georgetown University in Washington, said in an editorial that accompanied the Austrian authors' report.
"This study of denosumab, in addition to many randomized controlled trials of bisphosphonates, indicates that adjuvant dosing with these therapies is generally safe, leads to a substantial reduction in skeletal events and an improvement in disease-free survival, and should be part of almost all adjuvant regimens for postmenopausal hormone receptor-positive breast cancer," Lippman concluded.
Fonte: Medpage / Tradução Google
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