Ribociclib Improves Overall Survival in Hormone Receptor–Positive Breast Cancer
The cyclin-dependent kinase 4/6 inhibitor ribociclib (Kisqali, Novartis) improves overall survival (OS) in women with hormone receptor (HR)–positive, human epidermal growth factor 2 (HER2)–negative breast cancer, according to interim results from the phase 3 MONALEESA-7 study (Abstract LBA1008). Previous studies had found that the addition of ribociclib to endocrine therapy improves progression-free survival (PFS) in these patients.
For the study, which was led by Dr Sara Hurvitz, 672 premenopausal women with HR-positive, HER2-negative advanced breast cancer were randomly assigned to either ribociclib or placebo, along with goserelin and standard endocrine therapy with an aromatase inhibitor or tamoxifen.
After a median follow-up of 35 months, OS was significantly longer in the ribociclib group than the placebo group, at not reached vs 41 months, respectively (hazard ratio [HR], 0.712; 95% CI, 0.54-0.95; P=.00973). The estimated OS rates with ribociclib vs placebo at 42 months were 70% vs 46%, respectively. The improvement in OS with ribociclib persisted in a subgroup analysis of patients who received an aromatase inhibitor instead of tamoxifen.
This interim follow-up did not reveal any new concerns regarding toxicity of treatment with ribociclib.
Margetuximab Improves PFS in Metastatic HER2-Positive Breast Cancer
Margetuximab improves PFS compared with trastuzumab in women with HER2-positive metastatic breast cancer who previously received at least 2 anti-HER2 regimens, according to results from the phase 3, open-label SOPHIA trial (Abstract 1000). Margetuximab is an investigational monoclonal antibody against HER2.
Researchers led by Dr Hope Rugo randomly assigned 536 women with HER2-positive metastatic breast cancer who had received at least 2 anti-HER2 regimens, including pertuzumab, to chemotherapy in combination with either margetuximab or trastuzumab.
The median PFS was 5.8 months in the margetuximab arm vs 4.9 months in the trastuzumab arm, representing a 24% reduction in disease progression (P=.03). The clinical benefit rate also was higher with margetuximab vs trastuzumab, at 37% vs 25% (P=.003). Although a trend toward a higher objective response rate occurred with margetuximab vs trastuzumab, at 22% vs 16%, it was not statistically significant (P=.06). An early analysis of OS did not find a statistically significant benefit from margetuximab.
SOPHIA found that margetuximab was significantly more likely to benefit women who were low-affinity CD16A-158F carriers, pointing to the potential use of CD16A genotyping to predict response to anti-HER2 treatments.
The safety profiles of margetuximab and trastuzumab were similar, and the increased rate of infusion-related reaction with margetuximab was managed with pre-medication.
A second interim analysis of OS is expected in late 2019.
Neratinib Improves PFS in Metastatic HER2-Positive Breast Cancer
Neratinib (Nerlynx, Puma) improves PFS compared with lapatinib (Tykerb, Novartis) in women with metastatic HER2-positive breast cancer who have received at least 2 prior HER2-directed regimens, according to a new study. Neratinib is a pan-HER tyrosine kinase inhibitor.
For the phase 3, open-label NALA study (Abstract 1002), which had Dr Cristina Saura as the first author and was presented by Dr Adam Brufsky, 621 women with stage IV HER2-positive metastatic breast cancer who had received at least 2 prior HER2-directed regimens for metastatic breast cancer were randomly assigned to receive capecitabine in combination with either neratinib or lapatinib.
The investigators reported that at up to 36 months of follow-up, centrally assessed PFS was significantly longer with neratinib than with lapatinib (HR, 0.76; 95% CI, 0.63-0.93; P=.006). PFS also was significantly longer with neratinib than with lapatinib in the restricted means analysis, at 8.8 vs 6.6 months (P=.0003). The duration of response was significantly longer with neratinib than with lapatinib (HR, 0.50; P=.0004), but the difference in OS at up to 48 months of follow-up did not reach statistical significance.
The researchers also found that fewer patients in the neratinib group required intervention for symptomatic central nervous system (CNS) metastases, which suggested a delay in CNS progression with neratinib. Although the rates of treatment-emergent adverse events were similar between the arms, the rate of grade 3 diarrhea was higher with neratinib than with lapatinib (24.4% vs 12.5%). No new safety signals were seen with neratinib.