Treatment with a cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor, such as abemaciclib, plus (+) endocrine therapy (ET) has been shown to improve survival in patients with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer, compared to ET alone. Previous research suggested that low neutrophil-to-lymphocyte ratio (NLR) and high absolute lymphocyte count (ALC) prior to treatment initiation was linked to improved survival outcomes in HR+, HER2– breast cancer. In this study, Tokunaga et al1 conducted a post hoc analysis of data from the MONARCH 2 trial to determine the prognostic significance of NLR and ALC in patients with HR+, HER2– advanced or metastatic breast cancer treated with abemaciclib.
The international, randomized, double-blind, Phase III MONARCH 2 clinical trial included patients with HR+, HER2– advanced or metastatic breast cancer who progressed during neoadjuvant or adjuvant ET, within 12 months of adjuvant ET, or during first-line ET. Patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1, had nonmeasurable bone-only disease or measurable disease, and had not received prior chemotherapy. Patients were randomized to receive either daily oral abemaciclib 150mg or placebo in combination with fulvestrant 500mg.
There were 446 patients in the abemacilib+fulvestrant group and 223 in the placebo+fulvestrant group, with 426 and 219 patients, respectively, having baseline NLR and ALC data. The abemaciclib and placebo arms had a median baseline NLR of 2.5 and 2.4, respectively, and both groups had a median baseline ALC of 1.4×109/L. In the abemaciclib arm, 49.5 percent of patients had low NLR (<2.5) and 57.5 percent had low ALC (<1.5×109/L); 50.5 and 42.5 percent had high NLR (≥2.5) and ALC (≥1.5×109/L), respectively. In the placebo group, 54.3 and 52.5 percent of patients had low NLR and ALC, respectively, while 45.7 and 47.5 percent had high NLR and ALC, respectively.
Among patients treated with abemaciclib+fulvestrant, those with low NLR had a median progression-free survival (PFS) of 21.5 months and those with high NLR had a median PFS of 14.6 months. Median overall survival (OS) was 62.6 months in the low NLR subgroup, compared to 36.5 months in the high NLR subgroup. In the placebo group, median PFS and OS were 11.2 and 43.8 months, respectively, in patients with low NLR, compared to 7.1 and 33.8 months, respectively, among those with high NLR.
Patients with high baseline ALC experienced longer PFS and OS, compared to those with low ALC. Median PFS was 17.6 and 11.6 months among patients with high ALC in the abemaciclib and placebo arms, respectively; comparatively, those with low ALC had a median PFS of 16.4 and 7.4 months in the abemaciclib and placebo arms, respectively. Among patients treated with abemaciclib, median OS was 56.4 months in the high ALC subgroup, compared to 39.0 months in the low ALC subgroup. In the placebo arm, median OS was 42.5 months among patients with high ALC, compared to 34.4 months among those with low ALC. Abemaciclib had a consistent treatment effect across NLR and ALC subgroups.
Univariate analyses showed that both baseline NLR and ALC were prognostic factors for PFS and OS. Multivariate analyses were adjusted for ECOG PS, tumor grade, presence of liver metastasis, and bone-only disease (PFS model) or sensitivity to ET, age, ECOG PS, presence of liver metastasis, and bone-only disease (OS model). According to multivariate analyses, baseline NLR showed a significant association with PFS and OS. Baseline ALC was not significantly associated with either outcome. Additional factors associated with improved PFS and OS included ECOG PS of 0, absence of liver metastases, and bone-only disease.
Further analyses showed median PFS and OS were lower in pre- and postmenopausal patients with high baseline NLR, compared to those with low baseline NLR.
In the abemaciclib arm, the objective response rate (ORR) was 55.9 percent for those with low NLR and 46.6 percent for those with high NLR. In the placebo arm, ORR was 23.6 and 16.7 percent in patients with low and high NLR, respectively. Complete response as best overall response occurred more frequently in patients with low NLR, compared to those with high NLR, in both treatment arms (abemaciclib arm: 11.8% vs. 3.4%; placebo arm: 2.2% vs. 0%). The progressive disease rate was decreased among patients with low NLR (abemaciclib arm: 9.9%; placebo arm: 20.2%), compared to those with high NLR (abemaciclib arm: 11.0%; placebo arm: 26.4%).
Grade 3 or greater neutropenia was more common in patients with low baseline NLR, compared to those with high baseline NLR. In the abemaciclib arm, Grade 3 or greater fatigue was reported more often in the high NLR subgroup, compared to the low NLR subgroup. A greater proportion of patients with low baseline ALC experienced Grade 3 or greater neutropenia, compared to those with high baseline ALC; similar trends were noted with leukopenia and lymphopenia events.
The findings of this study showed that baseline NLR was a prognostic factor for PFS and OS in patients with HR+, HER2– advanced or metastatic breast cancer receiving abemaciclib treatment.
Reference
- Tokunaga E, Miyoshi Y, Dozono K, et al. Association of neutrophil-to-lymphocyte ratio and absolute lymphocyte count with clinical outcomes in advanced breast cancer in the MONARCH 2 trial. Oncologist. 2024;29(3):e319–e329.