Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer.

Abstract: Objective. To evaluate the efficacy and toxicity of the CDK4/6 inhibitors Palbociclib and Ribociclib in patients with HR+HER2-negative breast cancer. Material and methods. One hundred sixty-three (n=163) patients diagnosed with luminal breast cancer (BC) who received hormone-targeted therapy were included I the retrospective study. Patients were randomized into 2 groups depending on the treatment: the first group (n=79) received hormonal therapy and ribociclib, the second (n=84) received hormonal therapy and palbociclib. The primary analysis examined the objective response rate per RECIST 1.1 in each study group and the incidence and severity of adverse events using NCI CTCAE v5.0 toxicity criteria. Results. When analyzing objective responses according to RECIST 1.1, complete responses (CR) were not observed in groups, partial responses (PR) were detected in 15% (n=11) of patients in the ribociclib group and in 15% (n=13) — in the palbociclib group (p=0.7799), stabilization (SD) — in 43% (n=34) of cases in group 1 and in 48% (n=40) of cases in group 2 (p=0.5574); progression (PD) — in 25% (n=20) versus 15% (n=13) (p=0.1194), respectively. Leukopenia was observed in 8.9% (n=7) patients in the ribociclib group and in 26.2% (n=22) patients in the palbociclib group (p=0.0088). The incidence of neutropenia in the palbociclib group was 27.4% (n=23). The use of ribociclib was associated with a more frequent development of hepatotoxicity: 17.7% (n=14) versus 3.6% (n=3) of patients receiving ribociclib and palbociclib, respectively. There was no difference between the groups in the frequency of anemia and asthenia. Conclusion. The use of CDK 4/6 inhibitors in the treatment of patients with luminal Her2-negative breast cancer is effective, but the appointment of targeted therapy is associated with the development of adverse effects, which can affect the choice of drug depending on the comorbidity and initial clinical and instrumental parameters.

Abstract: Additional file 2: Supplementary Table 1. cfDNA Samples Included in 23This Analysisa. Abbreviations: C5D1, cycle 5 day 1; cfDNA, cell-free DNA; EOT, end of treatment; max, maximum; min, minimum; pt, patient. aOne patient experienced failed quality control. bJapanese group. cJapanese and Asian non-Japanese groups. dAsian non-Japanese group. Supplementary Table 2. Correlation Between ctDNA Fraction and Percentage Tumor Change between C5D1 and EOTa,b. Abbreviations: BL, baseline; C5D1, cycle 5 day 1; ctDNA, circulating tumor DNA; EOT, end of trial; PD, progressive disease; PR, partial response; pt, patient; SD, stable disease. aDetected ctDNA was defined as ctDNA > 0. bPatients with nondetectable ctDNA at baseline: 4 had PR/SD, 4 had PR->PD, and 2 had SD->PD. Supplementary Figure 1. Spider Plots and ctDNA Fraction of Individual Patientsa With (A) Progressive Disease, (B) Partial Response, or (C) Stable Disease. Abbreviations: AA, amino acid; ctDNA, circulating tumor DNA; EOT, end of treatment; frac, fraction. aPatient number is not representative of a patient identifier.

TL;DR: Novel treatment strategies for HR+/HER2− metastatic breast cancer focus on overcoming resistance to endocrine therapy and improving long-term outcome rates through targeted therapies combined with novel oral SERDs and other targeted therapies based on genomic profiling.

TL;DR: Attrition is high in patients with advanced breast cancer in the first three therapy lines, with approximately one in three patients not starting the next therapy line.

TL;DR: Palbociclib (PD-0332991) is an oral, small-molecule inhibitor of cyclin-dependent kinases (CDKs) 4 and 6 with preclinical evidence of growth-inhibitory activity in oestrogen receptor-positive breast cancer cells and synergy with anti-oestrogens as mentioned in this paper.

TL;DR: Among patients receiving initial systemic treatment for HR-positive, HER2-negative advanced breast cancer, the duration of progression-free survival was significantly longer among those receiving ribociclib plus letrozole than among those received placebo plus let rozole, with a higher rate of myelosuppression in the ribocIClib group.

TL;DR: This study aimed to confirm the earlier findings with this extended follow-up and show the results for subgroup and biomarker analyses, and assesses endocrine therapy resistance by clinical parameters, quantitative hormone-receptor expression, and tumour PIK3CA mutational status in circulating DNA at baseline.

TL;DR: Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy, significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive, HER2-negative advanced breast cancer.