Tripathy D, et al. - Researchers evaluated the effectiveness and safety of ribociclib plus endocrine therapy in premenopausal women with advanced, hormone receptor (HR)-positive breast cancer. Progression-free survival was seen to be increased by ribociclib plus endocrine therapy vs placebo plus endocrine therapy and this therapy was seen to have a manageable safety profile in patients with premenopausal, HR-positive, HER2-negative, advanced breast cancer. A new first-line treatment option for these patients could be represented by the combination.

Methods

• Experts conducted this phase 3, randomised, double-blind, placebo-controlled trial at 188 centres in 30 countries.
• The patients that were considered eligible were premenopausal women aged 18–59 years who had histologically or cytologically confirmed HR-positive, HER2-negative, advanced breast cancer; an Eastern Cooperative Oncology Group performance status of 0 or 1; measurable disease as per Response Evaluation Criteria in Solid Tumors version 1.1 criteria, or at least one predominantly lytic bone lesion; and had not received previous treatment with cyclin-dependent kinases 4 and 6 inhibitors.
• They permitted the endocrine therapy and chemotherapy in the adjuvant or neoadjuvant setting, as was up to one line of chemotherapy for advanced disease.
• Authors randomly assigned the patients (1:1) via interactive response technology to receive oral ribociclib (600 mg/day on a 3-weeks-on, 1-week-off schedule) or matching placebo with either oral tamoxifen (20 mg daily) or a non-steroidal aromatase inhibitor (letrozole 2·5 mg or anastrozole 1 mg, both oral, daily), all with goserelin (3·6 mg administered subcutaneously on day 1 of every 28-day cycle).
• They masked the patients and investigators to treatment assignment.
• The intention to treat efficacy analyses were performed, and safety was evaluated in all patients who received at least 1 dose of any study treatment.
• Investigator-assessed progression-free survival was the primary endpoint.

Results

• Findings suggested that between Dec 17, 2014, and Aug 1, 2016, 672 patients were randomly assigned: 335 to the ribociclib group and 337 to the placebo group.
• Results demonsteated that per investigator's assessment, median progression-free survival was 23·8 months (95% CI 19·2–not reached) in the ribociclib group vs with 13·0 months (11·0–16·4) in the placebo group (hazard ratio 0·55, 95% CI 0·44–0·69; p < 0·0001).
• Neutropenia (203 [61%] of 335 patients in the ribociclib group and 12 [4%] of 337 in the placebo group) and leucopenia (48 [14%] and four [1%]) were the grade 3 or 4 adverse events reported in more than 10% of patients in either group.
• In 60 (18%) of 335 patients in the ribociclib group and 39 (12%) of 337 in the placebo group serious adverse events occurred, of which 15 (4%) and six (2%), respectively, were attributed to the study regimen.
• Researchers noted that because of adverse events, 12 (4%) of 335 patients in the ribociclib group and ten (3%) of 337 in the placebo group discontinued treatment.
• They did not found any treatment-related deaths.
• As per data, a total of 11 deaths occurred (five [1%] in the ribociclib group and six [2%] in the placebo group) during or within 30 days after treatment, most of which were due to progression of the underlying breast cancer (three [1%] and six [2%]).
• The cause of the remaining two deaths in the ribociclib group was an intracranial haemorrhage in an anticoagulated patient, and a pre-existing wound haemorrhage in another patient.