Ribociclib Dose Reductions Produce Consistent Survival Outcomes in HR+/HER2- Advanced Breast Cancer


Ribociclib Dose Reductions Produce Consistent Survival Outcomes in HR+/HER2- Advanced Breast Cancer

According to findings from the phase 3 MONALEESA-2 trial, dose adjustments of ribociclib (Kisqali) compared to the normal dose resulted in identical overall survival (OS) outcomes in patients with hormone receptor-positive, HER2-negative advanced breast cancer (NCT01958021).

During the 2022 American Society of Clinical Oncology Annual Meeting, data from the study's final protocol-specified OS analysis were presented.

According to a landmark analysis, those who had at least one reduction 3 months into treatment had a median OS of 63.1 months, compared to 65.7 months for those who had no reductions during that time period (HR, 0.96; 95 per cent CI, 0.68-1.36). Furthermore, in a time-varying Cox regression analysis of OS by dosage decrease, the median OS in the modification group was 66.0 months (95 per cent CI, 57.6-75.7) and 60.6 months (95 per cent CI, 42.5-79.2), while in the conventional group it was 60.6 months (95 per cent CI, 42.5-79.2). (HR, 0.87; 95 percent CI, 0.65-1.18).

In a presentation of the findings, Lowell Hart, MD, FACP, scientific director of clinical research at Florida Cancer Specialists and Research Institute, explained, "The ribociclib starting dose is 600 mg per day." "To control treatment-related adverse events, the MONALEESA-2 [trial] protocol allowed decreases to 400 mg or 200 mg per day." [These] decreases may be necessary to assist a patient stay on medication if they have encountered AEs."

The OS results were consistent with previous findings from the MONALEESA-3 (NCT02422615) and MONALEESA-7 (NCT02278120) studies, implying that deviating from the prescribed dose of 600 mg daily on a 3 week on/1 week off cycle in combination with endocrine therapy will result in a similar OS advantage. Notably, neither the length of therapy nor the timing of dose reduction had any effect on the results.

The MONALEESA-2 trial enrolled postmenopausal women with hormone receptor–positive HER2-negative advanced breast cancer who had not previously received treatment for the disease. Participants were randomly assigned to receive either a normal regimen of ribociclib (600 mg) on a 3-week on/1-week off schedule with 2.5 mg/day of letrozole continuously or a placebo plus letrozole.

The time from the first dosage reduction or interruption to the last dose date, referred to as relative dose intensity 2 (RDI2), was also used to evaluate the results. The total mg of the dose delivered was divided into three categories: low (64.27 per cent), medium (64.27 per cent -95.86 per cent), and high (> 95.86 per cent).

Low RDI2 had a median OS of 62.6 months (95 per cent CI: 50.0-80.7), medium RDI2 had a median OS of 63.9 months (95 per cent CI: 48.8-not achieved [NR]), and high RDI2 had a median OS of 65.3 months (95 per cent CI; 50.5-NR). The hazard ratio was 0.99 when comparing low RDI2 to high RDI2 (0.59-1.42; 95 per cent CI). Between medium and high RDI2, the hazard ratio was 0.97. (95 per cent CI, 0.68-1.38).

The researchers performed landmark analyses to assess the link between dosage decreases and overall survival. The analysis attempted to address the potential for guarantee-time bias by dividing patients into two groups ("yes" or "no" in terms of dose reduction). Patients whose exposure to the chemical above the thresholds were also excluded from the trial. The "yes" and "no" options showed if a dosage reduction occurred before the milestone time.

Among the 334 evaluable patients, 125 did not require a dose decrease (37.3%), 124 required one (37.1%), 76 required two (22.9%), and 9 required three or more (37.3%). (2.7 per cent). AEs (58.1%), dosage errors (3.3%), lack of efficacy (0.3%), physician decision (3.0%), and patient/guardian decision (3.0%) were all reasons for more than three-dose reductions (3.3 percent ). For three patients, the reduction explanation was lacking (0.9 per cent ).

The median time to first dose decrease was 3 months, and baseline characteristics of individuals who needed changes and those who didn't were comparable. The median age of individuals who needed a reduction and those who did not was 62.0 years at the start. The majority of the patients had an ECOG performance level of 1 or 2. (63.6 per cent vs 56.8 per cent).

In patients who needed at least one adjustment, the median duration of ribociclib exposure was 19.1 months, compared to 10.8 months in those who did not.

The median follow-up time between randomization and data cutoff was 79.7 months, with a median follow-up time of 49.35 months between randomization and date of last contact or death (range, 1-86.7 months). By the data cutoff date, 209 of 334 patients (62.6 per cent) needed dose reductions, while 275 needed dose interruptions (82.3 per cent).

Neutropenia was the most common all-grade adverse effect (AE) among individuals who required and did not require a dose decrease, according to a safety review. It was also due to the AE that dose reductions were induced (42.1 per cent).

Hart wrapped up his talk by summarising the findings from the three MONALEESA trials that were completed.

"Taken together, the findings from MONALEESA-2, MONALEESA-3, and MONALEESA-7 imply that patients receiving ribociclib plus endocrine therapy who require dose adjustments from the recommended starting dose due to AES or other factors can do so without jeopardising overall survival," he said.

Previous Post Next Post