Conditional progression-free survival in patients with metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer treated with first-line ribociclib and endocrine therapy: real-world data from the RIBANNA study

Abstract

Background: Progression-free survival (PFS) for patients with metastatic hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer significantly improved with cyclin-dependent kinase 4/6 inhibitors as part of first-line treatment. No data is available for these patients on how the risk of progression evolves. Therefore, we analyzed conditional PFS (cPFS), which reflects patient prognosis after initial management, that is, the probability of remaining free from progression in those who have already survived without progression for a given period.

Patients and methods: We analyzed PFS and cPFS for patients free from progression after 12, 24, and 36 months (reference time points) treated with ribociclib and endocrine therapy (ET) as first-line treatment for advanced HR+, HER2- breast cancer (aBC) within the RIBANNA noninterventional study (NCT06311383). Relevant subgroups with established prognostic factors were additionally examined.

Results: Compared with the median PFS of 35 months (95% confidence interval 32.3-38.4 months) in the overall population, the median cPFS was higher for all reference points: cPFS of 40.5 months (95% confidence interval 35.0-45.5 months) for patients who were progression-free 12 months, cPFS of 53.6 months (95% confidence interval 42.7-not reached months) for 24 months reference point, whereas for the 36 months reference point, the median cPFS was not reached. After patients had reached 2-year disease control, the initial presence of liver metastases or grade 3 disease no longer qualified as poor prognostic factors; internal organ metastases (central nervous system, liver, and lungs) showed a diminishing prognostic impact over time. A short treatment-free interval remained a relevant prognostic factor.

Conclusion: For the first time, increasing cPFS was demonstrated in patients treated with ribociclib and ET. Such information is highly relevant and reassuring for patients with HR+, HER2- aBC, and could be used to aid patient counseling and treatment decision-making, including possible de-escalation strategies. It is also a starting point for identifying dynamic prognostic factors related to long-term survival.

Keywords: RIBANNA; advanced breast cancer; conditional progression-free survival; conditional survival; metastatic breast cancer; ribociclib.

Figure 1

Patient disposition in the ribociclib (RIB) + aromatase inhibitor (AI)/fulvestrant (FUL) cohort of the RIBANNA study. Apart from the RIB + AI/FUL cohort, the RIBANNA study comprised two additional cohorts (endocrine therapy monotherapy and chemotherapy), in which a total of 410 patients were enrolled^a. The safety analysis set (SAF) of the RIB + AI/FUL cohort includes all patients without protocol deviation who received one or more doses of the study medication. The full analysis set (FAS) of the RIB + AI/FUL cohort includes all patients who received one or more doses of the study medication (SAF) and for whom at least one postbaseline evaluation was recorded. ^aEnrolled patients were defined as those who signed informed consent and were formally enrolled into the study. ^bExcluded due to no application of study medication (n = 83) or protocol deviation (n = 75). ^cExcluded due to no postbaseline evaluation (n = 89) or other reason (n = 58). ^dReasons for discontinuation after first-line (1L) therapy: end of study (n = 1), lost to follow-up (n = 159), death (n = 256), withdrawal of informed consent (n = 51), physician decision (n = 52), participation in clinical study (n = 5), change in receptor status (n = 6), and other reason (n = 69). 2L, second line.

Figure 2

Conditional progression-free survival (cPFS) Kaplan–Meier curves for first-line ribociclib + aromatase inhibitor/fulvestrant therapy at baseline (0 months) and different reference time points in the full analysis set. cPFS represents the probability of remaining alive and progression free under the condition that this patient has already survived progression free from baseline to each reference time point.

Figure 3

Conditional progression-free survival (cPFS) for first-line therapy (ribociclib + aromatase inhibitor/fulvestrant) after 2 years at baseline (0 months) and conditional on having survived for 12, 24, and 36 months. Error bars are 95% confidence intervals. PFS probabilities were calculated using the Kaplan–Meier formula and conditioned on the time being event free (surviving and being free from progression) after time zero.

Figure 4

Subgroup analysis of conditional progression-free survival (cPFS) in first-line therapy [ribociclib (RIB) + aromatase inhibitor/fulvestrant (AI/FUL)] according to common prognostic factors. cPFS was estimated after 2 years at baseline and conditional on having survived for 12, 24, and 36 months. Error bars are 95% confidence intervals. PFS probabilities were calculated using the Kaplan–Meier formula and conditioned on the time being event free (surviving and being free from progression) after time zero and were stratified by (A) menopausal status (postmenopausal or pre-/perimenopausal), (B) age at baseline (<75 years or ≥75 years), (C) presence of liver metastases (with or without), (D) G3 at initial diagnosis (yes or no), (E) presence of internal organ metastases (with or without), and (F) treatment-free interval (TFI; >12 months or ≤12 months). G, grade.