First-Line Palbociclib/Letrozole Versus Ribociclib/Letrozole in Postmenopausal HR-Positive/HER2-Negative Metastatic...

Background and Objectives: Palbociclib and ribociclib are widely used with letrozole as first-line treatment for postmenopausal patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. Pivotal trials have reported different overall survival signals, but they were not designed as direct comparisons. This study evaluated real-world survival outcomes with these regimens and explored the prognostic performance of a composite clinical-inflammatory risk score. Materials and Methods: This retrospective single-center cohort included 140 postmenopausal patients treated with first-line palbociclib/letrozole or ribociclib/letrozole. Overall survival, progression-free survival, best documented response, baseline characteristics, metastatic pattern, and baseline pan-immune-inflammation value were evaluated. The composite risk score assigned one point each for progesterone receptor expression <20%, visceral metastasis, and pan-immune-inflammation value ≥477.8. Pan-immune-inflammation value was additionally evaluated as a continuous variable. The prognostic performance of the score was assessed using Harrell's c-index, bootstrap internal validation, and comparison with a parsimonious clinical model. Results: Among 140 patients, 67 received palbociclib/letrozole and 73 received ribociclib/letrozole. Median follow-up was 52.3 months. A total of 93 deaths and 118 progression-free survival events occurred. Median overall survival was 36 months with palbociclib/letrozole and 29 months with ribociclib/letrozole, with no statistically significant difference between groups (HR, 1.23; 95% CI, 0.82-1.86; p = 0.322). Median progression-free survival was 15.4 and 16.4 months, respectively (HR, 1.05; 95% CI, 0.73-1.52; p = 0.778). Median overall survival was 34 months for CRS 0-1 and 30 months for CRS 2-3 (univariable HR, 1.68; 95% CI, 1.11-2.54; p = 0.014). The apparent and optimism-corrected c-indices of the score were 0.573 and 0.570, respectively. Addition of the score to the parsimonious clinical model did not significantly improve model fit (likelihood-ratio p = 0.143). Conclusions: No statistically detectable difference in overall survival or progression-free survival between the treatment groups was observed in this cohort. Although grouped CRS was associated with overall survival in univariable analysis, the score showed limited discrimination and no statistically significant incremental prognostic value. These findings remain exploratory and require external validation.