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Abstract Background - Standard management for HR+/HER2- metastatic breast cancer (MBC) comprises concurrent aromatase inhibitor (AI) and cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), providing improved progression-free (PFS) and overall survival over anti-estrogen alone. Eventual resistance mechanisms potentially include phenotypic changes, clonal selection, and new mutations. We theorized that limited progressive disease (LPD) would be more common on combination therapy due to eventual new mutations or clonal selection, in comparison to generalized progressive disease (GPD) occurring more frequently on AI alone due to phenotypic cellular changes across all disease sites. Potentially loco-regional treatment (LRT) options could significantly extend disease control in selected patients on combined therapy. Methods - Patterns of progressive disease (PD) for 55 historical AI-only treated controls (group A) were compared to those for 60 patients on combined treatment with an AI and a CDK4/6 inhibitor (group B) for first-line management of HR+/HER2- MBC. Mode of progression was classified as general (GPD - PD in the majority of lesions) or limited (LPD - PD in up to three lesions in a single organ). All LPDs were assessed for suitability for LRT at time of progression. PFS was assessed for those with LPD who continued present treatment after locoregional therapy. Results - LPD occurred in 13 of 55 patients (23.6%) in group A compared to 26 of 60 (43%) in group B (p = 0.026). For LPD patients, all 13 cases in group A were considered appropriate for LRT but only 3 (23.1%) received it and all patients also switched systemic therapy. In group B, 23 of 26 LPD patients were considered suitable for LRT and 16 (57.7%) received it, of whom 11 then continued first line systemic treatment. For these 11 group B patients median PFS was 12+ months (range 3 to 36+ months). LRT consisted of RT in 14 cases (bone in 13 cases, lymph node in one case) and resection in one (isolated brain metastasis). Conclusion - Patients treated with combined CDK4/6i and AI for first line HR+/HER- MBC were significantly more likely to develop LPD than those on single agent anti-estrogen, where local therapy could often be delivered with no change to systemic therapy. This strategy, applied to 11 of 60 combination treated patients (18%), delivered a median PFS in excess of a year. In contrast more general PD was more commonly observed in patients treated with AI alone, warranting change in systemic therapy. Citation Format: Andrew Redfern, Ngie Law, Indunil Weerasena, Lisa Spalding, Hilary Martin. Locoregional Management Based on Mode of Progression for HR+/HER2- metastatic breast cancer Treated with Combined CDK4/6 inhibitor with Aromatase inhibitor abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-01.
Redfern et al. (Thu,) studied this question.