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Abstract The addition of metastasis-directed radiotherapy (MDRT) to immunotherapy in patients with advanced urothelial carcinoma (aUC) has shown promising results. We report the real-world data from the ARON-2 study (NCT05290038) on the impact of conventional (CRT) or stereotactic body radiotherapy (SBRT) on the outcome of aUC patients receiving pembrolizumab after platinum-based-chemotherapy. Medical records of 837 patients were reviewed from 60 institutions in 20 countries. Two hundred and sixty-two patients (31%) received radiotherapy (cohort A), of whom 193 (23%) received CRT and 69 (8%) received SBRT. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. With a median follow-up of 22.7 months, the median OS was 10.2 months, 6.8 months and 16.0 months in no RT, CRT and SBRT subgroups (p = 0.005), with an 1y-OS rates of 47%, 34% and 61%, respectively (p

Background: Triple-negative breast cancer (TNBC) remains a clinically challenging subtype due to its aggressive nature and limited treatment options post-neoadjuvant failure. Historically, capecitabine has been the cornerstone of adjuvant therapy for TNBC patients not achieving a pathological complete response (pCR). However, the integration of new modalities such as immunotherapy and PARP inhibitors has prompted a re-evaluation of traditional post-neoadjuvant approaches. Methods: This review synthesizes data from pivotal clinical trials and meta-analyses to evaluate the efficacy of emerging therapies in the post-neoadjuvant setting. We focus on the role of immune checkpoint inhibitors (ICIs), PARP inhibitors (PARPis), and antibody-drug conjugates (ADCs) alongside or in place of capecitabine in TNBC treatment paradigms. Results: The addition of ICIs like pembrolizumab to neoadjuvant regimens has shown increased pCR rates and improved event-free survival, posing new questions about optimal post-neoadjuvant therapies. Similarly, PARPis have demonstrated efficacy in BRCA-mutated TNBC populations, with significant improvements in disease-free survival (DFS) and overall survival (OS). Emerging studies on ADCs further complicate the adjuvant landscape, offering potentially efficacious alternatives to capecitabine, especially in patients with residual disease after neoadjuvant therapy. Discussion: The challenge remains to integrate these new treatments into clinical practice effectively, considering factors such as drug resistance, patient-specific characteristics, and socio-economic barriers. This review discusses the implications of these therapies and suggests a future direction focused on personalized medicine approaches in TNBC. Conclusions: As the treatment landscape for TNBC evolves, the role of capecitabine is being critically examined. While it remains a viable option for certain patient groups, the introduction of ICIs, PARPis, and ADCs offers promising alternatives that could redefine adjuvant therapy standards. Ongoing and future trials will be pivotal in determining the optimal therapeutic strategies for TNBC patients with residual disease post-neoadjuvant therapy.