After recent approvals, poly-adenosine diphosphate [ADP]-ribose polymerase inhibitors (PARPis) have emerged as a frontline treatment for metastatic castration-resistant prostate cancer (mCRPC). Unlike their restricted use in breast or ovarian cancers, where approval is limited to those with BRCA1/2 alterations, PARPis in mCRPC are applied across a broader spectrum of genetic aberrations. Key findings from the phase III PROPEL trial suggest that PARPis’ accessibility may broaden, even without mandatory testing. An increasing body of evidence underscores the importance of distinct alterations in homologous recombination repair (HRR) genes, revealing unique sensitivities to PARPis. Nonetheless, despite the initial effectiveness of PARPis in treating BRCA-mutated tumors, resistance to therapy is frequently encountered. This review aims to discuss patient stratification based on biomarkers and genetic signatures, offering insights into the nuances of first-line PARPis’ efficacy in the intricate landscape of mCRPC.

Malignant melanoma is among the leading forms of cancer on a global scale, accounting for 1 in 5 skin cancers. Over the past decades, the treatment of melanoma has significantly improved following the development of therapies such as MAPK molecular therapy targeted at BRAF and MEK signaling pathways. We present real-world evidence from clinical practice in Bulgaria on the treatment of malignant melanoma with dabrafenib and trametinib from 2018 to 2022. Treatment outcomes from the real-world data are compared against the pivotal clinical trials, namely COMBI-d and COMBI-v. Outcomes are compared on the basis of metrics, including overall survival, progression-free survival, and clinical benefit. Further, iterational proportional fitting is performed to control for differences in characteristics across the patient cohorts. Results show that real-world overall survival and progression-free survival outperform results from the clinical trials, particularly with respect to COMBI-d.

Third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI) osimertinib is approved as first-line treatment against non-small-cell lung cancer (NSCLC) harboring sensitizing EGFR mutations. Herein, we perform retrospective analysis of real-world data on first-line osimertinib treatment among Bulgarian patients with NSCLC, comparing treatment outcomes to FLAURA results. Patient data were obtained from electronic health records over a 4-year period. Baseline characteristics and endpoints (progression-free survival [PFS], objective response rate [ORR], and clinical benefit rate [CBR]) were compared. Iterative proportional fitting was performed to balance patient characteristics prior to survival analysis. A total of 365 patients on first-line osimertinib were included. Partial responses were more frequent in the RWE cohort (24% vs 13%), while the opposite was noted for stable disease (63% vs 80%). Complete response frequency was comparable (2% vs 1%). The ORR was higher in the real world compared to in FLAURA (26% vs 14%), whereas CBR was slightly higher in the trial (89% vs 94%). The real-world PFS was higher than reported in FLAURA (19.1 vs 18.9 months), with more favorable outcomes in the RWE cohort beyond 18 months. RWE closely aligns with FLAURA results, suggesting even greater benefit of first-line osimertinib in the real-world setting.