Gogula, Naga Sai Akhil Reddy

175 Background: BRAF V600E mutations occur in ~8–12% of metastatic colorectal cancer (mCRC) and are linked to poor prognosis, therapy resistance, and limited response to anti-EGFR monotherapy. While the BEACON trial established encorafenib plus cetuximab as standard, the added value of triplet regimens remains unclear. Clarifying the efficacy and toxicity of doublet vs triplet therapies is essential to optimize care in this high-risk group. Methods: Studies published across PubMed, Embase, and Google Scholar from inception till May 2025 with reported outcomes of the desired targeted therapies for BRAF V600E-mutated mCRC were screened and finally 12 studies included in this review. Data on efficacy parameters such as overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) as well as safety indicators such as adverse events (AEs), and discontinuation rates were extracted and analyzed. Results: In the ≥2nd-line setting, doublet and triplet regimens (doublet plus binimetinib) demonstrated improved outcomes compared with cetuximab plus irinotecan/FOLFIRI, with higher OS (7.2–9.2 vs 5.6 months), PFS (4.2–4.6 vs 1.5 months), DCR (65–75% vs 31%), and a comparable incidence of severe AEs (3–5% vs 4%). Panitumumab plus vemurafenib, also in the ≥2nd-line setting, reported an OS of 7.6 months, PFS of 3.2 months, and a DCR of 27%. In the 1st-line setting, the doublet regimen plus mFOLFOX6 with longer treatment duration (~50 weeks) showed improved outcomes compared with the doublet regimen plus higher-dose cetuximab, with higher OS (30.3 vs 19.5 months), PFS (12.8 vs 6.8 months), ORR (65.7% vs 45.6%), but also a higher incidence of severe AEs (46% vs 30%). Similarly, the cetuximab + vemurafenib + irinotecan regimen outperformed conventional chemotherapy (mFOLFOX6, FOLFOXIRI, or CAPOX) ± bevacizumab, with improved OS (25.3 vs 10–15 months), PFS (11.9 vs 7.5 months), ORR (63.2% vs 37–40%), DCR (94.7% vs 75%), and a lower rate of grade ≥3 AEs (34.2% vs 65%). Conclusions: The survival benefit observed with the doublet regimen was comparable to that of the triplet, but with lower rates of adverse events and treatment discontinuation, supporting current evidence that the doublet remains the preferred option for patients with BRAF V600E–mutated mCRC who have received one or more prior lines of therapy. Although adding conventional agents such as mFOLFOX6 to the doublet in the first-line setting improved OS, PFS, ORR, and DCR, this approach was associated with higher toxicity and discontinuation rates, raising questions about its overall benefit. Emerging data on vemurafenib in combination with cetuximab and conventional agents show promise, but further studies directly comparing encorafenib- versus vemurafenib-based regimens are warranted to optimize outcomes in this patient population.

Background/Objectives: Menopause, marked by permanent cessation of menstruation, is a universal transition associated with vasomotor, genitourinary, psychological, and metabolic changes. These conditions significantly affect health-related quality of life (HRQoL) and increase the risk of chronic diseases. Despite their impact, timely diagnosis and individualized management are often limited by delayed care, fragmented health systems, and cultural barriers. Methods: This review summarizes current applications of artificial intelligence (AI) in postmenopausal health, focusing on risk prediction, early detection, and personalized treatment. Evidence was compiled from studies using biomarkers, imaging, wearable sensors, electronic health records, natural language processing, and digital health platforms. Results: AI enhances disease prediction and diagnosis, including improved accuracy in breast cancer and osteoporosis screening through imaging analysis, and cardiovascular risk stratification via machine learning models. Wearable devices and natural language processing enable real-time monitoring of underreported symptoms such as hot flushes and mood disorders. Digital technologies further support individualized interventions, including lifestyle modification and optimized medication regimens. By improving access to telemedicine and reducing bias, AI also has the potential to narrow healthcare disparities. Conclusions: AI can transform postmenopausal care from reactive to proactive, offering personalized strategies that improve outcomes and quality of life. However, challenges remain, including algorithmic bias, data privacy, and clinical implementation. Ethical frameworks and interdisciplinary collaboration among clinicians, data scientists, and policymakers are essential for safe and equitable adoption.