Rachakonda, S.

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.

Abstract Background: Leukemia, a type of cancer of the blood forming tissues, compromises the immune system putting the body at risk of aggressive infections like septicemia. This can not only progress to septic shock but also death. The occurrence of the two conditions makes it almost necessary to understand the epidemiological patterns to increase the rates of survival. This study assesses the trends in mortality in patients with leukemia and septicemia in the United States from 1999-2023. Methods : We analyzed death certificates of adults aged 5 to 84 years' from the CDC-WONDER database with Leukemia (ICD-10 codes: C91, C92) and Septicemia (ICD-10 codes: A40, A41) from 1999-2023. Age-adjusted mortality rates (AAMR) per 100,000 population were stratified by gender, race, census region, year and age. Join-Point analysis was performed to estimate annual percent change (APC) and average annual percent change (AAPC) in mortality trends, along with 95% confidence intervals (CIs). Results : Between 1999 and 2023, Leukemia and Septicemia caused 56,497 deaths in patients aged 5 to 84 years. The total AAMR decreased from 0.78 in 1999 to 0.66 in 2023. Demographically, AAMR among the men decreased significantly from 1.04 to 0.85 (AAPC: -0.65; 95% CI: -0.80 to -0.49). Females experienced a decline in mortality from 0.59 to 0.46(AAPC: -0.44; 95% CI: -0.71 to -0.17). In terms of race, a slight decrease in mortality was witnessed in the mortality of Non-Hispanic (NH) Black or African Americans from 0.91 to 0.7 (AAPC:-1.13 ; 95% CI: -1.43 to -0.82), moreover the AAMR in the Hispanics decreased from 0.8 to 0.63 (AAPC: -0.04; 95% CI: -0.04 to -0.58) while those among the white community decreased from 0.78 to 0.68 (AAPC: -0.39; 95% CI: -0.58 to -0.19). Moreover, the Asian community also experienced a declining death rate. Geographically, regions in the Midwest showed the highest overall AAMR (0.75), followed by the West,Northeast and areas in the South with an overall AAMR of 0.72 . Between the urban and rural areas, rural areas had a higher AAMR as compared to the urban areas with an overall AAMR of 0.17. When stratified according to states, AAMRs varied highly from the highest in Kentucky (0.89) to the lowest in Maine(0.26). Conclusion: The overall mortality rates for leukemia and septicemia decreased between the years 1999-2023. The greatest change was seen in males, regions in the Northeast, racially in NH Blacks and the rural areas.