Update in Antiepidermal Growth Factor Receptor Therapy in the Management of Metastatic Colorectal Cancer

The approval of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies in the treatment of metastatic colorectal cancer (CRC) has expanded the armamentarium against this disease. This paper will review the historical progress and recent clinical developments of anti-EGFR therapies in the treatment of metastatic CRC. Novel strategies of targeting the EGFR pathway to improve efficacy as well as ongoing research in identifying specific molecular predictors of response will be discussed

Professional learning in mathematical reasoning: reflections of a primary teacher

Reasoning is an important aspect in the understanding and learning of mathematics. This paper reports on a case study presenting one Australian primary teacher’s reflections regarding the role played by a professional learning program in her developing understanding of mathematical reasoning. Examination of the transcripts of two interviews identified changes in her perceptions of mathematical reasoning by mapping interview responses against the Mathematical Reasoning Framework (Herbert et al., 2015). This change indicates that a well planned program of professional learning based on a demsonstration is efficacious in developing teachers’ understanding of mathematical reasoning

Adjunctive PD-1 Inhibitor Versus Standard Chemotherapy in Recurrent or Metastatic Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis

Objective: To investigate whether Adjunctive PD-1 inhibitors have improved clinical outcomes compared to chemotherapy alone in platinum-pretreated and platinum-naive recurrent or metastatic nasopharyngeal carcinoma (R/M NPCA). Methods: The study involved a literature search from PubMed, Cochrane CENTRAL, and Google Scholar for randomized clinical trials (RCTs) on the use of PD-1 inhibitors versus chemotherapy alone in patients with R/M NPCA. Bias was assessed using Cochrane collaboration\u27s risk of bias tool. Overall Survival (OS) was examined as the primary endpoint. Secondary endpoints were Progression-Free Survival (PFS), Objective Response Rate, Disease Control Rate (DCR), Duration of Response, and Serious/Grade ⩾3 Adverse Events. Outcomes were measured with either Mean Difference, Risk ratio (RR), or Hazard ratios (HRs) at 95% confidence interval. Results: Four RCTs were included in the meta-analysis and systematic review. OS for the monotherapy subgroup was a HR of 0.87 [0.67, 1.13] (p = 0.30) while the combination subgroup had 0.64 [0.45, 0.90] (p = 0.01). The monotherapy subgroup exhibited significantly worse outcomes in PFS (HR 1.31 [1.01, 1.68]) (p = 0.04) and DCR (RR 1.52 [1.12, 2.05]) (p = 0.007) but no significant difference in other outcomes. For combination therapy, a statistically significant benefit can be seen in all outcomes except DCR (RR 0.62 [0.38, 1.01]) (p = 0.06) which was a non-significant benefit favoring PD-1 inhibitors. Conclusion: Combination PD-1 inhibitor + chemotherapy followed by maintenance PD-1 inhibitor therapy is superior to chemotherapy alone in the first-line treatment of R/M NPCA, implying a potential benefit with the use of PD-1 inhibitors + chemotherapy with maintenance PD-1 inhibitors as first-line in R/M NPCA compared to standard chemotherapy alone

ceritinib plus nivolumab in patients with advanced alk rearranged non small cell lung cancer results of an open label multicenter phase 1b study

Abstract Introduction Induction of programmed death ligand 1 (PD-L1) expression due to constitutive oncogenic signaling has been reported in NSCLC models harboring echinoderm microtubule associated protein like 4 gene (EML4)–ALK receptor tyrosine kinase gene (ALK) rearrangements. We assessed the safety and activity of ceritinib plus nivolumab in these patients. Methods In this open-label, phase 1B, multicenter, dose escalation and expansion study, previously treated (with ALK receptor tyrosine kinase [ALK] inhibitor [ALKI]/chemotherapy) or treatment-naive patients with stage IIIB or IV ALK-rearranged NSCLC received nivolumab, 3 mg/kg intravenously every 2 weeks, plus ceritinib, 450 mg/300 mg daily, with a low-fat meal. Results In total, 36 patients were treated (a 450-mg cohort [n=14] and a 300-mg cohort [n=22]). In the 450-mg cohort, four patients experienced dose-limiting toxicities. In the 300-mg cohort, two patients experienced dose-limiting toxicities. Among ALKI-naive patients, the overall response rate (ORR) was 83% (95% confidence interval [CI]: 35.9–99.6) in the 450-mg cohort and 60% (95% CI: 26.2–87.8) in the 300-mg cohort. Among ALKI-pretreated patients, the ORR was 50% (95% CI: 15.7–84.3) in the 450-mg cohort and 25% (95% CI: 5.5–57.2) in the 300-mg cohort. The ORR point estimate was observed to be greater in patients who were positive for PD-L1 than in those who were negative for PD-L1, with overlapping CIs (e.g., at a cutoff ≥1% PD-L1, 64% of patients [95% CI: 35.1–87.2] had confirmed responses as compared with those with negative PD-L1 staining (31% [95% CI: 11.0–58.7]). The most frequently reported grade 3 or 4 adverse events were increased alanine aminotransferase level (25%), increased gamma-glutamyl transferase level (22%), increased amylase level (14%), increased lipase level (11%), and maculopapular rash (11%). The incidence of all-grade rash (grouped term) was 64% in both cohorts; grade 3 rash was reported in 29% and 14% of patients in the 450-mg and 300-mg cohorts, respectively; no grade 4 rash was reported. Conclusion Ceritinib plus nivolumab has activity; ORR appears to correlate with PD-L1 at baseline. Toxicity, especially rash, is more common than with either single agent

Novel agents in the frontline management of multiple myeloma

Significant advances in our understanding of the biology of multiple myeloma have led to exciting new opportunities in treatment. The management of this disease is rapidly changing with a plethora of clinical trials initiated with novel agents, namely thalidomide, lenalidomide and bortezomib, either alone or in conjunction with established modalities such as conventional cytotoxic agents and stem-cell transplantation. The combination of these novel agents together with conventional regimens have led to higher response rates and survival, providing options for patients whose disease is otherwise resistant to conventional therapy. These pivotal trials that lead to the approval of these three novel agents in treatment naive patients. The potential implications in the frontline treatment paradigm of multiple myeloma are discussed