Real-World Safety and Effectiveness of a Bevacizumab Biosimilar (ABP 215) in Metastatic Colorectal Cancer Patients in Canada.

BACKGROUND: ABP 215 is a biosimilar to the reference product, bevacizumab, and was one of the first biosimilars approved by Health Canada for the first-line treatment of metastatic colorectal cancer (mCRC). This study aimed to address gaps in real-world evidence (RWE) including patient characteristics, treatment safety (primary objective), and effectiveness (secondary objective) for first-line ABP 215 therapy in Canadian patients with mCRC. MATERIALS AND METHODS: Retrospective data were collected in 2 waves, at least 1 year (Wave 1) or 2 years (Wave 2) after commercial availability of ABP 215 at each participating site. RESULTS: A total of 75 patients from Wave 1 and 164 patients from Wave 2 treated with a minimum of 1 cycle of ABP 215 were included. At least one safety event of interest (EOI) was recorded for 34.7% of Wave 1 and 42.7% of Wave 2 patients. The median progression free survival (PFS) for Wave 1 and 2 patients were 9.47 (95% confidence interval [CI]: 6.71, 11.90) and 21.38 (95% CI: 15.82, not estimable) months, respectively. Median overall survival was not estimable for Wave 1 and was 26.45 months for Wave 2. CONCLUSION: The safety and effectiveness of ABP 215 observed in this real-world study were comparable to clinical trial findings and to other RWE with longer PFS in the current study.

Double Duty: Complete Pathologic Response of Two Colonic Primaries with Mosaicism of a Novel MLH1 Mutation to Neoadjuvant Pembrolizumab.

We present a fascinating case of a 57-year-old male with a novel mutation in MLH1 (MLH1:c.1288G > T, p.(Glu430*)), who presented with two synchronous colonic tumours, initially deemed unresectable, and experienced a complete pathological response on neoadjuvant pembrolizumab. Extensive genetic testing revealed post-zygotic mosaicism from the novel mutation.

Health related quality of life in older or frail patients with advanced colorectal cancer treated with dose reduced capecitabine.

OBJECTIVES: Palliative chemotherapy's role is to prolong survival while minimizing treatment toxicities to preserve or improve quality of life. We have recently published a phase II trial of dose reduced capecitabine in older or frail patients with advanced colorectal cancer (aCRC). We herein provide a robust analysis of the health related quality of life (HRQoL) data from our trial. METHODS: A single arm multi-centered phase II trial of dose reduced capecitabine (1500 or 2000 mg/m2 days one-fourteen q21 days) in older or frail patients. Participants (182 patients) were asked to complete Functional Assessment of Cancer Therapy general questionnaire (FACT-G) at enrollment, after each cycle of capecitabine, and once upon completion, if possible. RESULTS: 157 patients completed a baseline questionnaire (86%), and 137 patients (75%) completed at least one subsequent questionnaire. The mean baseline score was 81.6, out of a possible 108. The mean score peaked at 92 after cycle 10. The mean change from baseline was always positive. Patients achieving the minimal clinically important difference (MCID) ranged from 30% to 45% during treatment. Higher baseline FACT-G and Physical Well-being score were independently prognostic for improved survival (p = 0.006 and p < 0.0001, respectively). Time until definitive deterioration (TUDD) was insignificantly longer in patients with a higher baseline FACT-G (p = 0.18). CONCLUSION: Baseline HRQoL scores were independently prognostic for survival, supporting their importance. Compared to full dose, reduced dose capecitabine has previously demonstrated equivalent efficacy and reduced toxicity. We have reported dose reduced capecitabine improves quality of life in older or frail patients with aCRC, further supporting its use in the management of aCRC.

Reactive oxygen species (ROS) are a key determinant of cancer's metabolic phenotype.

Cancer cells exhibit a wide range of metabolic phenotypes, ranging from strict aerobic glycolysis to increased mitochondrial respiration. The cause and utility of this metabolic variation is poorly understood. Given that cancer cells experience heavy selection within their microenvironment, survival requires metabolic adaptation to both extracellular and intracellular conditions. Herein, we suggest that reactive oxygen species (ROS) are a key determinant of cancer's metabolic phenotype. Intracellular ROS levels can be modified by an assortment of critical parameters including oxygenation, glucose availability and growth factors. ROS act as integrators of environmental information as well as downstream effectors of signaling pathways. Maintaining ROS within a narrow range allows malignant cells to enhance growth and invasion while limiting their apoptotic susceptibility. Cancer cells actively modify their metabolism to optimize intracellular ROS levels and thereby improve survival. Furthermore, we highlight distinct metabolic phenotypes in response to oxidative stress and their tumorigenic drivers.

Third-Generation Tyrosine Kinase Inhibitors Targeting Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer.

Sensitizing mutations in the epidermal growth factor receptor (EGFR) predict response to EGFR tyrosine kinase inhibitors (TKIs) and both first- and second-generation TKIs are available as first-line treatment options in patients with advanced EGFR-mutant non-small cell lung cancer. Eventual resistance develops with multiple mechanisms identifiable both upon repeat biopsy and in plasma circulating tumor DNA. The T790M gatekeeper mutation is responsible for almost 60% of cases. A number of third-generation TKIs are in clinical development, and osimertinib has been approved by the US Food and Drug Administration for the treatment of patients with EGFR T790M mutant lung cancer after failure of initial EGFR kinase therapy. Resistance mechanisms are being identified to these novel agents, and the treatment landscape of EGFR-mutant lung cancer continues to evolve. The sequence of EGFR TKIs may change in the future and combination therapies targeting resistance appear highly promising.