Commercially available physical activity monitors provide clinicians an opportunity to obtain oncology patient health measures to an unprecedented degree. These devices can provide objective and quantifiable measures of physical activity, which are not subject to errors or bias of self-reporting or shorter duration of formal testing. Prior work on so-called quantified-self data was based on older-generation, research-grade accelerometers, which laid the foundation for consumer-based physical activity monitoring devices to be validated as a feasible and reliable tool in patients with cancer. Physical activity monitors are being used in chronic conditions including chronic obstructive pulmonary disease, congestive heart failure, diabetes mellitus, and obesity. Differing demographics, compounded with higher symptom and treatment burdens in patients with cancer, imply that additional work is needed to understand the unique strengths and weaknesses of physical activity monitors in this population. Oncology programs can systematically implement these tools into their workflows in an adaptable and iterative manner. Translating large amounts of data collected from an individual physical activity monitoring device into clinically relevant information requires sophisticated data compilation and reduction. In this article, we summarize the characteristics of older- and newer-generation physical activity monitors, review the validation of physical activity monitors with respect to health-related quality-of-life assessments, and describe the current role of these devices for the practicing oncologist. We also highlight the challenges and next steps needed for physical activity monitors to provide relevant information that can change the current state of oncology practice.
Purpose: EGFR exon 19 deletion (Ex19Del) mutations account for approximately 60% of lung cancer-associated EGFR mutations and include a heterogeneous group of mutations. Although they are associated with benefit from tyrosine kinase inhibitors (TKI), the relative inhibitor sensitivity of individual Ex19Del mutations is unknown.Experimental Design: We studied the TKI sensitivity and structural features of common Ex19Del mutations and the consequences for patient outcomes on TKI treatment.Results: We found that the L747-A750>P mutation, which represents about 4% of all Ex19Del mutations, displays unique inhibitor selectivity. L747-A750>P differs from other Ex19Del mutations in not being suppressed completely by erlotinib or osimertinib, yet is completely inhibited by low doses of afatinib. The HCC4006 cell line (with the L747-A750>P mutation) exhibited increased sensitivity to afatinib over erlotinib and osimertinib, and computational modeling suggests explanations for this sensitivity pattern. Clinically, patients with EGFR L747-A750>P mutant tumors showed inferior outcomes when treated with erlotinib than patients with E746-A750 mutant tumors.Conclusions: These results highlight important differences between specific Ex19Del mutations that may be relevant for optimizing TKI choice for patients.
PURPOSE Immune checkpoint inhibitors (ICIs) are standard therapy in metastatic renal cell carcinoma (RCC). The safety and activity of the combination of ipilimumab and nivolumab in patients who have received prior ICI targeting the programmed death 1 (PD-1) pathway remains unknown. We evaluated ipilimumab and nivolumab in patients with metastatic RCC after prior treatment with anti–PD-1 pathway–targeted therapy. PATIENTS AND METHODS Patients with metastatic RCC who received prior anti–PD-1 pathway-targeted therapy and subsequently received ipilimumab and nivolumab were reviewed. Objective response rate and progression-free survival per investigator assessment were recorded. Toxicity of ipilimumab and nivolumab was also assessed. RESULTS Forty-five patients with metastatic RCC were included. All patients (100%) received prior ICIs targeting the PD-1 pathway. The median age was 62 years (range, 21-82 years). At a median follow-up of 12 months, the objective response rate to ipilimumab and nivolumab was 20%. The median progression-free survival while on ipilimumab and nivolumab was 4 months (range, 0.8-19 months). Immune-related adverse events (irAEs) of any grade with ipilimumab and nivolumab were recorded in 29 (64%) of the 45 patients; grade 3 irAEs were recorded in 6 (13%) of the 45 patients. CONCLUSION Ipilimumab and nivolumab demonstrated antitumor activity with acceptable toxicity in patients with metastatic RCC who had prior treatment with checkpoint inhibition.
An investigation of FDA drug recalls revealed that the five most common recall reasons were contamination, mislabeling, adverse reaction, defective product, and incorrect potency. Compounding firms were associated more frequently with contamination than were noncompounding firms.
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