Molecular Characterization of Inflammatory Tumors Facilitates Initiation of Effective Therapy

Inflammatory myofibroblastic tumor (IMT) is a rare, mesenchymal tumor that has an increased incidence in childhood. Tumors are usually isolated to the chest, abdomen, and retroperitoneum, but metastatic presentations can be seen. Presenting symptoms are nonspecific and include fever, weight loss, pain, shortness of breath, and cough. Approximately 85% of IMTs harbor actionable kinase fusions. The diagnosis can be delayed because of overlapping features with inflammatory disorders, such as elevated inflammatory markers, increased immunoglobin G levels, fever, weight loss, and morphologic similarity with nonmalignant conditions. We present a girl aged 11 years with a TFG-ROS1 fusion–positive tumor of the lung that was initially diagnosed as an immunoglobin G4–related inflammatory pseudotumor. She underwent complete left-sided pneumonectomy and later recurred with widely metastatic disease. We then report the case of a boy aged 9 years with widely metastatic TFG-ROS1 fusion–positive IMT with rapid molecular diagnosis. In both children, there was an excellent response to oral targeted therapy. These cases reveal that rapid molecular testing of inflammatory tumors is not only important for diagnosis but also reveals therapeutic opportunities. Targeted inhibitors produce significant radiologic responses, enabling potentially curative treatment approaches for metastatic ROS1 fusion IMT with previously limited treatment options. Primary care pediatricians and pediatric subspecialists have a crucial role in the early consultation of a pediatric oncology center experienced in molecular diagnostics to facilitate a comprehensive evaluation for children with inflammatory tumors.

Impact of Oral Targeted Therapy on the Economic Burden of Chronic Lymphocytic Leukemia in Canada

Background: Continuous oral targeted therapy (OTT) for chronic lymphocytic leukemia (CLL) represents an effective therapy but also a major economic burden on the healthcare system. This study aimed to estimate future direct costs, along with the prevalence, of CLL in the era of continuous OTT in Canada. Methods: The economic burden of OTT was modelled and compared to chemoimmunotherapy (CIT), for CLL treatment. The burden was assessed/projected from 2011 to 2025. For the OTT scenario, CIT was considered the standard of care before 2015, while OTT was considered standard of care for patients with either unmutated immunoglobulin heavy-chain variable (IGHV) or del(17p)/TP53 mutations starting in 2015 and, from 2020 onwards, for all first-line treatments except for patients with mutated IGHV. A Markov model was developed including four health states: watchful-waiting, first-line treatment, relapse and death. Costs of therapy, follow-up/monitoring and adverse events were included. Key clinical parameters were extracted from pivotal clinical trials. Results: As incidence rates and rate of survival are increasing, the prevalence of CLL in Canada is projected to increase 1.8-fold, from 8301 patients in 2011 to 14,654 by 2025. Correspondingly, the total annual costs of CLL management are predicted to increase 15.7-fold, from $60.8 million to $957.5 million during that same period. Conclusions: Although OTT enhances survival for patients with CLL, it is nonetheless associated with an important economic burden due to the projected vast increase in costs from 2011 to 2025. Changes in clinical strategies, such as implementation of a fixed OTT treatment duration, could help alleviate financial burden.

Identification of factors associated with aggressive end-of-life antitumour treatment: retrospective study of 1282 patients with cancer

ObjectiveAntitumour treatment in the last 2 weeks of death (ATT-W2) and a new regimen of ATT within 30 days of death (NATT-M1) are considered as aggressive end-of-life (EOL) care. We aimed to assess factors associated with inappropriate use of antitumour treatment (ATT) at EOL.MethodsData of patients with cancer who died in 2013, 2015, 2017 and 2019 in a single for-profit cancer centre were retrospectively analysed. ATT was divided into chemotherapy (CT), oral targeted therapy (OTT), hormonotherapy and immunotherapy (IMT).ResultsA total of 1282 patients were included. NATT-M1 was given to 197 (15.37%) patients, and 167 (13.03%) had an ATT-W2. Patients with a performance status of <2 and treated with CT had more both ATT- W2 (OR=2.45, 95% CI 1.65 to 3.65, and OR=10.29, 95% CI 4.70 to 22.6, respectively) and NATT-M1 (OR=2.01, 95% CI 1.40 to 2.90, and OR=8.41, 95% CI 4.46 to 15.86). Predictive factors of a higher rate of ATT-W2 were treatment with OTT (OR=19.08, 95% CI 7.12 to 51.07), follow-up by a medical oncologist (OR=1.49, 95% CI 1.03 to 2.17), miscellaneous cancer (OR=3.50, 95% CI 1.13 to 10.85) and length of hospital stay before death of <13 days (OR=1.92, 95% CI 1.32 to 2.79). Urinary tract and male genital cancers received less ATT-W2 (OR=0.38, 95% CI 0.16 to 0.89, and OR=0.40, 95% CI 0.16 to 0.99) and patients treated by IMT or with age <69 years more NATT-M1 (OR=19.21, 95% CI 7.55 to 48.8, and OR=1.69, 95% CI 1.20 to 2.37). Patients followed up by the palliative care team (PCT) had fewer ATT-W2 and NATT-M1 (OR=0.49, 95% CI 0.35 to 0.71, and OR=0.42, 95% CI 0.30 to 0.58).ConclusionsMost recent ATT and access to a PCT follow-up are the two most important potentially modifiable factors associated with aggressive EOL in patients with cancer. Early integrated palliative oncology care could help to decrease futile ATT at EOL.

Impact of dosing frequency (once daily or twice daily) on patient adherence to oral targeted therapies for hematologic malignancies: a retrospective cohort study among managed care enrollees

Purpose Existing studies evaluating patient adherence to oral targeted therapies such as tyrosine kinase inhibitors focus on small populations with single malignancies. This study evaluated patterns of use of oral agents in a larger population across multiple hematologic malignancies. Methods Adult patients diagnosed with a hematologic malignancy and prescribed oral targeted therapy between 2011 and 2016 ( N = 18,976) were identified from the MarketScan Commercial Claims and Encounters, and Medicare Supplemental databases. Eligible patients were enrolled in monthly prescription plans 6 months before and 12 months after the index date (date of first prescription claim; n = 2442). Multivariable logistic regressions were used to determine predictors of adherence using the medication possession ratio (MPR) and persistence through prescription refill gaps. Results The overall median adherence was 0.9 (MPR ≥ 80%) and was comparable between once-daily (QD) and twice-daily (BID) groups. Overall, 59% of patients were persistent at 12 months. Patients on QD and BID products did not have any significant differences in adherence (fixed-interval MPR, odds ratio 0.94; 95% confidence interval (CI), 0.75–1.18) or persistence (odds ratio 0.93; 95% CI, 0.75–1.17) 12 months from index. Significant predictors of adherence and persistence included patient age, total inpatient admissions, number of adverse events, and total hospital visits. Conclusion Patient-specific clinical factors, rather than regimen-specific factors, were the main predictors of oral targeted therapy adherence and persistence. Adherence to oral targeted therapies appears to be similar for patients on QD and BID regimens in the real-world setting.

Patient Adherence and Persistence to Oral Targeted Therapies for Hematologic Malignancies: A Retrospective Cohort Study Among Managed Care Enrollees

Existing studies evaluating patient adherence to oral targeted therapies such as tyrosine kinase inhibitors focus on small populations with single malignancies. This study evaluated patterns of use of oral agents in a larger population across multiple hematologic malignancies. Adult patients diagnosed with a hematologic malignancy and prescribed oral targeted therapy between 2011 and 2016 (N = 18,976) were identified from the MarketScan Commercial Claims and Encounters, and Medicare Supplemental databases. Eligible patients were enrolled in monthly prescription plans 6 months before and 12 months after index date (date of first prescription claim) (n = 2,442). Multivariable logistic regressions were used to determine predictors of adherence using the medication possession ratio (MPR), and persistence through prescription refill gaps. The overall median adherence was 0.9 (MPR ≥ 80%) and was comparable between once-daily (QD) and twice-daily (BID) groups (Table). Overall, 59% of patients were persistent at 12 months (Table). Patients on QD and BID products did not have significant differences in adherence (fixed interval MPR, odds ratio, 0.94; 95% CI, 0.75 to 1.18) or persistence (odds ratio, 0.93; 95% CI, 0.75 to 1.17) 12 months from index (Figure). Significant predictors of adherence and persistence included patient age, total inpatient admissions, number of adverse events and total hospital visits (Figure). Patient-specific clinical factors, rather than regimen-specific factors, were the main predictors of oral targeted therapy adherence and persistence. Adherence to oral targeted therapies appears to be similar for patients on QD and BID regimens in the real-world setting. Disclosures Patel: Sunesis Pharmaceuticals: Consultancy; Pharmacyclics/Janssen: Speakers Bureau; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; Genentech: Consultancy, Speakers Bureau; Juno Therapeutics: Consultancy; Celgene: Consultancy. Sudhir:ZS Associates: Employment. Kabadi:AstraZeneca: Employment. Huang:ZS Associates: Employment; Novo Nordisk Inc: Equity Ownership; AstraZeneca: Research Funding. Porwal:ZS Associates: Employment. Thakkar:ZS Associates: Employment. Pagel:Gilead: Consultancy; Pharmacyclics, an AbbVie Company: Consultancy.