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BACKGROUND: Data are sparse concerning the sequential use of multiple anaplastic lymphoma kinase (ALK) inhibitors for ALK-positive locally advanced or metastatic non-small cell lung cancer (NSCLC). OBJECTIVE: This study investigated sequencing and outcomes among patients receiving multiple ALK inhibitors. PATIENTS AND METHODS: This was a retrospective observational cohort study of adult patients with ALK-positive NSCLC treated with available first- and second-generation ALK inhibitors from 1 September 2011 to 31 December 2017. Duration of therapy (DOT) and overall survival (OS) were assessed with the Kaplan-Meier method. A multivariable linear regression analysis was performed to assess if DOT with a preceding ALK inhibitor was predictive of DOT for subsequent ALK inhibitor treatments. RESULTS: A total of 410 patients were analyzed: 57% received 1 ALK inhibitor; 35%, 2 ALK inhibitors; and 8%, 3-4 ALK inhibitors. Among those receiving > 1 ALK inhibitor (n = 177), 60% received a crizotinib-led sequence and 39% an alectinib-led sequence. Nearly 60% of the overall population received chemotherapy prior to their first ALK inhibitor. Median OS for the study population was 28 months, 15 months in patients who received 1 ALK inhibitor, 42 months in patients who received 2 ALK inhibitors, and 56 months in patients who received 3-4 ALK inhibitors. Longer DOT of the first ALK inhibitor was associated with increased DOT of the second (p < 0.0001), and longer DOT of the second ALK inhibitor was associated with increased DOT of the third (p < 0.0001). CONCLUSIONS: This study provides initial information on real-world treatment patterns following the introduction of new ALK inhibitors, and supports the use of sequential ALK therapies.
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Aim: To evaluate the real-world impact of brain metastases (BM) among patients with EGFR mutation-positive (EGFRm) metastatic non-small-cell lung cancer (NSCLC). Materials & methods: This retrospective, observational matched cohort electronic health record study assessed adults with EGFRm metastatic NSCLC with/without BM. Results: Among 402 patients split equally between both cohorts (±BM), the majority were Caucasian (69%), female (65%) and with adenocarcinoma (92%). Overall symptom burden and ancillary support service use were higher and median overall survival from metastatic diagnosis was significantly shorter in BM patients (11.9 vs 16 months; p = 0.017). Conclusion: BM in EGFRm NSCLC patients can negatively impact clinical outcomes. New targeted therapies that can penetrate the blood-brain barrier should be considered for treating these patients.
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Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Mutación , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Costo de Enfermedad , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Femenino , Humanos , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios RetrospectivosRESUMEN
PURPOSE: Daratumumab was initially approved by the US Food and Drug Administration to be given intravenously over the course of several hours during each administration. Because the duration of the first dose can exceed 7 h, the US Oncology Network developed a split first dose schedule to administer the first administration (dose) over 2 consecutive days. METHODS: This trial was a retrospective cohort study of adult multiple myeloma (MM) patients who initiated daratumumab within the US Oncology Network between November 1, 2015, and June 30, 2017. Descriptive analyses were conducted to compare split dose versus single-dose groups, and a multivariable linear regression model was developed to identify factors associated with total administration time. FINDINGS: In total, 622 patients were included in the analysis (364 split first dose patients and 258 single-dose patients). Infusion reactions to the first administration were documented for 47.8% of split first dose patients and 48.3% of single-dose patients. Among the total study population, the most common reactions were lower respiratory tract-related reactions (26.1%), upper respiratory tract-related reactions (17.2%), and gastrointestinal adverse events (12.5%), with no statistically significant differences between groups. The median infusion duration was 4.5 h for day 1 of the split first dose and 6.5 h for the single dose (P < 0.0001); the total median infusion time was 8.7 h for the split first dose. In multivariable regression, the only factor associated with infusion time was dosing schedule. IMPLICATIONS: These results provide real-world evidence regarding the safety and infusion time of the first infusion of daratumumab. Although the total administration time was longer among patients receiving a split first dose, the shorter day 1 infusion for this dosing schedule without increased infusion reactions may be an option for community oncology clinics.