Lung Cancer最新文献

Objectives: The objective of our study was to benchmark the incidence and severity of lorlatinib-related weight gain and dyslipidaemia in a real-world context, to guide future therapeutic strategies to mitigate these toxicities.

Methods: We conducted a retrospective, observational analysis of patients with ALK and ROS1-positive NSCLC at a single institution in the UK who were commenced on lorlatinib from 11/2016 to 11/2022. Non-small cell lung cancer (NSCLC) patients prescribed lorlatinib were identified through institutional electronic pharmacy records. Descriptive analyses were conducted. Patients without recorded baseline weight were excluded from the analysis. Changes in weight, body mass index (BMI), triglycerides, and total/low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol were calculated from serial measurements and graded in accordance with CTCAE v5.0.

Results: 43 patients were evaluated. 81 % of patients developed weight gain on lorlatinib (median: 4.5 kg, 6.5 % increase from baseline); Grade < 1 in 37 % (n = 16/43), Grade 1 in 23 % (n = 10/43), Grade 2 in 12 % (n = 5/43), and Grade ≥ 3 in 9 % (n = 4/43). BMI increase was observed in 79 % of patients. 35 % of patients with healthy baseline BMI moved into overweight/obese categories. Of patients with recorded baseline lipid levels, 91 % developed increase in total cholesterol, and 68 % an increase in triglycerides, respectively. 7 % (n = 1/15) patients with normal baseline total cholesterol developed Grade ≥ 3 elevated cholesterol; no patients with normal baseline triglycerides developed Grade ≥ 3 elevated hypertriglyceridaemia (n = 12). Median time to onset of total cholesterol elevation was 21 days. Lipid-lowering therapy was required in most patients (86 %). One patient developed a non-ST elevation myocardial infarction (NSTEMI) which may have been attributable to lorlatinib.

Conclusion: Weight gain and dyslipidaemia are commonly observed with lorlatinib, highlighting the need for effective pharmacologic and non-pharmacologic strategies to manage these toxicities. Rates were similar to those reported in the CROWN trial. Given the 60 % 5-year progression-free survival (PFS) demonstrated in CROWN, mitigation of treatment-related toxicities is paramount to minimise impact on patient quality of life (QOL) and cancer-independent morbidity in this subgroup of NSCLC patients with favourable outcomes.

Background: Clinical trials are designed to minimize factors capable of influencing patient outcomes beyond the specific diseases and treatments being studied; however, exclusion of prior cancer (PC) patients could potentially affect the generalizability of study results. We attempted to create a real-world proxy of recent immunotherapy trials in stage III and IV Non-Small Cell Lung Cancer (NSCLC) to understand the relevance of a PC history using the National Cancer Database.

Methods: Patients diagnosed between 2017 and 2020 were stratified by the presence of a prior cancer history and propensity matched to compare receipt of immunotherapy with those who did not. We analyzed overall survival using Kaplan Meier analysis and Cox proportional hazards models.

Results: The addition of immunotherapy to a regimen of chemotherapy and radiation was associated with superior survival whether stage III NSCLC patients had a PC history (HR): 0.65 (95% CI 0.59, 0.71) or had no PC history (HR:0.69 95% CI: 0.66, 0.72). The addition of immunotherapy was also associated with superior survival for stage IV patients with a PC history (HR) 0.78 95% CI 0.72, 0.85) or without PC history (HR:0.75 95% CI: 0.73, 0.78).

Discussion: Examination of real-world outcomes of two practice-changing trial regimens found the innovative treatment approach to be superior, regardless of patient PC history. Risk for a second malignancy is a reality of improving cancer treatment, thus, to individualize treatment for patients based on their personal and tumor attributes, cancer survivors will need to be included in trials.