No abstract

Results: 72 patients were included: 52 received abemaciclib as first line, 20 as second line; in 49 patients abemaciclib was administer in combination with an aromatase inhibitor, in 23 with fulvestrant. 95.8% of patients experienced at least one adverse event. The most common was diarrhea (79.2%), mainly G1 (66.7% of cases). Other common toxicities were: neutropenia (56.9%), increased serum creatinine (38.9%), anemia (37.5%), nausea (34.7%), fatigue (23.6%) and hypertransaminasemia (22.2%). Toxicities were mainly low grade; 10.1% of adverse events where G3-4. 48.6% of patients required a temporary interruption of abemaciclib and 45.8% a dose reduction. All 17 patients aged 70 required a dose reduction. A concomitant palliative radiotherapy was administered in 16 patients: in all cases radiotherapy was regularly completed; a temporary interruption of abemaciclib was required in 3 patients due to hematologic toxicities. In patients with measurable disease, ORR was 55.7%, significantly higher in first line compared to second line (70.5% vs 17.7%, p<0.001). ORR was not significantly different between full and reduced dose (46.9% vs 65.5%, p¼0.143). At the time of the present analysis, 51 patients are still on therapy. Treatment discontinuations were due to disease progression in 17 patients, and to adverse events in 4 (G3 increased ALT in 1 patient and persistent G2-3 cutaneous toxicity in 3 patients).Conclusions: In a real-world population, abemaciclib was associated with a meaningful rate of objective response, with a favourable safety profile. Side effects were mostly low grade, manageable with temporary interruptions or dose reductions.Legal entity responsible for the study: The authors.

This study aimed to assess whether dabrafenib/trametinib and vemurafenib/cobimetinib treatments are associated with a change in skeletal muscle area (SMA) and total fat-free mass (FFM) assessed by computed tomography (CT), and to compare the efficacy and safety profile of these treatments in patients with metastatic melanoma. Thirty-one patients treated with B-Raf proto-oncogene, serine/threonine kinase/MAPK extracellular receptor kinase inhibitors were included between 2016 and 2019. Eighteen patients received dabrafenib/trametinib and remaining patients received vemurafenib/cobimetinib. CT scans were performed at baseline and at 4–6 months of follow-up to measure cross-sectional areas of SMA. FFM and skeletal muscle index (SMI) values were calculated. Of the patients, including 18 treated with dabrafenib/trametinib (58.1%) and 13 with vemurafenib/cobimetinib (41.9%); 58.1% were male, 41.9% were female and median age was 52 years. A significant decrease in SMA was observed after dabrafenib/trametinib and vemurafenib/cobimetinib treatments (P = 0.003 and P = 0.002, respectively). A significant decrease in FFM values was observed after dabrafenib/trametinib and vemurafenib/cobimetinib treatments (P = 0.003 and P = 0.002, respectively). Dose-limiting toxicity (DLT) was observed in 35.9% of the patients with sarcopenia. No significant difference was seen between the dabrafenib/trametinib and vemurafenib/cobimetinib groups in median progression-free survival (PFS) (11.9 vs. 7.3 months, respectively, P = 0.28) and in median overall survival (OS) (25.46 vs. 13.7 months, respectively, P = 0.41). Baseline sarcopenia was not significantly associated with PFS or OS (P = 0.172 and P = 0.326, respectively). We found a significant decrease in SMI values determined at 4–6 months compared to the values before treatment both in dabrafenib/trametinib and vemurafenib/cobimetinib groups. DLT was similar with both treatments. Baseline sarcopenia was not significantly associated with PFS or OS.