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BACKGROUND: Currently, treatment options for patients with advanced melanoma who experience failed immunotherapy or targeted therapy are lacking. Recent studies suggest the antitumor activity of combined pembrolizumab and lenvatinib in patients with advanced melanoma progressing on immunotherapy. Herein, we report the clinical outcomes of combined lenvatinib and a programmed cell death protein-1 inhibitor (PD-1) in this population. MATERIALS AND METHODS: This French multicenter real-world study was conducted between September 2020 and July 2023. The primary endpoint was the objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumours (version 1.1). Secondary variables were treatment-related adverse events (TRAEs), progression-free survival (PFS), overall survival (OS), and duration of response (DOR). RESULTS: Of the 67 patients included (median age, 69 years; median follow-up, 5.0 months), 85% had stage IV-M1c or M1d disease. The overall ORR was 28.4% (95% CI, 18%-41%), including 3 complete (4.5%) and 16 partial (23.9%) responses. Median DOR was 3.1 (interquartile range, 1.3-4.3) months. Median PFS and OS were 3.1 (95% CI, 2.5-3.7) and 9.8 (95% CI, 5.6-13.9) months, respectively. Grades 3-5 TRAEs occurred in 16 (24%) patients; common TRAEs were fatigue (43.3%), nausea/vomiting (26.8%), diarrhea (20.9%), and hypertension (20.9%). No treatment-related deaths occurred. CONCLUSION: Our real-world study demonstrates an interesting response rate and acceptable safety profile in a population with poor prognostic factors. Our data support this treatment option for refractory melanoma, as it is not approved by the Food and Drug Administration or European Medicines Agency, and highlight the need for new strategies.
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Although cemiplimab has been approved for locally advanced (la) and metastatic (m) cutaneous squamous-cell carcinomas (CSCCs), its real-life value has not yet been demonstrated. An early-access program enrolled patients with la/mCSCCs to receive cemiplimab. Endpoints were best overall response rate (BOR), progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety. The 245 patients (mean age 77 years, 73% male, 49% prior systemic treatment, 24% immunocompromised, 27% Eastern Cooperative Oncology Group performance status (PS) ≥ 2) had laCSCCs (35%) or mCSCCs (65%). For the 240 recipients of ≥1 infusion(s), the BOR was 50.4% (complete, 21%; partial, 29%). With median follow-up at 12.6 months, median PFS was 7.9 months, and median OS and DOR were not reached. One-year OS was 73% versus 36%, respectively, for patients with PS < 2 versus ≥ 2. Multivariate analysis retained PS ≥ 2 as being associated during the first 6 months with PFS and OS. Head-and-neck location was associated with longer PFS. Immune status had no impact. Severe treatment-related adverse events occurred in 9% of the patients, including one death from toxic epidermal necrolysis. Cemiplimab real-life safety and efficacy support its use for la/mCSCCs. Patients with PS ≥ 2 benefited less from cemiplimab, but it might represent an option for immunocompromised patients.
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AIM: In metastatic melanoma (MM) there is an agreement that a fast or slow progression should influence the choice between drugs with immediate impact (BRAF-inh) or delayed (ipilimumab) activity. MM kinetics thus appears crucial for medical decision, although only estimated through surrogate markers (tumour load or lactate dehydrogenase (LDH)). Our objective was to show that 1-MM kinetics can be measured and 2- is a real prognostic factor. METHOD: Among all stage IV MM, we retrospectively select those with long follow-up who had two comparable total body computed tomography (CT) scans within the first 3 months, and did not receive meantime any treatment with a likely impact on MM kinetics. Kinetics index (KI) was calculated from changes in total metastatic volume (ΔTMV/ΔT). RESULTS: In 126 patients, KI of progression ranges from 0 to 24,839 mm3/day. Overall survival (OS) was significantly much lower in the higher terciles of KI than in the lower ones (median OS of 459, 388 and 183 days, for KI of 0-99, 100-999 and > or =1000 mm3/day, respectively). In the multivariate analysis, KI was more predictive of OS than LDH or tumour load. CONCLUSION: Delaying major treatments in stage IV MM for a few weeks permits a measure of KI, which is the best prognostic indicator in MM. The huge range of KI probably reflects major differences in aggressiveness that any therapeutic decision should take into account. KI could be used to assess prospectively how much the efficacy of each new MM drugs is influenced by MM initial kinetics.