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BACKGROUND: Colitis was the third most common immune-related adverse effect in melanoma patients treated with immune-checkpoint inhibitor (ICI). With the limitation of real-world data in the UK population, this study was conducted in a UK hospital where a fresh colitis guidance was introduced to evaluate the overall grading (OG) to assess colitis severity and guide the treatment. AIMS: This study aimed to investigate colitis severity by Common Terminology Criteria for Adverse Events (CTCAE) grade and overall grade at time of presentation. Colitis treatment and outcome were evaluated to compare the impact of these two categories. METHODS: A single-center, retrospective observational study was performed in melanoma patient developing colitis symptoms. RESULTS: A total of 44 advanced melanoma patient with colitis symptoms were included. Median time to colitis onset was 67 days (range 4-890). Majority of patients developed G1/ G2 of CTCAE scale (70.4%) but moderate or severe overall grade (84.1%). There were 65.9% of patients treated with steroids, and 38.2% with infliximab and 4.5% with vedolizumab. The median time of colitis resolution was 28 days (range 0-282). Both treatment modality and time to resolution were associated with severity of colitis assessed by complete OG(p<0.0001) rather than CTCAE grading (p>0.05). CONCLUSIONS: This study provided a comprehensive description about ICI-induced colitis management in a single center of the UK. The more completed OG was proposed to stratify colitis patient and guide the investigation and treatment decision at presenting time, replacing the old CTCAE grading.
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AIMS: The MAPK pathway is constitutively activated in uveal melanoma (UM). Selumetinib (AZD6244, ARRY-142886), a MEK inhibitor, has shown limited activity as monotherapy in metastatic UM. Pre-clinical studies support synergistic cytotoxic activity for MEK inhibitors combined with taxanes, and here we sought to assess the clinical efficacy of combining selumetinib and paclitaxel. PATIENTS AND METHODS: Seventy-seven patients with metastatic UM who had not received prior chemotherapy were randomised to selumetinib alone, or combined with paclitaxel with or without interruption in selumetinib two days before paclitaxel. The primary endpoint was progression free survival (PFS). After amendment, the combination arms were combined for analysis and the sample size adjusted to detect a hazard ratio (HR): 0.55, 80% power at 1-sided 5% significance level. RESULTS: The median PFS in the combination arms was 4.8 months (95% CI: 3.8 - 5.6) compared with 3.4 months (2.0 - 3.9) in the selumetinib arm (HR 0.62 [90% CI 0.41 - 0.92], 1-sided p-value = 0.022). ORR was 14% and 4% in the combination and monotherapy arms respectively. Median OS was 9 months for the combination and was not significantly different from selumetinib alone (10 months) with HR of 0.98 [90% CI 0.58 - 1.66], 1-sided p-value = 0.469. Toxicity was in keeping with the known profiles of the agents involved. CONCLUSIONS: SelPac met its primary endpoint, demonstrating an improvement in PFS for combination selumetinib and paclitaxel. No improvement in OS was observed, and the modest improvement in PFS is not practice changing.