Immune checkpoint and MAP kinase pathway inhibitors can significantly improve long-term survival for patients with melanoma. There is limited real-world data of these regimens’ effectiveness. We retrospectively analyzed 402 patients with unresectable and metastatic melanoma between August 2013 and July 2020 treated with immune checkpoint inhibitors and MAP kinase pathway targeted therapy in Alberta, Canada. Overall survival (OS) was compared using Kaplan–Meier and Cox regression analyses. Subgroup survival outcomes were analyzed by first-line treatment regime and BRAF mutation status. Three treatment eras were defined based on drug access: prior to August 2013, August 2013 to November 2016, and November 2016 to July 2020. Across each era, there were improvements in median OS: 11.7 months, 15.9 months, and 33.6 months, respectively. Patients with BRAF mutant melanoma had improved median OS when they were treated with immunotherapy in the first line as opposed to targeted therapy (median OS not reached for immunotherapy versus 17.4 months with targeted treatment). Patients with BRAF wild-type melanomas had improved survival with ipilimumab and nivolumab versus those treated with a single-agent PD-1 inhibitor (median OS not reached and 21.2 months). Our real-world analysis confirms significant survival improvements with each subsequent introduction of novel therapies for advanced melanoma.
e22013 Background: Adjuvant immunotherapies and adjuvant targeted therapy for melanoma became available in clinical practice in 2018 in Alberta, Canada. We describe the delivery of adjuvant systemic therapy, local-regional treatment, recurrence patterns, and treatment toxicity, in tertiary academic centers. Methods: We conducted a retrospective chart review of patients who received adjuvant systemic therapy for melanoma in Alberta. Adjuvant systemic treatment options included Nivolumab, Pembrolizumab, and Dabrafenib/Trametinib. Results: From September 2017 to January 2020, 71 patients were identified. Forty-one (61%) were male with a median age of 60 years (15-88). Seven (9.8%), 26 (36.6%), 27 (38%), 4 (5.6%), and 3 (4.2%) patients were stage IIIA, IIIB, IIIC, III-unspecified, and IV, respectively. BRAF mutations were detected in 31 (50.8%) patients. The median time from last surgical procedure to start of treatment was 10.8 weeks (4-28), with a median follow up time of 12 months. Sixty-one patients (85.9%) received Nivolumab, four (5.6%) patients received Pembrolizumab, and four (5.6%) Dabrafenib/Tremetinib. Twenty-eight (87.5%) of 32 patients with a positive sentinel lymph node biopsy did not complete elective regional lymph node dissection. Only two patients received adjuvant radiation. Local-regional surveillance with regular nodal ultrasound was not consistently performed. Seven (9.8%) patients had clinical or radiographic finding of enlarged regional lymph node while on treatment. At time of analysis, thirteen (18.3%) patients have completed adjuvant therapy, 18 (25.3%) discontinued therapy, and 39 (54.9%) patients were still on treatment. Eleven (15.4%) patients discontinued treatment due to toxicity, 8 (13.1%) from Nivolumab, 3 (75%) from Dabrafenib/Trametinib. Nine (12.6%) patients relapsed on treatment, of those, five (55.5%) had incidental findings on baseline imaging. Hypothyroidism affected 11 (15.4%) patients, hypophysitis and other immune-related side effects were described in 14 (19.7%) cases. Conclusions: Our cohort reflects excellent patient selection and delivery of adjuvant therapy consistent with clinical trial data. Surgical and radiation oncology care has adapted, and differs from trial procedure. Adjuvant immunotherapy was used in most patients. There appears to be a higher rate of discontinuation due to toxicity with Dabrafenib/Trametinib. Toxicity and recurrence findings are preliminary and will be updated.
Background Anti‐programmed death‐1 (PD‐1) immunotherapy has drastically improved survival for metastatic melanoma; however, 50% of patients have progression within 6 months despite treatment. In this study, we investigated host, and tumor factors for metastatic melanoma patients treated with anti‐PD‐1 immunotherapy. Methods Patients treated with the anti‐PD‐1 immunotherapy between 2014 and 2017 were identified in Alberta, Canada. All patients had Stage IV melanoma. Patient characteristics, investigations, treatment, and clinical outcomes were obtained from electronic medical records. Results We identified 174 patients treated with anti‐PD‐1 immunotherapy. At 37.1 months median follow‐up time 135 (77.6%) individuals had died and 150 (86.2%) had progressed. An elevated lactate dehydrogenase (LDH) had a response rate of 21.0% versus 41.0% for those with a normal LDH ( p = 0.017). Host factors associated with worse median progression‐free survival (mPFS) and median overall survival (mOS) included liver metastases, >3 sites of disease, elevated LDH, thrombocytosis, neutrophilia, anemia, lymphocytopenia, and an elevated neutrophil/lymphocyte ratio. Primary ulcerated tumors had a worse mOS of 11.8 versus 19.3 months ( p = 0.042). We identified four prognostic subgroups in advanced melanoma patients treated with anti‐PD‐1 therapy. (1) Normal LDH with <3 visceral sites, (2) normal LDH with ≥3 visceral sites, (3) LDH 1‐2x upper limit of normal (ULN), (4) LDH ≥2x ULN. The mPFS each group was 14.0, 6.5, 3.3, and 1.9 months, while the mOS for each group was 33.3, 15.7, 7.9, and 3.4 months. Conclusion Our study reports that host factors measuring the general immune function, markers of systemic inflammation, and tumor burden and location are the most prognostic for survival.
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