Population survival impact of new targeted and immune based therapies for metastatic or unresectable melanoma

Introduction New classes of drugs for metastatic or unresectable melanoma (MM) have shown improved survival in randomized trials (e.g., anti-CTLA-4, anti-PD-1, BRAF/MEK inhibitors). We sought to describe uptake of these new drugs and their impact on population-based survival outcomes of MM. Objectives and Approach We sought to describe uptake of these new drugs and their impact on population-based survival outcomes of MM. This was a retrospective, population-based cohort study of all treated MM in Ontario 2007-2015. Administrative data sources from the Institute for Clinical Evaluative Sciences (ICES) were utilized. Within ICES, cutaneous and non-cutaneous primaries were identified in the Ontario Cancer Registry. Administrative sources from Cancer Care Ontario, Ministry of Health and Long-Term Care, and Canadian Institute for Health Information identified patients treated with palliative systemic therapy, radiotherapy and metastatectomy. Temporal trends in utilization and survival were investigated. Survival by drug class was described. Results We identified 2,793 MM patients. First treatment was systemic therapy (46%), radiotherapy (41%) or metastatectomy (14%). MM patient number increased from 270 in 2007 to 418 in 2015. Systemic treatment rose from 125 MM first treated in 2007 to 343 in 2015. New drug treatments increased from <6% of reported first-line regimens in 2007 to 82\% in 2015. 1-year and 2-year overall survival (OS) was 28% and 15% respectively for all MM in 2007-2009, rising to 46% and 35% for 2014-2015 (logrank p<0.001; adjusted hazard ratio (AHR) 0.56, 95% confidence interval (CI): (0.49,0.63)). Survival gains were largely in the subset treated primarily systemically, where new drugs were increasingly utilized (2-year OS 16% 2007-2009 vs. 44% 2014-2015 logrank p<0.001; AHR 0.46, 95% CI: (0.38,0.56)). Conclusion/Implications Utilization of systemic therapy for MM has increased considerably in routine practice during 2007-2015; at least some of this increase relates to use of novel agents since 2011. In line with randomized trial findings, new drug adoption was associated with substantial increases in population-based MM survival

Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12

PURPOSE: For patients with relapsed or refractory aggressive lymphoma, we hypothesized that gemcitabine-based therapy before autologous stem-cell transplantation (ASCT) is as effective as and less toxic than standard treatment. PATIENTS AND METHODS: We randomly assigned 619 patients with relapsed/refractory aggressive lymphoma to treatment with gemcitabine, dexamethasone, and cisplatin (GDP) or to dexamethasone, cytarabine, and cisplatin (DHAP). Patients with B-cell lymphoma also received rituximab. Responding patients proceeded to stem-cell collection and ASCT. Coprimary end points were response rate after two treatment cycles and transplantation rate. The noninferiority margin for the response rate to GDP relative to DHAP was set at 10%. Secondary end points included event-free and overall survival, treatment toxicity, and quality of life. RESULTS: For the intention-to-treat population, the response rate with GDP was 45.2%; with DHAP the response rate was 44.0% (95% CI for difference, -9.0% to 6.7%), meeting protocol-defined criteria for noninferiority of GDP (P = .005). Similar results were obtained in a per-protocol analysis. The transplantation rates were 52.1% with GDP and 49.3% with DHAP (P = .44). At a median follow-up of 53 months, no differences were detected in event-free survival (HR, 0.99; stratified log-rank P = .95) or overall survival (HR, 1.03; P = .78) between GDP and DHAP. Treatment with GDP was associated with less toxicity (P < .001) and need for hospitalization (P < .001), and preserved quality of life (P = .04). CONCLUSION: For patients with relapsed or refractory aggressive lymphoma, in comparison with DHAP, treatment with GDP is associated with a noninferior response rate, similar transplantation rate, event-free survival, and overall survival, less toxicity and hospitalization, and superior quality of life

Emergency Department Utilization for Patients Receiving Immune Checkpoint Inhibitors: A Retrospective Analysis of Identification and Outcomes for Those Presenting for Immune-Related Adverse Events

Background: Immune-related adverse events (iRAEs) are known complications of immune checkpoint inhibitors (ICIs). Early identification and management leads to improved morbidity and mortality. This study seeks to address our center&rsquo;s experience with iRAEs in the emergency department (ED). Methods: We performed a retrospective review of patients treated with ICIs in 2018 and 2019 for any indication. All diagnoses of iRAEs were recorded. For all patients who presented to the ED following administration of an ICI, we assessed whether the presenting symptoms were eventually diagnosed as an iRAE. We assessed disposition, time to initiation of corticosteroids and outcomes in these patients. Results: 351 evaluable patients were treated with an ICI, 129 patients (37%) had at least one presentation to the ED, 17 of whom presented with symptoms due to a new iRAE. New iRAE diagnoses were broad, occurred after median 2 cycles, majority irAEs were grade 3 or higher (70.6%), and two patients died due to toxicity. Twelve patients were admitted to the hospital during initial presentation or at follow-up, four required ICU care. All patients required immunosuppressive therapy, and only three were later re-challenged with an ICI. Of the patients who were admitted to the hospital, median time to first dose of corticosteroid was 30.5 h (range 1&ndash;269 h). Conclusions: Patients on ICI have a significant risk of requiring an ED visit. A notable proportion of iRAEs have their first presentation at the ED and often can present in a very nonspecific manner. A standardized approach in the ED at the time of presentation may lead to improved identification and management of these patients

Real-World Evidence of Systemic Therapy Sequencing on Overall Survival for Patients with Metastatic BRAF-Mutated Cutaneous Melanoma

Aim: To evaluate optimal systemic therapy sequencing (first-line targeted therapy (1L-TT) vs. first-line immunotherapy (1L-IO)) in patients with BRAF-mutated metastatic melanoma. Methods: Nation-wide prospective data of patients with newly diagnosed BRAF-mutated metastatic melanoma were retrieved from the Canadian Melanoma Research Network. Results: Our study included 79 and 107 patients in the 1L-IO and 1L-TT groups, respectively. There were more patients with ECOG 0&ndash;1 (91% vs. 72%, p = 0.023) in the 1L-IO group compared to the 1L-TT group. Multivariable Cox analysis suggested no OS differences between the two groups (HR 0.838, 95%CI 0.502&ndash;1.400, p = 0.500). However, patients who received 1L-TT then 2L-IO had the longest OS compared to 1L-IO without 2L therapy, 1L-IO then 2L-TT, and 1L-TT without 2L therapy (38.3 vs. 32.2 vs. 16.9 vs. 6.3 months, p &lt; 0.001). For patients who received 2L therapy, those who received 2L-IO had a trend towards OS improvement compared with the 2L-TT group (21.7 vs. 8.9 months, p = 0.053). Conclusions: Our nation-wide prospective study failed to establish any optimal systemic therapy sequencing in advanced BRAF-mutant melanoma patients. Nevertheless, we provided evidence that immunotherapy has durable efficacy in advanced BRAF-mutant melanoma patients, regardless of treatment line, and that Canadian medical oncologists were selecting the appropriate treatment sequences in a real-world setting, based on patients&rsquo; clinical and tumour characteristics