PCN184 ECONOMIC EVALUATION OF CHECKPOINT INHIBITORS FOR THE TREATMENT OF ADVANCED MELANOMA IN THE IRISH HEALTHCARE SETTING

Background: Immune checkpoint inhibitors (ICI) have achieved astonishing results and improved overall survival (OS) in several types of malignancies, including advanced melanoma. However, due to a peculiar type of anti-cancer activity provided by these drugs, the response patterns during ICI treatment are completely different from that with “old” chemotherapeutic agents. Objective: To provide an overview of the available literature and potentials of 18F-FDG PET/CT in advanced melanoma during the course of therapy with ICI in the context of treatment response evaluation. Methods: Morphologic criteria, expressed by Response Evaluation Criteria in Solid Tumors (RECIST), immune-related response criteria (irRC), irRECIST, and, more recently, immune-RECIST (iRECIST), along with response criteria based on the metabolic parameters with 18F-Fluorodeoxyglucose (18FFDG), have been explored. Results: To overcome the limits of traditional response criteria, new metabolic response criteria have been introduced on time and are being continuously updated, such as the PET/CT Criteria for the early prediction of Response to Immune checkpoint inhibitor Therapy (PECRIT), the PET Response Evaluation Criteria for Immunotherapy (PERCIMT), and “immunotherapy-modified” PET Response Criteria in Solid Tumors (imPERCIST). The introduction of new PET radiotracers, based on monoclonal antibodies combined with radioactive elements (“immune-PET”), are of great interest. Conclusion: Although the role of 18F-FDG PET/CT in malignant melanoma has been widely validated for detecting distant metastases and recurrences, evidences in course of ICI are still scarce and larger multicenter clinical trials are needed.

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Novel immune checkpoints beyond PD-1 in advanced melanoma

memo - Magazine of European Medical Oncology ◽

10.1007/s12254-021-00699-0 ◽

2021 ◽

Author(s):

Nina Zila ◽

Christoph Hoeller ◽

Verena Paulitschke

Keyword(s):

Clinical Trials ◽

Checkpoint Inhibitors ◽

Short Review ◽

Therapy Resistance ◽

Advanced Melanoma ◽

Immune Checkpoints ◽

Malignant Diseases ◽

Foreseeable Future ◽

Cell Responses ◽

Therapeutic Landscape

SummaryIn malignant diseases, targeting of immune checkpoints successfully changed the therapeutic landscape and helped to unleash anti-tumor T cell responses, resulting in durable clinical outcomes, but only in up to 50% of patients. The success of these therapies and the need to overcome intrinsic and acquired therapy resistance stimulated research to identify new pathways and targets. Numerous clinical trials are currently evaluating novel checkpoint inhibitors or recently developed strategies like modulating the tumor microenvironment, mostly in combination with approved therapies. This short review briefly discusses promising therapeutic targets, currently still under investigation, with the chance to realize clinical application in the foreseeable future.

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ESDR289 - The effect of immune checkpoint Inhibitors on the CD4+ T-cell population by patients with advanced melanoma and the role of these cells in immune related adverse events

10.26226/morressier.61081ff8bc981037240fe4ae ◽

2021 ◽

Author(s):

Tereza Jakovljevicova

Keyword(s):

T Cell ◽

Adverse Events ◽

Cell Population ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Advanced Melanoma ◽

Cd4 T Cell

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Evaluation of patients with surgically resected high-risk melanoma receiving adjuvant therapy in routine clinical practice in the United States.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.9577 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 9577-9577

Author(s):

Michael B. Atkins ◽

Cristina Julian ◽

Matthew H. Secrest ◽

Janet Lee ◽

Ana Maria Abajo Guijarro ◽

...

Keyword(s):

Adjuvant Therapy ◽

Checkpoint Inhibitors ◽

The United States ◽

Distant Recurrence ◽

Advanced Melanoma ◽

Stage Iii ◽

Braf Mutations ◽

Stage Iii Melanoma ◽

Resected Stage ◽

Braf Mutant

9577 Background: The management of patients with resected stage III melanoma has changed in recent years, and real-world data on recurrence patterns and adjuvant therapy responses are scarce. This study assessed adjuvant treatment patterns and outcomes in patients with advanced melanoma by BRAF status and relapse location. Methods: Patients diagnosed with stage III advanced melanoma between January 2011 and February 2020 in the nationwide Flatiron Health electronic health record–derived deidentified database were included if they were ≥18 years, received approved first-line (1L) adjuvant therapy after January 2018 with checkpoint inhibitors (CPIs; eg, nivolumab, pembrolizumab) or targeted therapies (TTs; eg, dabrafenib/trametinib), had 6 months’ follow-up and had ≥1 visit after starting adjuvant therapy (Cohort 1). Patients from Cohort 1 were included in Cohort 2 if they had a recurrence following initiation of adjuvant therapy, and those from Cohort 2 were included in Cohort 3 if they had a distant recurrence and available documented BRAF status at any time. Time to next systemic treatment (TTNT), overall survival (OS) and relapse free survival (RFS) were estimated using Kaplan-Meier (KM) methods from adjuvant therapy start (Cohort 1), first recurrence date (Cohort 2) or first distant recurrence date (Cohort 3). Results: Cohort 1 included 447 patients receiving 1L adjuvant therapy; Cohort 2 included patients after first distant (n = 47) or local (n = 35) relapse; Cohort 3 included distant-recurrent patients with tumors that were BRAF wild type (WT) (n = 22) or BRAF mutant (n = 23). The majority of patients were aged < 65 years. Across cohorts, relative use of TTs vs CPIs was similar: Cohort 1 (4.5% vs 96%), Cohort 2 (2.4% vs 98%) and Cohort 3 (2.2% vs 98%). Nivolumab was the most frequent treatment used across cohorts (84%-88%). In Cohort 1, 1- and 2-year KM probabilities for OS, RFS and TTNT were 93.5%/83.8%, 83.2%/70.6% and 84.0%/62.4%, respectively. In Cohort 2, for patients with local recurrence, 6- and 12-month OS probabilities were 93.4% and 78.8%, respectively, which were substantially higher than those for patients with distant recurrence (64.5% and 46.9%). In Cohort 3, for patients with documented BRAF mutations, 6- and 12-month OS rates from disease recurrence were 79.1% and 49.4%, respectively, which were greater than for those with BRAF-WT tumors (54.1% and 46.3%). Conclusions: Early RFS and OS outcomes for patients with surgically resected Stage III melanoma appear comparable to those reported in randomized clinical studies. The majority of patients with advanced melanoma, including patients who experienced recurrence, initiated treatment with CPIs. OS rates were numerically greater for Cohort 3 patients with BRAF-mutant tumors. Outcomes for patients with distant recurrence after adjuvant therapy remain unfavorable and represent a continued unmet medical need.

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Clinical and Molecular Characteristics Associated with Survival in Advanced Melanoma Treated with Checkpoint Inhibitors

Journal of Oncology ◽

10.1155/2018/6279871 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Sunil Badami ◽

Sunil Upadhaya ◽

Ravi Kanth Velagapudi ◽

Pushyami Mikkilineni ◽

Ranju Kunwor ◽

...

Keyword(s):

Clinical Trials ◽

Randomized Clinical Trials ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Random Effect ◽

Eastern Cooperative Oncology Group ◽

Advanced Melanoma ◽

Cochrane Library ◽

Molecular Characteristics ◽

Significant Heterogeneity

Background. We performed meta-analysis to gather more evidence regarding clinical-molecular subgroups associated with better overall survival (OS) in advanced melanoma treated with checkpoint inhibitors. Materials and Methods. We performed a systematic search of PubMed, Scopus, Cochrane Library, and clinical trial.gov. Randomized clinical trials that compared a checkpoint inhibitor (nivolumab or pembrolizumab) with investigator choice chemotherapy or ipilimumab were included in our study. Hazard ratios (HR) and confidence interval (CI) were calculated for progression-free survival (PFS) and OS for each subgroup using generic inverse model along with the random effect method. Results. A total of 6 clinical trials were eligible for the meta-analysis. OS was prolonged in wild BRAF subgroup (HR 0.65, 95% CI 0.49-0.85, p 0.002), Programmed cell death subgroup (PD-1+) (HR 0.57, 95% CI 0.41-0.80, p 0.001), and high lactate dehydrogenase (LDH) level subgroup (HR 0.60, 95% CI 0.38-0.95, p 0.03). Similarly, we found increased OS in eastern cooperative oncology group (ECOG) 1, males and age >65 years subgroups. Conclusions. Checkpoint inhibitors significantly increased OS in patients with wild BRAF, positive PD-1, and high LDH. However, results should be interpreted keeping in mind associated significant heterogeneity. The results of this study should help in designing future clinical trials.

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Comprehensive ambulatory monitoring during immunotherapy in patients with advanced melanoma: A prospective trial (CAMP-IT).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.tps1589 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. TPS1589-TPS1589

Author(s):

Milan Kos ◽

Laurien Buffart ◽

Jan Willem de Groot ◽

Hans Westgeest ◽

Wouter Dercksen ◽

...

Keyword(s):

Adverse Events ◽

Real Time ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Ambulatory Monitoring ◽

Vital Signs ◽

Advanced Melanoma ◽

Smartphone App ◽

Survival Outcomes ◽

Activity Data

TPS1589 Background: The emergence of immune checkpoint inhibitors has improved survival outcomes for patients with advanced melanoma. However, these treatment modalities are also associated with specific immune-related toxicities. These are often reversible after prompt recognition and initiation of appropriate management, but can result in severe morbidity and hamper health-related quality of life (HRQoL) if left undetected. Hence, accurate and regular monitoring of these patients is critical. Recent advances in mHealth technologies and the rapidly expanding armamentarium of wearable devices allow for real-time objective (vital signs and physical activity) data and patient-reported outcome measurement (PROMs) collection and, hence, serve this purpose. We hypothesize that collection of real-time objective data adds to the early detection of disease- and treatment-related adverse events. The primary objective of this study is to determine the feasibility of collecting real-time PROMs, vital signs, and physical activity data in advanced melanoma patients receiving immunotherapy using a comprehensive ambulatory monitoring platform (CAMP) that consists of a smartphone app, activity monitor, digital thermometer, and online dashboard for physicians. Methods: In this prospective multi-center trial, patients (n = 50) with advanced melanoma, scheduled to receive immunotherapy with immune checkpoint inhibitors, and with access to a smartphone are eligible for inclusion. Consenting patients will be asked to wear a FitBit Versa 2.0 during waking hours, collect daily temperature measurements using a Withings Smart Temporal thermometer, and answer weekly toxicity questionnaires (NCI PRO-CTCAE) using the smartphone app for the duration of the study (12 weeks). Primary outcome is feasibility in terms of (i) participation rates, (ii) wear-time, (iii) compliance rates with in-app questionnaires and temperature measurements, and (iv) satisfaction with the platform. Secondary exploratory outcomes include associations between CAMP-derived parameters and clinical outcomes: performance status (PS), HR-QoL scores (EORTC QLQ-C30 questionnaire), unplanned hospitalizations, physician-assessed adverse events, and 1-year survival outcomes. PS and HR-QoL will be rated at baseline, mid-study, and end-of-study. The occurrence of adverse events will be documented up to 12 months from baseline. Survival outcomes will be compared to a propensity score matched group from the Netherlands Cancer Registry. Accrual has started in February 2021. Clinical trial information: NL8827.

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