Multicenter, real-life experience with checkpoint inhibitors and targeted therapy agents in advanced melanoma patients in Switzerland

Mangana, Joanna; Cheng, Phil F.; Kaufmann, Corina; Amann, Valerie C; Frauchiger, Anna L.; Stögner, Viola A.; Held, Ulrike; Moos, Roger von; Michielin, Olivier; Braun, Ralph P.; Levesque, Mitchell P.; Goldinger, Simone M.; Dummer, Reinhard

doi:10.1097/cmr.0000000000000359

Cited by 21 publications

(23 citation statements)

References 54 publications

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“…In our study, 43% ORR and 77% DCR were noted, and 19% ORR and 65% DCR were recorded in the 1995–2005 study. All the results obtained in our study are comparable with the treatment outcomes via new therapies in other centres in Poland [ 15 – 18 ] and other studies with real-world data [ 19 – 22 ].…”

Section: Resultssupporting

confidence: 89%

Real-world treatment practice in patients with advanced melanoma

Cybulska-Stopa¹,

Piejko²,

Pacholczak³

et al. 2020

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Introduction The treatment outcomes of patients with advanced/metastatic melanoma were poor before the use of new therapeutic options. Material and methods A retrospective analysis was conducted among 287 patients with unresectable stage III and stage IV melanoma treated at the Maria Sklodowska-Curie National Research Institute of Oncology Cracow Branch, from 2013 to 2019. All enrolled patients were treated with immunotherapy (IT; consisting of pembrolizumab/nivolumab, or ipilimumab) or target therapy (TT; consisting of vemurafenib ±cobimetinib or dabrafenib ±trametinib) in at least one treatment line. Results mutation was detected in 152 (55%) patients. In general, the majority of patients (92%) were in very good or good condition (Eastern Cooperative Oncology Group [ECOG] 0 or 1). Brain metastasis was detected in 64 (22%) patients. Median OS and PFS in the experimental group from the beginning of the first-line treatment were 14.9 and 6.7 months, respectively. Across the study population, as a first-line treatment patients received IT, TT as well as CHT, and the median OS was 19.2, 12.6 and 15.9 months, respectively. Multivariate analysis confirmed that normal LDH levels, no brain metastases, ECOG 0, and objective response to the treatment were strong predictors of longer OS. For PFS, absence of brain metastases, ECOG 0, and treatment response were found to be predictive factors on multivariate analysis. Conclusions The administration of new therapies for the treatment of patients with advanced/disseminated melanoma significantly prolonged survival in this group of patients. Nevertheless, further studies should be conducted to assess the effectiveness of various sequences of treatment.

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Section: Resultssupporting

confidence: 89%

Real-world treatment practice in patients with advanced melanoma

Cybulska-Stopa¹,

Piejko²,

Pacholczak³

et al. 2020

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“…It has been hypothesized that SRT has the propensity to synergize with IT through five factors: 1) inducing immunogenic cell death by generating antigens 2) promoting antigen presentation on MHC I molecules enhancing the tumor cell killing through CD8 cytotoxic T-cells, 3) increasing bloodbrain-barrier-permeability, 4) inducing chemokines that help overcome T-cell exclusion from the metastases and 5) through the rare abscopal effect [26][27][28]. A retrospective analysis of 395 patients with advanced melanoma in Switzerland likewise showed an improved median OS for patients receiving IT compared to TT (16.7 months vs. 11.2 months) [29]. However, only few prospectively collected datasets have retrospectively investigated this potential synergy to date [24,30,31].…”

Section: Concurrent Systemic Treatment and Srtmentioning

confidence: 99%

Predicting survival in melanoma patients treated with concurrent targeted- or immunotherapy and stereotactic radiotherapy

et al. 2020

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Background: Melanoma patients frequently develop brain metastases. The most widely used score to predict survival is the molGPA based on a mixed treatment of stereotactic radiotherapy (SRT) and whole brain radiotherapy (WBRT). In addition, systemic therapy was not considered. We therefore aimed to evaluate the performance of the molGPA score in patients homogeneously treated with SRT and concurrent targeted therapy or immunotherapy (TT/IT). Methods: This retrospective analysis is based on an international multicenter database (TOaSTT) of melanoma patients treated with TT/IT and concurrent (≤30 days) SRT for brain metastases between May 2011 and May 2018. Overall survival (OS) was studied using Kaplan-Meier survival curves and log-rank testing. Uni-and multivariate analysis was performed to analyze prognostic factors for OS. Results: One hundred ten patients were analyzed. 61, 31 and 8% were treated with IT, TT and with a simultaneous combination, respectively. A median of two brain metastases were treated per patient. After a median follow-up of 8 months, median OS was 8.4 months (0-40 months). The molGPA score was not associated with OS. Instead, cumulative brain metastases volume, timing of metastases (syn-vs. metachronous) and systemic therapy with concurrent IT vs. TT influenced OS significantly. Based on these parameters, the VTS score (volume-timing-systemic therapy) was established that stratified patients into three groups with a median OS of 5.1, 18.9 and 34.5 months, respectively (p = 0.001 and 0.03).

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“…Baseline characteristics were only reported for patients receiving ICI, while survival was reported for all patients pre- and post-approval; therefore, it is uncertain if general baseline characteristics are similar between cohorts. Mangana et al compared survival between treatment types in a retrospective real-life cohort of 395 patients treated at three Swiss hospitals [ 16 ]. Median OS for their reference chemotherapy (treatment-naïve) group from 2008 to 2009 was 7.1 months, and comparable to our pre-ICI group, while treatment-naïve patients on targeted therapy or ICI from 2010 to 2014 had an mOS of 14.6 months, which is considerably higher than both the American cohort and our cohort.…”

Section: Discussionmentioning

confidence: 99%

Improved Progression-Free Long-Term Survival of a Nation-Wide Patient Population with Metastatic Melanoma

Soerensen

Ellebæk

Bastholt

et al. 2020

Cancers

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Approval of immune checkpoint-inhibitors (ICIs) and BRAF-inhibitors has revolutionized the treatment of metastatic melanoma. Although these drugs have improved overall survival (OS) in clinical trials, real-world evidence for improved long-term survival is still scarce. Clinical data were extracted from the Danish Metastatic Melanoma database. This nation-wide cohort contains data on all patients who received systemic treatment for metastatic melanoma between 2008 and 2016. Ipilimumab, the first approved ICI, was implemented as standard-of-care in Denmark in 2012. Hence, patients were divided in a pre-ICI (2008–2011) and an ICI (2012–2016) era. Patients were defined as long-term survivors if they were alive 3 years after initiation of systemic therapy. Data from 1754 patients were retrieved. Patients treated in the ICI era had an improved median OS (11.3 months, 95% confidence interval (CI) 10.3–12.3) compared with those in the pre-ICI era (median OS 8.3 months, 95% CI 7.4–9.5, p < 0.0001). A higher proportion of long-term survivors was observed in the ICI era (survivors >3 years increased from 13% to 26% and survivors >5 years increased from 9% to 21%; both p < 0.0001). For long-term survivors, known prognostic factors were equally distributed between the two periods, except that long-term survivors in the pre-ICI era were younger. For long-term survivors, 70% were without progression in the ICI era compared with 43% in the pre-ICI era (p < 0.0001). For all patients, the proportion without progression increased from 5% to 18% between the pre-ICI and the ICI era (p < 0.0001), respectively. Implementation of ICI has led to a significant increase in progression-free, long-term survival for real-life patients with metastatic melanoma.

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Multicenter, real-life experience with checkpoint inhibitors and targeted therapy agents in advanced melanoma patients in Switzerland

Cited by 21 publications

References 54 publications

Real-world treatment practice in patients with advanced melanoma

Real-world treatment practice in patients with advanced melanoma

Predicting survival in melanoma patients treated with concurrent targeted- or immunotherapy and stereotactic radiotherapy

Improved Progression-Free Long-Term Survival of a Nation-Wide Patient Population with Metastatic Melanoma

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