The real-world impact of modern treatments on the survival of patients with metastatic melanoma

Donia, Marco; Ellebæk, Eva; Øllegaard, Trine Heide; Duval, Lone; Aaby, J.B.; Højberg, L.; Køhler, Ulrich Heide; Bastholt, Lars; Svane, Inge Marie

doi:10.1093/annonc/mdy289.035

Cited by 12 publications

(24 citation statements)

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“…However, a substantial proportion of patients did not benefit from these therapies and were non‐responders. We found that patients receiving ICIs experienced a prognosis comparable to patients in previous clinical trials and with published data from Nordic real‐world populations, whereas patients treated with MAPKis experienced inferior PFS and OS than expected 4,17‐21 . However, a small proportion of these patients received 2nd‐ and 3rd‐line therapies and OS may therefore not describe the outcome of 1st‐line therapies.…”

Section: Discussionsupporting

confidence: 70%

Impact of modern systemic therapies and clinical markers on treatment outcome for metastatic melanoma in a real‐world setting

Krakowski

Bottai

Häbel

et al. 2020

Acad Dermatol Venereol

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BackgroundThe survival in metastatic melanoma has dramatically improved after the introduction of immune checkpoint‐ (ICIs) and MAPKinase inhibitors (MAPKis).ObjectiveOur aim was to describe therapy response and survival in a real‐world population as well as to assess the associations between clinical variables and therapy outcome for patients with metastatic melanoma receiving first‐line ICIs or MAPKis.MethodsA total of 252 patients with metastatic (stage IV) melanoma were prospectively followed between 1 January 2010 and 3 December 2017 with follow‐up until 31 March 2019, at the Karolinska University Hospital, Sweden. Hazard ratios (HRs) for progression‐free survival (PFS) and overall survival (OS) were analysed with Cox regression, and logistic regression was used to estimate odds ratios (ORs) for therapy response.ResultsPatients receiving ICIs (n = 138) experienced longer PFS compared to patients that received MAPKis (n = 114; median PFS for ICIs was 6.8 months, and median PFS for MAPKis was 5.3 months). In the multivariable analyses of clinical markers, increasing M‐stage (OR 0.65; 95% CI 0.45–0.94; P = 0.022) and male sex (OR 0.41; 95% CI 0.19–0.90; P = 0.027) were significantly associated with lower response to ICIs. Lower baseline albumin levels (OR 0.90; 95% CI 0.83–0.98; P = 0.019) and male sex (OR 0.33; 95% CI 0.12–0.93; P = 0.036) were related with lower response to MAPKis. For ICIs, increasing M‐stage (HR 1.34; 95% CI 1.07–1.68; P = 0.010), increasing LDH (HR 1.73; 95% CI 1.19–2.50; P = 0.004) and decreasing albumin (HR 1.06; 95% CI 1.01–1.10; P = 0.011) were significantly associated lower PFS in the adjusted model. The corresponding markers for MAPKis were increasing LDH (HR 1.44; 95% CI 1.08–1.92; P = 0.013) and decreasing albumin (HR 1.05; 95% CI 1.02–1.09; P = 0.005) for PFS.ConclusionICIs and MAPKis were effective in this real‐world population, and we could confirm the importance of previously reported clinical prognostic markers. Albumin values may be associated with therapy outcome but need further validation.

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Section: Discussionsupporting

confidence: 70%

Impact of modern systemic therapies and clinical markers on treatment outcome for metastatic melanoma in a real‐world setting

Krakowski

Bottai

Häbel

et al. 2020

Acad Dermatol Venereol

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“…However, given promising clinical trial results for targeted therapy, and the relatively high rates of ''chemotherapy'' use in the subset of patients in our trial who received immune therapies, we expect that BRAFi/MEKi also contributed to the improvements in survival we saw in our trial. Supporting this, a smaller retrospective study with drug-specific data available recently evaluated patients with metastatic melanoma in Denmark and found that patients diagnosed in 2016 had improved outcomes compared with those diagnosed in 2014 or 2012 as well as increasing use of both anti-PD-1 and BRAF/ MEKi therapy [21]. Their results support our findings that the use of immune therapy and targeted therapies has led to improved overall survival.…”

Section: Discussionsupporting

confidence: 83%

Overall Survival Improved for Contemporary Patients with Melanoma: A 2004–2015 National Cancer Database Analysis

et al. 2020

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Introduction: Since 2011, encouraging clinical trial results have led to approval of multiple new therapies for advanced melanoma, but the impact of these therapies outside of trial populations is largely unknown. This study examines use of novel therapies and survival in contemporary patients with melanoma. Methods: Stage I-IV melanoma patients were identified in the 2004-2015 National Cancer Database and grouped into historic (2004-2010) and contemporary (2011-2015) cohorts. Overall survival (OS) was compared using Kaplan-Meier and Cox proportional hazard modeling adjusting for patient, tumor, and facility characteristics. Results: Of 268,668 patients, 136,828 were classified as historic and 131,840 as contemporary. Among all stages, immunotherapy utilization was significantly higher among contemporary patients (5.3% vs. 5.1%, p = 0.006). Adjusted OS was improved in the contemporary cohort (hazard ratio [HR]: 0.90 p \ 0.001). There was no difference in OS among stage I/II patients between groups (HR: 0.99, p = 0.63), while OS was significantly improved for contemporary stage III/IV patients (HR: 0.85, p \ 0.001). Among stage III/IV patients who received immunotherapy, OS was improved for the contemporary cohort (HR: 0.87, p = 0.014). Conclusions: Adjusted overall survival for contemporary melanoma patients is improved. This effect is driven by improvements for those with advanced stage disease, particularly those that received immunotherapy and BRAF/MEK targeted therapies.

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“…It is important to estimate the clinical benefit of systemic treatment in ineligible patients to decide whether possible treatment benefit is worth the risk of side-effects for individual patients and the financial burden for society. Donia et al 2,3 found that the We attempted to estimate the magnitude of the benefit from systemic treatment by comparing our study cohort to a surrogate control group from the DMTR. This surrogate control group was comprised of patients comprised of both systemically treated and untreated ineligible patients diagnosed in 2013 when only chemotherapy, ipilimumab and BRAF-inhibitors (dabrafenib and vemurafenib) monotherapy were available as standard treatments outside a trial setting.…”

Section: Clinical Benefitmentioning

confidence: 99%

Real-world outcomes of advanced melanoma patients not represented in phase III trials.

Ismail

Zeijl

Wreede

et al. 2020

JCO

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10042 Background: A large proportion of patients with advanced melanoma is not represented in phase III clinical trials, due to ineligibility. Real-world efficacy evidence of immune- and targeted therapies in these patients is lacking. We aimed to provide insight in survival outcomes of systemically treated patients who were not represented in the phase III trials in order to support clinical decision-making. Methods: Systemically treated ineligible patients with advanced melanoma diagnosed between 2014-2017 were analyzed. Prognostic importance of factors associated with overall survival (OS) was assessed by Kaplan Meier method, Cox regression models, predicted OS probabilities of prognostic subgroups and a conditional inference survival (decision) tree. Results: Of 2,536 systemically treated patients with advanced melanoma, 1,004 (40%) patients were ineligible for phase IIII trials. Ineligible patients had a poorer median OS (mOS) compared to eligible patients (8.8 vs 23 months). Eligibility criteria most strongly correlated with survival in ineligible systemically treated patients with ECOG Performance Score (PS) ≥2 vs PS 0-1 (HR 1.95 (95%CI: 1.52-2.5)), symptomatic brain metastases (BM) vs absent BM (HR 1.71 (95%CI: 1.34-2.18)) and LDH > 500 U/l vs normal (HR 1.89 (95%CI: 1.49-2.41)). All other factors for ineligibility were not associated with OS. By combining ECOG PS, BM and LDH, 18 subgroups were created. The 3-year survival probability of patients with ECOG PS ≤1, asymptomatic BM and normal LDH was 35.1%. Patients with ECOG PS of ≥2 with or without symptomatic BM had a mOS of 6.5 and 11.3 months and a 3-year survival probability of 9.3% and 23.6% respectively. In the decision tree, the covariate with the strongest predictive distinctive character for survival was LDH, followed by ECOG PS. Prognosis of LDH of > 500 U/L is infaust, although still long-term survival is possible (3-year survival probability of 15.3%). The decision tree showed the prognosis of patients with symptomatic BM can be good if ECOG PS is 0 and patients are aged ≤55 years (mOS of 22.3 months). Conclusions: Patients with advanced melanoma not represented in phase III trials treated with systemic therapy can achieve long term survival. LDH was the strongest predictive factor associated with survival, followed by ECOG PS and symptomatic BM. Other factors for ineligibility were not associated with OS. These results, together with the decision tree, can be used to provide insight in outcomes to facilitate the shared decision-making process when comparative studies are not available.

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The real-world impact of modern treatments on the survival of patients with metastatic melanoma

Cited by 12 publications

References 0 publications

Impact of modern systemic therapies and clinical markers on treatment outcome for metastatic melanoma in a real‐world setting

Impact of modern systemic therapies and clinical markers on treatment outcome for metastatic melanoma in a real‐world setting

Overall Survival Improved for Contemporary Patients with Melanoma: A 2004–2015 National Cancer Database Analysis

Real-world outcomes of advanced melanoma patients not represented in phase III trials.

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