Management of metastatic melanoma: improved survival in a national cohort following the approvals of checkpoint blockade immunotherapies and targeted therapies

Dobry, Allison S.; Zogg, Cheryl K.; Hodi, F. Stephen; Smith, Timothy R.; Ott, Patrick A.; Iorgulescu, J. Bryan

doi:10.1007/s00262-018-2241-x

Cited by 54 publications

(58 citation statements)

References 35 publications

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“…The five-year survival rate for metastatic melanoma has been 15-20% [2], although these statistics are rapidly improving with the success of immune checkpoint inhibitors. Treatment with immune checkpoint inhibitors demonstrated substantial clinical efficacy along with long-term survival outcomes in patients with advanced melanoma [3][4][5]. There are several clinical trials such as KEYNOTE-002, CheckMate067 and CheckMate064, which validate these findings, as detailed in Table 1.…”

Section: Introductionmentioning

confidence: 92%

Current Advances in the Treatment of BRAF-Mutant Melanoma

Patel

Yacoub

Mishra

et al. 2020

Cancers

117

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Melanoma is the most lethal form of skin cancer. Melanoma is usually curable with surgery if detected early, however, treatment options for patients with metastatic melanoma are limited and the five-year survival rate for metastatic melanoma had been 15–20% before the advent of immunotherapy. Treatment with immune checkpoint inhibitors has increased long-term survival outcomes in patients with advanced melanoma to as high as 50% although individual response can vary greatly. A mutation within the MAPK pathway leads to uncontrollable growth and ultimately develops into cancer. The most common driver mutation that leads to this characteristic overactivation in the MAPK pathway is the B-RAF mutation. Current combinations of BRAF and MEK inhibitors that have demonstrated improved patient outcomes include dabrafenib with trametinib, vemurafenib with cobimetinib or encorafenib with binimetinib. Treatment with BRAF and MEK inhibitors has met challenges as patient responses began to drop due to the development of resistance to these inhibitors which paved the way for development of immunotherapies and other small molecule inhibitor approaches to address this. Resistance to these inhibitors continues to push the need to expand our understanding of novel mechanisms of resistance associated with treatment therapies. This review focuses on the current landscape of how resistance occurs with the chronic use of BRAF and MEK inhibitors in BRAF-mutant melanoma and progress made in the fields of immunotherapies and other small molecules when used alone or in combination with BRAF and MEK inhibitors to delay or circumvent the onset of resistance for patients with stage III/IV BRAF mutant melanoma.

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Section: Introductionmentioning

confidence: 92%

Current Advances in the Treatment of BRAF-Mutant Melanoma

Patel

Yacoub

Mishra

et al. 2020

Cancers

117

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“…ED visits were observed in 18.0% of visits in the PEMBRO cohort and 21.0% in IPI þ NIVO; the mean (SD) number of ED visits per 1,000 patient months was 164 (36) vs 20 (40), respectively. ICU admissions were 2.0% vs 4.0%, for PEMBRO and IPI þ NIVO, respectively; the mean (SD) ICU days per 1,000 patient months was 7 (5) vs 15 (10), for PEMBRO and IPI þ NIVO, respectively (Table 4). In logistic regression analysis retaining covariates with p < .1, patients in the PEMBRO cohort had statistically .619 AIDS, n (%) 0 (0.0) 0 (0.0) -Autoimmune disease, n (%) 11 (5.5) 9 (4.5) .646 Cerebrovascular disease, n (%) 10 (5.0) 6 (3.0) .307 Congestive heart failure, n (%) 6 (3.0) 7 (3.5) .778 Connective tissue disease, n (%) 3 (1.5) 4 (2.0) 1.000 COPD, n (%) 28 (14.0) 27 (13.5) .885 Coronary artery disease, n (%) 36 (18.0) 23 (11.5) .067 Dementia, n (%) 2 (1.0) 3 (1.5) 1.000 Diabetes mellitus, n (%) 41 (20.5) 26 (13.0) .045 End organ damage from Diabetes, n (%) 1 (0.5) 0 (0.0) 1.000 Hemiplegia, n (%) 0 (0.0) 0 (0.0) -Hypertension, n (%) 9 (4.5) 8 (4.0) .804 Leukemia, n (%) 0 (0.0) 0 (0.0) -Lymphoma, n (%) 0 (0.0) 0 (0.0) -Mild liver disease, n (%) 12 (6.0) 2 (1.0) .011 Moderate-severe liver disease, n (%) 0 (0.0) 1 (0.5) 1.000 Moderate-severe renal disease, n (%) 2 (1.0) 2 (1.0) 1.000 Obesity, n (%) 1 (0.5) 0 (0.0) 1.000 Oral cancer, n (%) 1 (0.5) 0 (0.0) 1.000 Osteoarthritis, n (%) 1 (0.5) 0 (0.0) 1.000 Peptic ulcer disease, n (%) 13 (6.5) 13 (6.5) 1.000 Peripheral vascular disease, n (%) 14 (7.0) 14 (7.0) 1.000 (Figure 1).…”

Section: Hospital and Emergency Department Utilizationmentioning

confidence: 99%

“…Programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint inhibitors are the new standard of care for the treatment of patients with unresectable or metastatic melanoma, either as single agent therapy, or in combination with anti-CTLA-4 6,7 . Among checkpoint inhibitor-based regimens approved by the US Food and Drug Administration for advanced melanoma are pembrolizumab (PEMBRO) and ipilimumab with nivolumab (IPI þ NIVO), both of which are associated with improved survival and lower toxicity vs chemotherapy [8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

Hospitalization and emergency department utilization in patients with advanced melanoma receiving pembrolizumab versus ipilimumab plus nivolumab in US academic centers

Joseph

Shillington

Lee

et al. 2019

Journal of Medical Economics

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Background: Both pembrolizumab (PEMBRO) and ipilimumab þ nivolumab (IPI þ NIVO) are FDAapproved immunotherapy regimens for advanced melanoma (AM). Each regimen has different toxicity profiles potentially impacting healthcare resource utilization (HCRU). This study compared real-world hospitalization and emergency department (ED) utilization within 12 months of therapy initiation of each regimen. Methods: A retrospective cohort study was conducted in AM patients 18 years old initiating PEMBRO or IPI þ NIVO between January 1, 2016-December 30, 2017. Patients were identified from 12 US-based academic and satellite centers. All-cause hospitalization ED visits were identified. These events were used to calculate rates per 1,000 patient months. Utilization between groups was compared using multivariate logistic regression. Results: In total, 400 patients were included (200 PEMBRO, 200 IPI þ NIVO). PEMBRO vs IPI þ NIVO patients had poorer Eastern Cooperative Group (ECOG) performance status, 29% 2-4, vs 12% (p < .001); more diabetes, 21% vs 13% (p ¼ .045); were more often PD-L1 expression positive, 77% vs 63% (p ¼ .011); and less likely BRAF mutant, 35% vs 50% (p ¼ .003). The proportion with more than one hospitalization over 12 months was 17% PEMBRO vs 24% IPI þ NIVO. Less than 2% had more than one admission and none had more than two. Unadjusted mean (SD) hospitalizations per 1,000 patient-months were 16 (37) and 20 (38), PEMBRO and IPI þ NIVO, respectively. Adjusted odds ratio for hospitalization was 0.6 (95% CI ¼ 0.3-0.9; p ¼ .027) for PEMBRO vs IPI þ NIVO. ED visits occurred in 18% vs 21%, PEMBRO and IPI þ NIVO, respectively, 0.7 (p ¼ .186). Conclusions: PEMBRO patients had a significantly lower probability of hospitalization through 12 months vs IPI þ NIVO. The probability of ED visits did not differ.

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“…These analyses evaluated the disparity in use of immunotherapy for all stages of melanoma in diagnosis years before 2013, 29 before 2014, 30 , 31 and in 2015 32 and for stage III disease. 33 These prior studies 29 , 30 , 31 , 32 , 33 indicated the presence of comorbidities, older age, government or no insurance, lower educational and income levels, and treatment at a community practice as factors associated with decreased receipt of immunotherapy. Our study further supports that many of these prior demographic factors may be associated with receipt of immunotherapy with the addition of cases diagnosed in 2015 and 2016.…”

Section: Discussionmentioning

confidence: 99%

Association of Sociodemographic Factors With Immunotherapy Receipt for Metastatic Melanoma in the US

et al. 2020

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Key Points Question Are sociodemographic factors associated with likelihood of receiving immunotherapy for patients diagnosed with metastatic melanoma in the US? Findings In this cohort study of 9512 metastatic melanoma cases diagnosed between 2013 and 2016 in the National Cancer Database, factors associated with receiving immunotherapy included diagnosis in Medicaid expansion states, residence in areas with high rates of high school graduation, and treatment at academic cancer centers or integrated cancer networks. Meaning This study found that patients with metastatic melanoma diagnosed in Medicaid expansion states, treated at academic or integrated cancer centers, and living in high graduation–rate areas were more likely to receive immunotherapy.

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Management of metastatic melanoma: improved survival in a national cohort following the approvals of checkpoint blockade immunotherapies and targeted therapies

Cited by 54 publications

References 35 publications

Current Advances in the Treatment of BRAF-Mutant Melanoma

Current Advances in the Treatment of BRAF-Mutant Melanoma

Hospitalization and emergency department utilization in patients with advanced melanoma receiving pembrolizumab versus ipilimumab plus nivolumab in US academic centers

Association of Sociodemographic Factors With Immunotherapy Receipt for Metastatic Melanoma in the US

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