Targeted Therapies Contribute to Significant Decline in Melanoma-Related Mortality

The mortality rate for cutaneous melanoma was significantly reduced between 2013 to 2016 as a result of new targeted therapies for metastatic disease, according to a recent report in theAmerican Journal of Public Health.¹It is the largest death decline ever recorded for skin cancer.²

“Our findings show how quickly patients and physicians accepted these new drugs because they profoundly reduce deaths from melanoma,” said co-senior study author David Polsky, MD, PhD, the Alfred W. Kopf, MD, Professor of Dermatologic Oncology at NYU Langone Health and Perlmutter Cancer Center, in a press statement. “These therapies are now considered the backbone of how we treat this cancer.”

Following 30 years of increases in cutaneous melanoma-related mortality, there was a 17.9% decrease in mortality. In the general population, the annual percent change (APC) was —6.2% (95% CI, –8.7% to –3.7%). Subset analyses showed an APC of –8.3% among men aged 50 years or older. Among women aged 50 years or older, the APC was –5.8% (95% CI, –8.9% to –2.5%). The decrease was observed across most 10-year age subsets.¹

The 4-year decline in melanoma mortality exceeds the most notable 4-year declines among other major cancers, including prostate (14%), breast (8%), lung (8%), and colon cancer (5%).

Aside from targeted therapies, education and early detection were other major causes of the decline, according to Berk-Krauss et al.

Information from the SEER database showed a decrease in tumor thickness from 0.73 mm to 0.58 mm between 1989 and 2009, but this change was considered too low to have impacted the overall decline of the incidence of melanoma-related mortality. Targeted therapies, on the other hand, have contributed to the increase in 5-year survival rates to between 30% and 50%, from a historical rate of about 10% or less. Earlier data from Dobry et al confirm the contribution of improved treatment on overall survival, which saw a 31% relative improvement in a group of 17,975 hospital-based patients with metastatic melanoma who were treated after notable FDA approvals compared with those treated in 2011.³

Previously, increases in the incidence of melanoma were observed from 1988 to 2016 and 1986 to 2013, 2014. The increase from 1988 to 2016 was most significant for White patients aged 20 years or older who experienced a 108.0% increase in incidence and an APC of 2.7% (95% CI, 2.5%-2.9%). The increase in melanoma incidence was also significant among men aged 50 years or older who at 178.4% with an APC of 3.4% (95% CI, 3.2%-3.7%) and in women aged 50 years or older at 142.1% with an APC of 3.2% (95% CI, 3.0%-3.5%). Since 2005, however, there has been an overall age-adjusted slight APC decline, from 3.2% to 1.7%.

For patients with cutaneous melanoma, overall mortality increased by 7.5% with an APC of 0.2% (95% CI, 0.1%-0.3%) between 1986 and 2013. During this period, there was an increase in mortality of 4.2% in women aged 50 years or older with an APC of 0.2% (95% CI, 0.1%-0.4%). In men aged 50 years or older, a high increase of 35.4% was observed between 1986 and 2014. This subset also had 2 statistically significant APC escalations of 1.9% (95% CI, 1.5%-2.3%) and 1.7% (95% CI, 1.1%-2.2%), during most of the period.

The report was limited by a low number of contributions from SEER sites (n = 9). However, the mortality data were reported for all 50 states.¹

To conduct the analyses for the report, Berk-Krauss et al coded incidences of melanomas of the skin per the International Classification of Diseases for Oncology, Third Edition (ICD-O-3; Geneva, Switzerland: World Health Organization; 2000), histological tumor classification. Since melanoma is rare for individuals under the age of 20, overall age-adjusted incidence rates for men and women aged 20 years or older were collected and stratified into 10-year increments. SEER*Stat was used to obtain mortality data from the National Center for Health Statistics national database death certificates. The mortality analysis was confined to White patients and stratified by age and sex, from 1986 to 2016. Finally, the Joinpoint Regression Program 4.5.01 was used to analyze incidence and mortality trends.

Research on the mortality rates in melanoma was a joint effort between researchers at the Perlmutter Cancer Center of New York University and Harvard University.²

References

1. Berk-Krauss J, Stein JA, Weber J, et al. New systematic therapies and trends in cutaneous melanoma deaths among us whites, 1986—2016.Am J Public Health. 2020;e1-e3. doi: 10.2105/ajph.2020.305567.
2. America Sees Record Lows of Deaths Due to Melanoma [news release]. New York, New York: NYU Langone Health; March 19, 2020. https://bit.ly/2JdVnzy. Accessed March 24, 2020.
3. Dobry AS, Zogg CK, Hodi FS, Smith TR, Ott PA, Iorgulescu JB. Management of metastatic melanoma: improved survival in a national cohort following the approvals of checkpoint blockade immunotherapies and targeted therapies.Cancer Immunol Immunother. 2018; 67(12):1833-1844. doi: 10.1007/s00262-018-2241-x.