Study Identifies Shift in Incidence of Second Primary Cancers in Patients with Metastatic Melanoma


During the age of systemic immunotherapy, investigators observed a change in the incidence of second primary cancers after metastatic melanoma that included solid tumor and hematologic malignancies.

A study published in JAMA Network Open observed a shift in the incidence of second primary cancers after metastatic melanoma that specifically changed during the age of immune checkpoint inhibitors (ICIs) and most commonly manifesting as cancers of the small intestine and myeloma.

“As ICIs continue to gain approval as part of the standard-of-care treatment for multiple cancers, our findings highlight the importance of tailored monitoring approaches for patients treated with immunotherapy and further identifying potential risk factors associated with subsequent cancer development,” Weiye Deng, MD, MPH, and colleagues, wrote of their findings. “Vigilant individualized monitoring and screening for these cancers are warranted.”

In this population-based cohort study, investigators utilized the Surveillance, Epidemiology, and End Results (SEER) database to evaluate patients diagnosed with metastatic melanoma from January 2005 to December 2016. The primary end point was the development of second primary cancers in this patient population.

Of 5016 patients with metastatic melanoma, 2888 (58%) were found to be younger than 65 years at the time of diagnosis and 3441 (69%) were male.

From 2005 to 2010, standardized incidence ratios (SIRs), which was used to measure the relative risk of second primary cancer, were 3.24 (95% CI, 0.08-18.04) for small intestine cancer, 1.93 (95% CI, 1.14-3.05) for lung and bronchus cancer, 2.77 (95% CI, 1.02-6.03) for kidney cancer, and 7.29 (95% CI, 2.93-15.02) for myeloma. In the period from 2011 to 2016, SIRs were 9.23 (95% CI, 1.12-33.35), 1.54 (95% CI, 0.71-2.93), 2.66 (95% CI, 0.73-6.82), and 5.90 (95% CI, 1.61-15.10), respectively.

Among those who survived the first primary melanoma, the overall risk of developing second primary cancers was revealed to be 65% higher in the pre-ICIs period and 98% higher in the post-ICIs period compared with the overall cancer incidence rate of the general population, with SIRs of 1.65 (95% CI, 1.35-2.00) and 1.98 (95% CI, 1.57-2.45), respectively.

“Immune checkpoint inhibitor treatment improves survival in some patients, but it also causes immune-related adverse events [irAEs] that can affect healthy tissues in the body,” the authors wrote. “Our study provides insight into the changing pattern of [second primary cancers] after the introduction of ICIs and indicates the need for long-term follow-up and monitoring of [second primary cancers] in this patient population.”

Of note, the SEER database lacked detailed information on cancer risk factors, such as socioeconomic status, genetic variants, and behavior factors. Moreover, other potentially important factors that were not included in the database were differences over time in disease severity at diagnosis, differences in exposure history to environmental carcinogens, differences in overall health and comorbidities, differences in availability of and barriers to medical care, and differences in other aspects of medical care.

Further, treatment data at the individual patient level were also not available, and the investigators instead used the year of diagnosis as a proxy for the type of treatment.

“Despite these limitations, to our knowledge, this is the first study that evaluates [second primary cancers] after metastatic melanoma before and after the approval of ICIs by the FDA,” the authors wrote. “More clinical and mechanistic studies are warranted.”


Deng W, Wang Y, Liu X, et al. Assessment of trends in second primary cancers in patients with metastatic melanoma from 2005 to 2016. JAMA Network Open. 2020;3(12):e2028627. doi: 10.1001/jamanetworkopen.2020.28627

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