Metastatic-Melanoma Immunotherapy May Be Tied To Increase In Second Cancers

Over a decade, the use of immune-checkpoint inhibitors (ICIs) for metastatic melanoma appears to have led to a shift in the pattern of second primary cancers, according to a population-based cohort study.

"Cancer immunotherapy has significantly improved clinical outcomes," said Dr. Wen Jiang of the University of Texas Southwestern Medical Center, in Dallas. "As a result, patients with metastatic melanoma that were previously considered as terminal now live for extended period of time. This resulted in many of these patients now increasingly being diagnosed with a second primary cancer down the road."

"Our study," he told Reuters Health by email, "showed that the advent of cancer immunotherapy has also changed how these second primary cancers manifest, in terms of the type of second cancer a survivor who was treated with immunotherapy may develop later in life."

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Dr. Jiang and his colleagues tapped into the Surveillance, Epidemiology, and End Results (SEER) database to assess differences before and after the U.S. Food and Drug Administration (FDA) first approved use of ICIs. Ipilimumab was approved in 2011 for metastatic melanoma, followed by other ICIs such as nivolumab and pembrolizumab.

The researchers used data on more than 5000 patients who were diagnosed between 2005 and 2016. From 2005 to 2010, the standardized incidence ratio (SIR) for small-intestine cancer was 3.24 and this rose to 9.23 between 2011 and 2016.

Corresponding SIRs for lung and bronchus cancer were 1.93 and 1.54 and for myeloma 7.29 and 5.90.

Compared to the general population, in those who survived the first primary melanoma in the earlier period, the overall risk of developing a second primary cancer was 65% higher. Between 2011 and 2016, this risk was 98% higher.

Thus, concluded Dr. Jiang, "the clinical implication of our study is that long-term follow-up in these cancer survivors, particularly those treated with immunotherapy would be needed to find these second primary cancers early, and provide rationale of potential screening in high-risk patients."

Dermatologist Dr. Michael A. Marchetti of Memorial Sloan Kettering Cancer Center, in New York City, was not convinced by the findings. He told Reuters Health by email that "there wasn't a robust signal to suggest a statistically or clinically significant change in the risk of second primary cancers (SPCs) in the pre- and post-ICIs periods."

"I disagree with the authors' conclusions that additional screening tests for SPCs are warranted in this population, given the low absolute risk of SPCs and the high absolute risk of all-cause death," he said.

Dr. Marchetti, who has studied metastatic melanoma and immune-checkpoint inhibitors, concluded, "Observational studies like these suffer from many limitations, as the authors pointed out, and analyses of the incidence rates of some individual second primary cancers were particularly limited by small numbers of observed cases."

—David Douglas

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