Immunotherapy Ups Survival Even in Melanoma With Brain Mets

Roxanne Nelson, BSN, RN

July 18, 2018

New data confirm what many oncologists have already seen in the clinic — that first-line treatment with a checkpoint inhibitor improves outcomes for patients with cutaneous melanoma and brain metastases (MBM). Such patients were excluded from early trials in melanoma with these drugs, but data are now in from use of these drugs in the clinic.

An analysis of data from the National Cancer Database (NCDB) found that use of checkpoint inhibitors in this population was associated with a 1.4-fold increase in median overall survival and an increase in the rate of 4-year survival from 11.1% to 28.1%.

"Through the use of nationwide cancer data, for the first time we can evaluate the impacts on survival that these exciting new therapies have for patients with melanoma brain metastases, highlighting the power of population data to help answer critical, but previously unanswerable, questions that we face every day in clinical practice," said study author Timothy Smith, MD, PhD, MPH, director of the Computational Neuroscience Outcomes Center at the Department of Neurosurgery at Brigham and Women's Hospital/Harvard Medical School, Boston, Massachusetts, in a statement.

The study was published online July 12 in Cancer Immunology Research.

First author Julian Bryan Iorgulescu, MD, a postdoctoral fellow in the Department of Pathology at Brigham and Women's Hospital/Harvard Medical School and the Department of Medical Oncology at the Dana-Farber Cancer Institute, told Medscape Medical News that the findings from this study "help confirm what many oncologists have known for a while in their own practice — that first-line checkpoint blockade immunotherapy's revolutionary results in other advanced melanomas also apply to melanoma patients with brain involvement."

The success of checkpoint blockade immunotherapy has changed the management of patients with advanced melanoma, but the authors note that early clinical trials either excluded or included disproportionately fewer cases of melanoma brain metastases.

As previously reported by Medscape Medical News, two studies presented at the 2017 annual meeting of the American Society of Clinical Oncology — CheckMate 204 (abstract 9507) and the Australian Anti-PD1 Brain Collaboration (ABC) study (abstract 9508) — both demonstrated a high degree of intracranial responses (50% to 60%) in patients with metastatic melanoma who received combination therapy with two checkpoint inhibitors, ipilimumab (Yervoy, Bristol-Myers Squibb) and nivolumab (Opdivo, Bristol-Myers Squibb). These responses were also reported to be durable.

But overall, the survival benefit of these therapies for MBM has not been clearly elucidated.

Improved Survival Outcomes

In this study, Igorulescu and colleagues evaluated the outcomes of patients with stage IV melanoma who presented with MBMs from 2010 to 2015. Using the NCDB, which comprises 70% of all newly diagnosed US cancers, they identified 220,439 patients with cutaneous melanoma, of whom 2753 had stage IV disease with brain metastases.

In the "post approval" era of checkpoint inhibitors, the percentage of MBM patients who received these agents as frontline therapy rose from 10.5% in 2011 to 34.0% in 2015 (P < .001). MBM patients who received first-line treatment with checkpoint inhibitors tended to be younger, have a more recent diagnosis (2015 vs 2011: odds ratio [OR], 4.95; P < .001), have fewer comorbidities (Charlson-Deyo comorbidity index score of 1 vs 0: OR, 0.65; P = .02), be insured privately (vs uninsured: OR, 2.70; P = .007) or through Medicare (vs uninsured: OR, 3.05; P = .005), or be diagnosed in New England.

Although the reasons for treatment selection were not available, Igorulescu noted that younger and healthier patients would most likely be treated for brain metastasis or be treated aggressively. "They may have also had fewer contraindications," he said.

For patients who received first-line treatment with checkpoint inhibitors, there was a 1.4-fold improvement in median overall survival (12.4 months vs 5.2 months; P < .001), as well as a 1.5-fold improvement in 4-year overall survival (P < .001). Even after adjustment for clinicopathologic factors, use of checkpoint inhibitor therapy continued to be associated with improved overall survival (hazard ratio, 0.12; 95% confidence interval, 0.03 - 0.49; P = .003).

The overall survival was even higher in patients with brain metastases only, improving to 56.4 months from 7.7 months (P < .001). The 4-year overall survival rate improved to 51.5% from 16.9%. In MBM patients with extracranial involvement, the use of these agents also improved both the median overall survival (9.6 months vs 3.9 months; P < .001) and 4-year overall survival (17.9% vs 7.0%; P < .001).

Among patients who received targeted therapy (n = 603, 27.9%) and most likely had BRAFV600-mutant MBMs, the authors note, only 9.8% (n = 59) also received treatment with checkpoint inhibitors. For those who did, there was a trend toward an improvement in median overall survival (10.5 months vs 7.8 months; P = .05).

Prospective studies are needed to evaluate these agents in the MBM population in order to better select the patients who may derive a benefit. "There are a number of ongoing clinical trials now investigating this very question in brain metastases for a number of cancer types, in addition to melanoma," said Iorgulescu.

The authors have disclosed no relevant financial relationships.

Cancer Immunol Res. Published online July 12, 2017. Abstract

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