Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Nivolumab plus ipilimumab ups survival in melanoma patients with brain mets

Tawbi HA et al. N Engl J Med. 2018 Aug 23. doi: 10.1056/NEJMoa1805453

Key clinical point: Nivolumab plus ipilimumab resulted in clinically meaningful responses and progression-free survival for melanoma patients with asymptomatic, previously untreated brain metastases.

Major finding: The reported rate of intracranial benefit was 57% of patients, including complete responses in 26%, partial responses in 30%, and stable disease for at least 6 months in 2%.

Study details: An open-label, multicenter, phase 2 study initially enrolling 101 patients with histologically confirmed melanoma and metastases to the brain.

Disclosures: The study was supported by Bristol-Myers Squibb and a grant from the National Cancer Institute. The study authors reported disclosures related to Bristol-Myers Squibb, Merck, Genentech, Novartis, MedImmune, AstraZeneca, Dynavax Technologies, Genoptix, Exelixis, Acceleron Pharma, Eisai, and others.

Read the article.


Tawbi HA et al. N Engl J Med. 2018 Aug 23. doi: 10.1056/NEJMoa1805453.


These data show that checkpoint inhibitors can be similarly effective in CNS metastases as they can be in extracranial metastases related to melanoma, according to Samra Turajlic, MD, PhD, and James Larkin, FRCP, PhD, of the Renal and Skin Units at the Royal Marsden National Health Service Foundation Trust in London.

Based on the study results, larger trials are warranted, including patients with CNS metastases from melanoma, kidney, lung, and other cancers where checkpoint inhibitors have demonstrated efficacy, Dr. Turajlic, who is also with the Translational Cancer Therapeutics Laboratory at the Francis Crick Institute in London, and Dr. Larkin wrote in an editorial.

“Such patients should no longer generally be excluded from clinical trials,” they wrote.

While the study by Dr. Tawbi and his colleagues was small, they added, its results are relevant to clinical practice because of the high rate of response, rapid response time, and side effect profile, which was manageable.

In fact, the nivolumab plus ipilimumab regimen described in this study should be considered first-line therapy for all patients who meet the study’s inclusion criteria, they asserted.

However, the results should “absolutely not” be extrapolated to higher-risk patients, such as those with leptomeningeal disease or with low performance status, which investigators excluded from the present study.

“There are good data showing that patients with cerebral metastases can be stratified into groups that have very different survival and morbidity,” Dr. Turajlic and Dr. Larkin wrote. “Caution is necessary until we have data across all the groups.”

These comment are based on an editorial in the New England Journal of Medicine (doi: 10.1056/NEJMe1807752) . Dr. Turajlic reported patents pending for an indel biomarker (PCT/GB2018/051893) and an indel therapeutic (PCT/GB2018/051892). Dr. Larkin reported disclosures related to Bristol-Myers Squibb, Novartis, Genentech, Pierre-Fabre, Incyte, and AstraZeneca.