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Does Adding Ipilimumab to Nivolumab Improve Cancer Outcomes?


For advanced cancers other than melanoma, adding ipilimumab to nivolumab does not improve survival over nivolumab alone, but it does increase clinical and financial toxicity. 


  • Adding ipilimumab to standard-dose nivolumab improves progression-free and overall survival in advanced melanoma.

  • Ipilimumab plus nivolumab is assumed to have the same benefit in other advanced cancers and is approved for many, but the comparative efficacy of the combination over nivolumab alone has not been well established.

  • To address the issue, investigators conducted a meta-analysis of eight randomized clinical trials with 1727 patients that compared the combination to standard-dose nivolumab (3 mg/kg or 240 mg) monotherapy for advanced cancers other than melanoma.

  • Tumors included small cell lung cancer, non–small cell lung cancer, squamous cell lung cancer, mesothelioma, urothelial carcinoma, esophagogastric carcinoma, sarcoma, and glioblastoma multiforme.


  • Compared with nivolumab alone, nivolumab plus ipilimumab was not associated with improved overall survival (pooled hazard ratio [HR], 0.95; 95% CI, 0.85-1.06); in fact, four of the eight studies in the meta-analysis found patients receiving the combination had shorter median overall survival.

  • Nivolumab plus ipilimumab was associated with marginal, but not clinically meaningful, improvements in progression-free survival (PFS) over nivolumab alone (pooled HR, 0.88; 95% CI, 0.79-0.98; P = .02).

  • The combination was associated with significantly higher treatment-related grade 3 to 4 adverse events (pooled odds ratio [OR], 1.84) and treatment-related discontinuations (pooled OR, 1.96).

  • Individual grade 3 to 4 adverse events occurred much more frequently in the combination group — hepatotoxicity (9.7% vs 3%), gastrointestinal toxicity (4.0% vs 1%), pneumonitis (3.6% vs 1.5%), endocrine dysfunction (3.4% vs 0.2%), and fatigue (3.2% vs 1.7%).


“These findings suggest that combination therapy with nivolumab and ipilimumab may be unnecessary in many patient populations and that nivolumab alone may deliver equivalent clinical outcomes with lower toxicity (clinical and financial) in many advanced cancers other than melanoma,” the authors concluded.


The study, led by Anthony Serritella, MD, of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, was published August 31 in JAMA Oncology.


It’s possible that certain immunogenic nonmelanoma cancers or specific subsets of populations may have survival benefit with the combination over single-agent nivolumab, but it remains to be determined.


No funding source was reported, and the investigators report no relevant financial relationships.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected].

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  • Posted on September 18, 2023