Immunotherapy combination does not improve outcomes for patients with advanced anal cancer

MD Anderson Research News January 07, 2026

• Phase II ETCTN trial found ipilimumab plus nivolumab did not improve outcomes over nivolumab alone in patients with previously treated metastatic anal cancer
• The combination treatment caused more severe side effects than monotherapy
• Five-year survival for metastatic anal cancer remains below 40%, emphasizing the urgent need for effective treatments
• Study provides valuable insights for clinicians working to improve outcomes for patients with this rare malignancy

A multicenter Phase II study led by researchers at The University of Texas MD Anderson Cancer Center found that combining the immunotherapies ipilimumab and nivolumab did not improve outcomes over nivolumab alone for patients with refractory metastatic squamous cell carcinoma of the anal canal. 

The study, published in the Journal of Clinical Oncology, builds on earlier findings from the NCI9673 (Part A) trial, also led at MD Anderson, which established nivolumab as an active immunotherapy option for this difficult-to-treat patient population. This cohort evaluated whether dual checkpoint blockade therapy could further enhance anti-tumor activity. These results provide valuable insights as clinicians seek to improve outcomes while avoiding unnecessary treatments with added side effects.

“With 100 patients enrolled, this study represents one of the most comprehensive efforts to rigorously evaluate immunotherapy in metastatic anal cancer,” said principal investigator Van Morris, M.D., associate professor of Gastrointestinal Medical Oncology. “Checkpoint inhibition remains a promising therapy, and our findings show we must continue to pursue new strategies.”   

What are the results of adding ipilimumab to nivolumab on this trial?
The NCI9673 (Part B) trial enrolled 100 patients with refractory metastatic anal cancer, making it one of the largest prospective immunotherapy trials conducted in this rare cancer. Patients were assigned to receive either the anti-PD-1 antibody nivolumab or a combination of nivolumab and the anti-CTLA-4 antibody ipilimumab. Researchers evaluated the efficacy, safety and immune-modulating effects of the two regimens.

The study found that adding ipilimumab to nivolumab did not improve outcomes. Median progression-free survival was similar between the two treatment groups – 2.9 months with the combination compared to 3.0 months with nivolumab alone. Response rates also were similar, with 24% of patients responding to dual regimen therapy and 19% responding to monotherapy. More importantly, overall survival did not improve with the addition of ipilimumab.

The combination also had a higher burden of toxicity, with 25% of patients experiencing serious treatment-related side effects compared with 12% in the nivolumab-only cohort. 

Why is metastatic anal cancer so hard to study and treat?
Metastatic anal cancer is a rare disease, which creates significant challenges for advancing treatment. Although the disease is uncommon, rates of advanced cases have been increasing, and the limited treatment options highlight the urgent need for new therapies.

Immune checkpoint inhibitors have emerged as an important treatment option, but the current findings reinforce that combination strategies must be carefully evaluated to avoid added toxicity without clear benefits. Ongoing research continues to identify immune-based strategies to improve outcomes for patients with advanced human papillomavirus (HPV)-associated malignancies like anal cancer.

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Funding was provided by the National Institutes of Health/National Cancer Institute (UM1CA186689, P30CA068485, CA016672), MD Anderson institutional funding, the Farrah Fawcett Foundation, and an anonymous philanthropic donor. A full list of collaborating authors and their disclosures can be found with the paper.