Ipilimumab Added to Nivolumab Does Not Significantly Improve Survival Outcomes for Patients With Squamous Cell Carcinoma of the Anal Canal

At the 2023 World Congress on Gastrointestinal Cancers, Van Morris, MD, MD Anderson Cancer Center at The University of Texas, Houston, Texas, presented on the phase 2 study evaluating combination nivolumab both alone and in combination with ipilimumab for the treatment of patients with previously treated, unresectable, or metastatic squamous cell carcinoma of the anal canal.

Dr Morris explained, "Overall, what we saw was the toxicity was greater with the nivolumab-ipilimumab combination, and although there were no statistically significant improvements in survival outcomes, there were trends toward improved benefit in patients who received the nivolumab-ipilimumab arm." 

Transcript:

Hi, my name is Van Morris and I'm an associate professor in the Department of Gastrointestinal Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston, Texas. And I'm really excited to be at the 2023 World Congress ON GI Cancers this year to present on behalf of our study team the results of the NCI9673 trial, which was a randomized phase 2 trial looking at nivolumab with or without ipilimumab in patients with treatment refractory unresectable or metastatic anal cancer.

We know that anal cancer is a rare population, but it is one in which the incidences is increasing annually, and more and more patients at the time of their initial presentation are being diagnosed with incurable metastatic disease. There's a really a huge unmet need to find new and effective therapies for this patient population.

Years ago, we had reported results from the first trial of immunotherapy in patients with treatment refractory, metastatic anal cancer. That was the NCI9673 trial part A, where we looked at nivolumab as a single agent. And what we reported was that the response rate was around 24%, and the median progression-free survival in that study was around 4 months.

To build upon this, we've recently completed the part B of this study, which was the randomized trial looking at nivolumab with or without the anti-CTLA4 antibody ipilimumab. Patients who had had prior treatment for their unresectable or metastatic anal cancer were eligible. Nobody was allowed to have had prior immunotherapy, and patients who were living with HIV were allowed to participate in this study, provided that they had a CD4 count greater than 250, an undetectable viral load, and were being followed by an infectious disease specialist.There were 100 participants randomized in a 1-to-1 fashion to nivolumab as monotherapy or to the combination of nivolumab with ipilimumab. The primary end point was progression-free survival (PFS), and secondary end points included overall survival, radiographic response, and safety and toxicity profiles.

We saw that there was a trend towards improved PFS: 3.7 months with the nivolumab-ipilimumab combination versus 2.9 months median progression-free survival with nivolumab as a single agent in our trial. This did not hit statistical significance, but we did see that in both arms there were patients who had durable responses.

The 6-month PFS rate for nivolumab with ipilimumab was 30%, whereas the 6-month PFS rate for nivolumab alone was 20%. Overall response rate was 21.5% with nivolumab plus ipilimumab versus 17% with nivolumab alone. And the overall disease control rate in both arms was right around 45%. Median overall survival was around 20 months for patients with the nivolumab-ipilimumab combination, whereas for nivolumab alone in Part B of this study, we observed and estimated the median PFS to be around 15 months.

As we've seen with other trials, which have looked at PD-1/CTLA4 combinations, the toxicity was greater in the combination arm. And in fact, there was 1 patient who experienced a grade 5 pneumonitis event on the nivolumab-ipilimumab combination. Grade 4 events were observed only in the combination group as well, and these included hyperglycemic episodes as well as treatment-related diabetic acidosis.

Overall, what we saw was the toxicity was greater with the nivolumab-ipilimumab combination, and although there were no statistically significant improvements in survival outcomes, there were trends toward improved benefit in patients who received the nivolumab-ipilimumab arm. I don't think that the results of our trial imply that we should, at this point, be moving to nivolumab-ipilimumab as a standard of care treatment for this patient population, but we do have ongoing biomarker studies looking at patterns of response to both nivolumab alone and the nivolumab-ipilimumab combination to understand better what may be preferentially driving durable treatment benefit in patients with refractory and metastatic anal cancer who are receiving immunotherapy. And we look forward to presenting those at a later congress.

Source:

Morris V, Ciombor K, Polite B, et al. NCI9673 (Part B): A multi-institutional ETCTN randomized phase II study of nivolumab with or without ipilimumab in refractory, metastatic squamous cell carcinoma of the anal canal. Presented at World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain. Abstract O-12