Clinical Trials in Treatments for Anal Cancer

At the 2023 Great Debates and Updates in Gastrointestinal Malignancies meeting, Cathy Eng, MD, Vanderbilt-Ingram Cancer Center, Nashville, TN, offered her perspectives on the current and upcoming clinical trials for treatments of anal cancer.

Dr Eng reviews the currently ongoing and open-to-enrollment clinical trials looking into different treatments for anal cancer, stressing the importance of education and awareness of this particular cancer.

Transcript:

Hi, I'm Dr. Cathy Eng from Vanderbilt-Ingram Cancer Center in Nashville, Tennessee. I'm the co-director of the GI program and I'm the director of the Young Adult Cancers Program as well. We are at Great Debates and Updates in Gastrointestinal Malignancies here in Chicago.

The talk I gave earlier in the week was about the clinical trial development in anal carcinoma, and it was really focused on bringing increased education awareness to the fact that anal carcinoma, and I'm referring specifically to squamous cell carcinoma, is rising in incidence by about 2.7% per year and has been rising for over a decade. And it impacts about a little less than 10,000 individuals. The majority of patients will present with earlier stage disease, meaning that it hasn't metastasized, where the standard of care would be combined chemoradiation therapy to cure the patients of their cancer and to hopefully avoid a surgical resection because surgery unfortunately would result in a permanent colostomy due to the location of the tumor.

I wanted people to understand that there's an ongoing trial. That's a national study being led by Dr Jennifer Dorth [Case Comprehensive Cancer Center at Case Western Reserve University] where I'm glad to say I'm a national co-PI on EA2182. It's specifically for earlier stage, so T1, T2, N0, non-metastatic squamous cell carcinoma, where we're looking at the role of reducing the dose of radiation therapy and hopefully reducing the toxicities associated with treatment. And so that's called the DECREASE trial.

For our metastatic patients, I wanted people to remember that there are a fair number of patients that are at high risk of recurrent disease despite having chemoradiation therapy for earlier stage tumors. Tumors that are greater than 4 centimeters, any node positivity, those are patients that are at high risk of progressing despite receiving chemoradiation therapy for curative intent or developing recurrent disease. And in those patients, unfortunately unless it's localized, they'll have metastatic disease. In that setting we have fewer options. Currently we have 2 phase 3 trials. One is ongoing outside the US for the most part involving the drug retifanlimab and that is being run by my colleague Sheila Rao [The Royal Marsden Hospital] in the UK.

It's a 1-to-1 randomization to carboplatin and weekly paclitaxel plus nivolumab. And then that will enroll about 300 patients. If you have a treatment-naïve patient and you are overseas, please consider enrolling to that clinical trial here in the United States.

We actually have the trial that I'm leading, which is EA2176. It's supported by ECOG, the Farrah Fawcett Foundation, the NCI, which is a 2-to-1 randomization enrolling hopefully up to 200 patients, also looking at carboplatin and weekly paclitaxel plus or minus nivolumab. And the primary endpoint here is progression-free survival. We're encouraging people, please, if you have a newly diagnosed metastatic patient, the majority of these patients do tend to present with diffuse metastatic disease, and we want to encourage you to try to enroll to these clinical trials. The chemotherapy arms by itself usually results in response rates, based upon our prior data from the InterAACT trial or EA2133, as high as 57% to 59%. We hope the addition of immunotherapy will add to the overall response, but also will improve the progression-free survival for our patients. And both trials do allow, once you complete at least 6 months of your chemotherapy, they both allow continuation of the immunotherapy for up to 2 years.

We’re really trying to make a difference. We hope these 2 trials will change the treatment paradigm for our metastatic patients. I know it's rather taboo for some people to discuss anal carcinoma and that is a big issue, but we want people to be aware. We want people to not just immediately get started on therapy without looking at the clinical trial options. And we want to encourage young investigators and junior faculty members to think about next steps for replacing some of these trials.

I also to mention, I think it's really important, there are 2 trials that have completed enrollment. One is specifically for the higher risk patient population; that after they completed their chemoradiation therapy, they were randomized to 6 months of immunotherapy in the adjuvant setting. That's EA2165, and we don't have those results yet. I'm looking forward to those results. And in full disclosure, I am a co-PI in that trial as well.

And then we finished enrollment to our trial, which is NCI9673 in the refractory setting, looking not only at single-agent immunotherapy, already approved in the setting, but also looking at the role of combined immunotherapy in the previously-treated metastatic patient population. And is that better than single agent immunotherapy? So is 2 better than 1 for our refractory patient population.

Those are the trials. I think that that's the current landscape, but we want to encourage pharmaceutical companies to really think about looking at this patient population. Ninety percent and more of these patients have HPV-associated anal carcinoma and any breakthroughs we can make for this cancer can impact the other HPV-associated cancers. And although it's less than 10,000 patients in the United States that are diagnosed with anal carcinoma, it's about 25,000 to 27,000 individuals globally are impacted by anal carcinoma. We really need to make better breakthroughs and we want pharmaceutical companies big and small to be supportive of this virally driven disease. Thank you so much.

Source:

Eng C. “Perspectives on Clinical Trial Development in Anal Cancer.” Presented at the Great Debates and Updates in Gastrointestinal Malignancies; March 30-April 1, 2023; Chicago, IL.