New and Investigational Approaches to Anal Carcinoma Treatment

Charles J. Schneider, MD, FACP

The treatment of patients with early disease anal carcinoma has not changed much from the 1980s due to the fact that chemotherapy and radiation has continued to show high cure rates in this patient population.

Between 1990 and 2010, both incidence and mortality of the rare malignancy have increased, underscoring the need for more therapies. According to Charles J. Schneider, MD, FACP, who spoke about the subject in an interview with Targeted Oncology™, the incidence of occurrence has increased by about 2.7% per year with an increasing mortality in the space at roughly 3.1% year after year.

Schneider also explained that a preventative strategy for patients with anal carcinoma is the human papillomavirus (HPV) vaccination. As more children aged 12 years and older are vaccinated, a potential for decreased rates of this cancer and mortality rate occur.

Additionally, immunotherapy and targeted therapy has come front and center for treating patients with anal carcinoma with the advancements of nivolumab (Opdivo) and pembrolizumab (Keytruda). These 2 PD-1 inhibitors have become the standard of care for patients with advanced disease who are resistant to chemotherapy in advanced disease

During the interview, Schneider, a clinical professor of Medicine at the Abramson Cancer Center at Perelman Center for Advanced Medicine, provided an overview of the treatment landscape for anal carcinoma, and ongoing research.

What did you discuss at the NCCN 2022 Annual Conference regarding new approaches for the treatment of patients with anal cell carcinoma?

I was a co-presenter with Cathy Eng ,MD, FACP, FASCO, and I gave the first portion of the presentation, which was split into 2 parts.

The first part was focused on the tumor and immune environment, which is pretty unique in anal cancer. It is mostly driven by the HPV and facilitated to some extent by the human immunodeficiency virus [HIV] in patients who are HIV positive. A lot of that first part was focused on how these viruses facilitated in causing cancer.

Then the second half was a very comprehensive review, historically, of all the important trials that have led us to standard of care, both in localized disease and advanced disease. After that, Eng gave an update on current clinical trials.

What does the current landscape look like for this patient population?

The incidence and mortality is rather low, but despite the cancer being a rare malignancy, both incidence and mortality has been increasing between 1990 up until about the year 2010 with incidents increasing by about 2.7% per year and mortality by about 3.1% per year.

Hopefully, the HPV vaccination in children ages 12 and older will eventually lead to a plateau of that rising incidence and mortality and hopefully a decrease, but that's going to take a while since the HPV effect takes years on the canal.

In what ways has the management and care of these patients changed over the past decade?

Our treatment for early disease, and this sounds kind of horrible, but it really has not changed much at all since the 1980s. The reason is because nothing has been found to be better than the chemotherapy and radiation that we use for early-stage disease with very high cure rates. The only thing new really and local disease, I'd say two things. The first is that more patients are being treated now with an oral chemotherapy drug as a substitute for 1 of the 2 [intravenous] drugs with radiation with comparable cure rates. Then the second is that we are investigating immunotherapy as a component of treatment for localized disease as well, for advanced disease.

Immunotherapy and targeted therapy has come to the forefront. You know, especially with the PD-1 inhibitors of a drug called nivolumab (Opdivo) and a drug called pembrolizumab (Keytruda), which had become our standard of care for patients who were resistant to chemotherapy in advanced disease.

What unmet needs still need to be filled in this space?

The first thing is, although it sounds counterintuitive, patients who are not infected with HPV, [HPV-negative] and have anal cancer that's not induced by that virus have a much worse prognosis. We need to make advances in that patient population. About 80% of anal cancers are caused by high-risk HPV infection, either HPV16 or HPV18. The other 20% are not induced by HPV and those patients have a much worse prognosis. That's the first group.

Then in the second group, the incidence is much higher in African American men and that may have to do with lack of surveillance or other factors that need to be addressed. Other risk groups such as cigarette smokers, and immunosuppressed patients, especially organ transplant patients, and also women with either cervical dysplasia or cervical cancer, both of those are related to HPV. We need to do a better job in identifying those high-risk groups and using public health interventions in efforts to step that up in those populations.

Is there any ongoing research currently examining patients with anal cell carcinoma?

We have a lot of research ongoing. For instance, we just completed accruing nationally to a trial through the Eastern Cooperative Oncology Group that assigned patients after receiving potentially curative and intensive chemotherapy radiation for early disease, assigning them to either observation, which is our standard of care vs 6 months of immunotherapy using the drug nivolumab. That's an exciting trial that's been completed, and we're just waiting for results. We are hoping that adding immunotherapy to the treatment paradigm for early-stage disease will improve survival in that group even higher.

Second is localized disease. There's an ongoing trial that's looking at lowering the amount of radiation given which would reduce toxicity from radiation to the area to the pelvis, while still hopefully maintaining high cure rates. In advanced disease, there are many trials that are looking at different immunotherapy drugs, and also adding immunotherapy to chemotherapy, which would be the logical next step.

What does the future look like for the space?

I think the future is going to hinge on immunotherapy bench research and research on targeted drugs that may change the immune environment in anal cancer or specifically target anal cancer cells. I think the future looks bright in a cancer that's rare but still increasing in incidence and mortality. It is important that we make further advances.

The only thing I would say to patients and families is to please participate in trials because that's really the only avenue that we have to improve standard of care and improve survival of anal cancer and any other cancer.