Retifanlimab Approval Sets New Standard of Care in Advanced Anal Cancer: Sheela Rao, MBBS, MD, FRCP

On May 15, the FDA approved retifanlimab-dlwr (Zynyz; Incyte) in combination with platinum-based chemotherapy for the first-line treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal. It was also approved as a monotherapy for those whose disease has progressed or who are intolerant to platinum-based chemotherapy.

The approval was supported by data from the phase 3 POD1UM-303/InterAACT2 trial (NCT04472429) and the phase 2 POD1UM-202 trial (NCT03597295), establishing retifanlimab as the first and only FDA-approved first-line treatment for advanced anal cancer.

In an interview with The American Journal of Managed Care®, Sheela Rao, MBBS, MD, FRCP, consultant medical oncologist at The Royal Marsden Hospital and lead investigator of the POD1UM-303/InterAACT 2 trial, discusses the anticipated impact of this approval on clinical practice and the importance of ensuring equitable access. Looking ahead, she also shares key unanswered questions in anal cancer research and outlines directions for future trials.

This transcript was lightly edited; captions were auto-generated.

Transcript

As the first and only FDA-approved first-line treatment for advanced anal cancer, how do you anticipate retifanlimab will impact clinical practice and treatment decision-making?

Obviously, we're very excited about the FDA approval, and I do believe that this is a practice-changing regimen. I would hope that we would be able to deliver this to all patients who meet the eligibility, so any patient in the advanced setting should now be able to receive this combination.

I've just come back from a meeting at ASCO [the American Society of Clinical Oncology Annual Meeting], where we've discussed this broadly with many oncologists. Certainly, once this licensing, we're awaiting, obviously, European licensing and UK subsequently, but certainly for now, within the US, I would say this is on the NCCN [National Comprehensive Cancer Network] guidelines. Obviously, after this approval, the recommendation will be on the NCCN guidelines.

What challenges, if any, do you foresee in ensuring equitable access to retifanlimab, especially in underserved settings?

That's a good question, and something we also addressed at a meeting recently. Some of this, it's about education. It's about patient and physician education, and also ensuring that, if it's not feasible at one center, that there's a hub or another center [where] this can be given.

This is something we're working strongly with oncologists, and something we discussed at a meeting just recently. I would strongly encourage oncologists to reach out to other centers if they believe that they're not able to give it.

Having said that, it is a very straightforward regimen. Therefore, I would hope it should be able to be delivered everywhere. In terms of underserved populations, or in terms of costs, again, this is something that the company [Incyte] is working quite strongly [on], after the FDA approval.

I would hope that, eventually, this is something that should be able to be delivered quite easily in the community center, as well as in the bigger centers. That's certainly what I was led to believe from our recent meetings.

Looking ahead, what are the most pressing unanswered questions in anal cancer research? Are there any ongoing or upcoming clinical trials you're particularly excited about?

In terms of unmet needs, there's still quite a lot of unmet needs in anal cancer. It's a cancer that, particularly, in the advanced setting, there has been less research [on it] until recently. Obviously, these phase 3 data are really encouraging. Things that we're still answering, even from this trial, that will be important to look at are further translational work and biomarker work to understand if there are particularly exceptional groups.

I think the things to note in this trial were that, actually, the CPS [Combined Positive Score] score of greater than 1 applied to most patients, more than 90% in both arms. There is not a need to correlate that in terms of giving the treatment. We also included patients with metastatic liver disease, and they also seem to get equally good responses. Again, that's not a group that we need to exclude.

But going forward, in terms of unanswered questions, we need to understand what happens next when they do get resistance to the immunotherapy, what we give after that, and that's the subject of further research. We need to understand the biology of what's happening there. We need to understand whether patients, beyond this treatment, what are the next lines of treatment? What is the biology that drives those next lines of treatment?

In terms of in the earlier setting, there are no trials currently with retafanlimab in the earlier setting, but there are trials being planned, etc. It's an area that, clearly, the next steps are potentially to explore whether there is any role for immunotherapy earlier on in the locoregional setting. Those are trials that are in planning.

In terms of the locoregional settings, there's also, obviously, a lot of different questions in anal cancer in that group about how to improve the treatment, how to make sure that the side effects are better, how to ensure the quality of life is better in the early setting, and how to, again, identify patients who may not respond as well to locoregional treatment, who may need more enhanced treatment.

There's a lot of different questions, some around the treatment, some around the biology, but plenty to still explore.