POD1UM-303/InterAACT 2: Potentially Practice-Changing Findings in SCAC

Sheela Rao, MBBS, FRCP, MD, consultant medical oncologist in the Gastrointestinal Unit at the Royal Marsden Hospital in Sutton, Surrey, United Kingdom, discussed the findings of the POD1UM-303/InterAACT 2 trial of retifanlimab plus chemotherapy for inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC). The phase 3, double-blind, controlled trial met its primary end point, with improved median progression-free survival (PFS) in the chemotherapy plus retifanlimab arm vs chemotherapy plus placebo (9.30 months vs 7.39 months [HR, 0.63; 95% CI, 0.47-0.84]).

The new findings were presented during a presidential symposium highlighting potentially practice-changing data at the European Society for Medical Oncology Congress 2024.

Transcript

What were the main findings presented at ESMO 2024, and what do these results add to previous data on retifanlimab in SCAC?
The data from POD1UM-303 show an impressive and meaningful improvement in progression-free survival with the addition of retifanlimab to carboplatin and paclitaxel. We also see a trend toward improved overall survival, although those data are not yet fully mature, and we also see an improvement in response rate, duration of response, and disease control. In addition to that, it was very well tolerated, and there were no concerning safety signals in terms of the toxicity.

In summary, this now represents a new standard of care, potentially, in this disease, and there are very few trials in this disease, so this really does offer a new treatment option for our patients.

How does the PFS seen with retifanlimab plus chemotherapy in the study compare with currently available treatments for SCAC?

It's a good question. There's not many that have been tested in clinical trials, but obviously, carboplatin and paclitaxel, we tested in the InterAACT trial earlier. The median PFS there was 8 months, but that was a smaller study of about 90 patients. In this study, the PFS for the control group was 7 months. I think the key is here that one needs to be careful looking at the median value, because there is still improvement from 7 or 8 months to 9.3 months. But the point here is more to look at the hazard ratio, which is 0.63, which is quite meaningful.

Were there any significant differences in efficacy or safety among patient subgroups?

At this point in time, we don't have that data, but certainly on first look, there does not appear to be. We do note that the majority of patients in both arms had a combined positive score greater than 1, so over 90% in both arms. We are looking at other subgroups, and of note, at least a third of patients in both arms have metastatic disease in the liver. This did also not seem to influence efficacy, but obviously that's something we'll look at in more detail.

How does the safety profile of retifanlimab plus chemotherapy compare with chemotherapy alone?

There are slightly more side effects, as one would expect when one adds in retifanlimab. They were manageable. They were mainly immune-related side effects such as thyroid dysfunction, adrenal insufficiency, skin toxicity—all of which were manageable and did not really disrupt chemotherapy administration. So, as expected.

What implications could the results of this study have for future treatment guidelines for squamous cell anal carcinoma?

Well, we met the primary end point. I think we have shown meaningful and clinically meaningful improvements in efficacy, including progression-free survival and really promising survival trends. So, I would certainly hope that going forward—and this was a global study, by the way, as well—I really would hope that this would change practice globally for patients with advanced squamous cell cancer of the anus.

Can you speak to the importance of conducting international trials like this one in rare forms of cancer?

So, rare cancers are sometimes underserved by clinical trials because clearly it is difficult to do them. This trial involved 81 centers globally recruiting 300 patients, which clearly means that there are many centers recruiting small numbers of patients. And for rare cancers, this is the key. It's the only way to move forward and get some meaningful treatment options. We have to do strong international collaborations like this.

Reference

Rao S, Samalin-Scalzi E, Evesque L, et al. Phase 3 study of retifanlimab with carboplatin-paclitaxel (C-P) in patients (pts) with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) not previously treated with systemic chemotherapy (chemo). Presented at: European Society of Medical Oncology Congress 2024; September 13-17, 2024; Barcelona, Spain. Abstract LBA2.