Earle Burgess: Analysis of the just published EV-302 study

Earle Burgess, Genitourinary Medical Oncologist, Atrium Health Levine Cancer Institute, shared a post by LinkedIn:

“Is use of enfortumab (Ev) and pembrolizumab (Pem) the new standard for advanced urothelial bladder cancer? Analysis of the just published EV-302 study:

In the trial, initial treatment with the combination of Ev + Pem was found to be better than the old standard with chemotherapy in patients with advanced urothelial cancer (aUC).

But are the Ev + Pem results seen in EV-302 likely to be as good in the real world?

Let’s dig into the trial details to find out…

But first, some important context about what is the standard of care for this patient population in the US.

Prior to the EV-302 study, the standard for most US patients with aUC was to receive the following sequence of treatments:
1. Platinum doublet chemotherapy (gemcitabine + cisplatin or carboplatin)
2. Maintenance immune checkpoint inhibitor (ICI) with avelumab if no cancer growth on #1 OR treatment with an ICI (like pembrolizumab) at the time of cancer growth
3. Enfortumab monotherapy at the time of cancer growth after 1+2 above.

In the EV-302 trial, patients with aUC were randomized to receive either A) Ev + Pem (experimental arm) or B) platinum doublet chemotherapy (control arm = “standard of care”)

What were the findings?

Ev + Pem improved progression free survival: 12.5 months compared to 6.3 months with chemotherapy.
Ev + Pem improved overall survival (OS): 31.5 months compared to 16.1 months with chemotherapy.

Looks very good….IF most of the patients in the control arm received an ICI and Ev after front line chemo.

So what treatments did the control arm patients receive after chemotherapy?
313/444 (70.5%) received any treatment. (seems a little low to me)
260/444 (58.6%) received an ICI (seems too low to me. should be higher.)
?/444 (? %) received enfortumab. We don’t know. This information wasn’t provided, which obfuscates our ability to interpret the OS results.

So, in the EV-302 control arm, only 59% received an ICI, and unknown % (assume low since it wasn’t reported) received Ev.

Thus a significant percent of patients on the control arm did not receive the US standard of care after completing chemotherapy.

Can we say using Ev + Pem in the front-line setting is truly better than the “standard of care” in the US based on the EV-302 results?

Unfortunately, no. It might be, but it might not be since the trial design didn’t ensure adequate post-protocol therapy.

What would have been a better design for EV-302?

Randomize patients to receive Ev + Pem followed by chemo at progression vs. chemo followed by Ev + Pem at progression.

If front-line Ev + Pem were better in that hypothetical trial, I’d be all in on using the combo up front.

Instead, the EV-302 trial results leave us with an incomplete data set and confusion on how best to apply to our patients.”

Source: Earle Burgess/LinkedIn