Post Conference Perspective: Immune Checkpoint Inhibitors in Advanced and Metastatic Urothelial Carcinoma - Episode 4

Role of Chemoimmunotherapy in Frontline Treatment of mUC

Petros Grivas, MD, PhD, discusses the role of concurrent immune checkpoint inhibition plus chemotherapy in first-line metastatic urothelial carcinoma and comments on the ongoing phase 3 NILE, CheckMate 901, and EV-3O2 studies.

Petros Grivas, MD, PhD: What is the role of concurrent chemoimmunotherapy, concurrent chemotherapy plus immunotherapy, in the frontline setting for advanced endothelial cancer? So far the data from the IMvigor130 and KEYNOTE-361 have not shown a significant overall survival benefit with a concurrent administration of chemotherapy and checkpoint inhibitors. This is interesting—I do not think we know the answer as to why this happens or what the reason for that is. There might be some discussion about the overlapping potential biomarkers, the underlying benefit from chemotherapy and immunotherapy. When you add them together, you may not add too much, because the same patients may respond to 1 more than the other. However, we know that, when it comes to the response rates with chemotherapy, it is higher when compared with immunotherapy alone, and it sounds like the sequential approach—chemotherapy first, followed by checkpoint inhibitor avelumab—

in the case of JAVELIN Bladder 100 trial prolongs overall survival, while the concurrent chemoimmunotherapy combination does not significantly prolong overall survival.

We have a couple of trials that are still ongoing. For example, the CheckMate901 trial, with nivolumab plus ipilimumab vs chemotherapy, also has a randomization of gemcitabine-cisplatin and nivolumab vs just gemcitabine-cisplatin, is going to answer this question. We are also going to see a longer follow-up from the IMvigor130, and we also have the NILE trial. The NILE trial is another important phase 3 study in this setting. It has 3 arms: 1 is chemotherapy alone, gemcitabine-cisplatin or gemcitabine-carboplatin, vs chemotherapy plus durvalumab anti-PD1 agent, and also chemotherapy plus durvalumab plus tremelimumab. So it’s a quadruple regimen, with chemotherapy plus doubled immunotherapy; this will be an important trial to keep an eye on. The trial is ongoing and called NILE, and we are going to see what the results are from that as well as from CheckMate901 and another trial in the frontline setting called EV-302. This compares enfortumab vedotin, an antibody-drug conjugate, plus pembrolizumab anti-PD1 with platinum-based chemotherapy.

Transcript edited for clarity.