Emerging Data From ASCO GU 2021 in Urothelial Carcinoma

Petros Grivas, MD, PhD, discusses exciting findings and impactful data from the 2021 ASCO GU Virtual Symposium for the treatment of urothelial carcinoma.

Petros Grivas, MD, PhD: The ASCO GU [American Society of Clinical Oncology Genitourinary Cancers Symposium] 2021 was a great meeting. There were multiple important data sets. What are the most important data sets? It is hard to answer this in a couple of minutes, but there were some interesting biomarker and genomics data in the nonmuscle invasive disease setting, discussions about nonmuscle invasive diseases, and choices of therapy. In response to muscle-invasive bladder cancer, I recommend the audience look at that nice session. There were a couple of interesting phase 2 trials looking at chemotherapy and immunotherapy in the neoadjuvant setting. They are not practice changing but definitely interesting to review.

One of the biggest data sets was from Dr [Dean] Bajorin, who worked on the adjuvant CheckMate 274 trial, which was very important. It was probably 1 of the most important trials discussed in this meeting. It examined adjuvant nivolumab vs placebo in patients with resected urothelial cancer, bladder cancer, or upper-tract urothelial cancer. About 21% of patients had an upper-tract disease. Patients in the trial were randomized to nivolumab vs placebos, and adjuvant nivolumab significantly prolonged disease-free survival in all patients, in the intent-to-treat population but also in a subset of patients with PD-L1-high tumors. The hazard ratio was 0.70 in all comers and 0.53 for patients with PD-L1–high tumors. So there was a dramatic difference in disease-free survival [DFS]. This is a very significant discussion and debate in the scientific community, and among urothelial cancer experts. Is that enough to change practice? Is the disease-free survival benefit dramatic enough to change practice and use adjuvant nivolumab in those patients, or should we wait for overall survival [OS] to improve? If the latter is the case, is DFS a surrogate for OS in the immunotherapy adjuvant setting? We do not know the answer to this question. It will be interesting to see how this pans out and what the regulatory agencies will say. Is DFS enough? Do we need to wait for OS? These are very important questions.

In metastatic disease, we saw many interesting presentations. One of the highlights was the data concerning enfortumab vedotin from the EV-201 phase 2 study, a single arm, cohort 2, [presented] by Dr [Arjun] Balar. It had an impressive 52% overall response rate with enfortumab vedotin in patients who never received platinum-based chemotherapy with an advanced disease. They progressed on checkpoint inhibitors, and they received enfortumab vedotin as second-line therapy. Fifty-two percent is a very impressive figure. Obviously we will have to look at toxicity and think about neuropathy, hyperglycemia, skin rash, and other AEs [adverse events] with enfortumab, but those are very impressive data. There were 89 patients, and we will have to see whether this will be considered for accelerated approval in the second-line space in patients who never got platinum.

One of the biggest takeaways was from the EV-301 trial, with Professor [Thomas] Powles presenting the data. EV, enfortumab vedotin, which is an antibody-drug conjugate, was compared with a taxane single agent, or vinflunine in Europe. It showed overall survival benefits and PFS [progression-free survival] at a high response rate, with enfortumab vedotin as a third-line therapy, or beyond, after platinum-based chemotherapy, after immune checkpoint inhibitors. For third-line therapy and beyond, enfortumab vedotin has level 1 evidence with significant overall survival and PFS benefits and a response rate of about 41% in heavily treated patients. Enfortumab vedotin has accelerated approval already by the FDA in this third-line space, but this is likely to result in a full regulatory approval. These are very important data, but it is important to look at toxicity.

We had some interesting trials and progress. For example, sacituzumab govitecan, the IMMU-132-01 trial drug, looks very promising. There’s a trial in progress, called TROPiCS-04, comparing sacituzumab govitecan with chemotherapy, which has a similar design to the EV-301 trial. The trial is ongoing. There are a few other studies looking at this. One is looking at the inhibiting PD-L1 TGF-beta in platinum-refractory disease, with a very interesting molecule called bintrafusp alfa. There was some other interesting data, and I encourage the audience to review them at the ASCO [American Society of Clinical Oncology] website.

Transcript edited for clarity.

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