Physicians Discuss Sequencing of Sacituzumab Govitecan in Bladder Cancer

Pedro C. Barata, MD, MSc

Assistant Professor of Medicine

Section of Hematology and Medical Oncology

Tulane University

New Orleans, LA

DISCUSSION QUESTIONS

• Have you had experience with sacituzumab govitecan (Trodelvy) in urothelial cancer? ​
• For which patients are you using it? ​
• How are you sequencing it with other lines of therapy in bladder cancer?​

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PEDRO C. BARATA, MD, MSc: Have you used sacituzumab govitecan? How do you see the data that supported accelerated approval of the compound?

WAIL ALNAS, MD: I have not used it in bladder cancer. I use it a lot in breast cancer so I’m very familiar with it. Initially, it was a learning curve; the neutropenia and the diarrhea were a little bit surprising when we are using an antibody-drug conjugate, but we learned how to take it more seriously. With growth factors routinely [used], it’s very well tolerated.

I have a younger patient who failed chemotherapy, then failed immunotherapy, so we added enfortumab vedotin [EV; Padcev] but we continued the immunotherapy. I don’t know if that’s legitimate or completely off the books here.

BARATA: That’s a great question. We do certainly lack data to show a benefit of EV/pembrolizumab [Keytruda] post immunotherapy. We don’t have that data. The data are not clear. That doesn’t mean it might not work to, when you progress on pembrolizumab, add EV. I think we’re figuring out the synergistic effect.

By the way, your experience with sacituzumab in breast cancer, to your point, you think it’s manageable, especially if you do G-CSF [granulocyte colony-stimulating factor].

ALNAS:Oh, absolutely. Nowadays, it’s a very well-tolerated agent. We have learned how to use it.

IRA SUROLIA, MD: I have not used sacituzumab yet.

BARATA: Not in any cancer, correct?

SUROLIA: No. But I believe that sacituzumab will be efficacious and I like its AE profile a little better than that of EV. I also know that sacituzumab is effective across a lot of cancers, [and is in] phase 2 trials right now, including small cell lung cancer [NCT05633667]. I am happy to use it once we get to the third line. I have a few patients that start [treatment for metastatic urothelial cancer] and most of them don’t make it beyond the second line.

BARATA: Based on the data that you’ve seen, it sounds to me that the data were enough to impress you. Is that a situation where you’re going to be thinking EV or sacituzumab?

SUROLIA: I wanted to ask you earlier: There was a significant fatality rate on the phase 2 trial with EV.¹ Do you know if that got better in the phase 3 trial?

BARATA: I cannot recall the number of deaths on the phase 3 trial…. That’s certainly a learning curve with EV. It’s not a walk in the park for some patients. What I can tell that from the efficacy perspective is I’ve seen patients that EV didn’t touch the disease and sacituzumab was able to control it, which is quite interesting.

I don’t know if others have that experience or not, but they’re definitely different compounds and it’s interesting to see. I don’t know if that has to do with the expression of Trop-2 or Nectin-4 because we don’t [test for] it in clinical practice. But that is the experience I have with it and I’ve used it, so I agree with you that the data, to me at least, was compelling to offer it to patients for sure. I do it routinely—let me put it that way.

DISCUSSION QUESTIONS

• How should neutropenia be monitored/managed?​
• What about diarrhea associated with sacituzumab govitecan?​
• How do you/should you counsel patients regarding potential toxicities with this agent?​

BARATA: Dr Nidhiry, have you used sacituzumab? If so, neutropenia can occur and in addition to that, you can see some diarrhea.² What do you do for that, if you’ve used it?

EMMANUEL NIDHIRY, MD: I’ve used it in 1 patient after the progression on EV, and the neutropenia was a major issue for that patient. Diarrhea wasn’t as much of a problem. I used diphenoxylate/atropine [Lomotil] to manage the diarrhea and it seemed to work.

BARATA: Did [sacituzumab] work for your patient?

NIDHIRY: The patient seemed to benefit for a few months and then he progressed, but he got a few months out of it.

BARATA: Since you’ve used it, how did you counsel the patient regarding what you might expect with the profile of sacituzumab?

NIDHIRY: I told them this is [like] some of the chemotherapy-based treatments and he could experience AEs similar to chemotherapy, including risk of infections and diarrhea, and we discussed that. He was already through EV and EV is a similar drug, not with the same AEs but it’s an antibody-drug conjugate, so he was familiar. He was open to trying it. His performance status was still pretty good, and he was open to keep going, and that is why I decided to pursue this.

MOHAMAD KHASAWNEH, MD: I did use both agents in urothelial cancer. I also used sacituzumab in the breast cancer population. The skin toxicity for EV is definitely there, I’ve seen it, and I typically counsel the patient about that. With sacituzumab, myelosuppression and fatigue are very noticeable.

But we always counsel the patients that unfortunately, when urothelial cancer comes back, there are 2 points I like to stress. One, this is an incurable cancer. The second thing is that if they get to second line, there is a good chance they will not get to a third-line setting because the percentage of patients who can move from 1 line to the other drops with subsequent lines of therapy. You might want to use your most efficacious drugs up front because the chance of them being able to receive subsequent line of therapy dwindles down the line.

There is skin toxicity with EV, but I think the recent approval of EV with pembrolizumab³ will make us use that combination more up front because of the amazing 70% objective response rates that we’ve seen in the phase 2 data,⁴ and I hope to see this pans out in the phase 3 study and translates into overall survival benefit.

BARATA: So you consider the antibody-drug conjugates very active options. Do you think they’re both better than the platinum-based chemotherapy? Is that something you will see in the future doing EV and sacituzumab for a patient who has not received a platinum-containing regimen, for example?

KHASAWNEH: Yes, I started using that a few months ago, even before the FDA accelerated approval [of EV plus pembrolizumab].

_References:

_{1. Yu EY, Petrylak DP, O'Donnell PH, et al. Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV‑201): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2021;22(6):872-882. doi:10.1016/S1470-2045(21)00094-2}

_{2. Tagawa ST, Balar AV, Petrylak DP, et al. TROPHY-U-01: a phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors. J Clin Oncol. 2021;39(22):2474-2485. doi:10.1200/JCO.20.03489}

_{3. FDA grants accelerated approval to enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial carcinoma. News release FDA. April 3, 2023. Accessed June 14, 2023. https://bit.ly/4062b7b}

_{4. Hoimes CJ, Flaig TW, Milowsky MI, et al. Enfortumab vedotin plus pembrolizumab in previously untreated advanced urothelial cancer. J Clin Oncol. 2023;41(1):22-31. doi:10.1200/JCO.22.01643}