A Treatment Plan for Advanced Urothelial Carcinoma With Spinal and Liver Metastasis

Benjamin Miron, MD, Fox Chase Cancer Center, Philadelphia, PA, discusses the course of treatment he would take for a patient with advanced urothelial carcinoma with a spinal lesion. Following first-line chemotherapy with dose-dense MVAC, palliative radiotherapy and switch maintenance therapy with avelumab, metastatic lesions are observed in the spine and liver during CT without contract.

Transcript:

Hi, my name is Ben Miron. I'm a medical oncologist at Fox Chase Cancer Center in Philadelphia, and I'm very excited to be here today to talk about a case of a patient with advanced urothelial cancer that highlights some of the important learning points about the management of this disease.

This case is of a relatively young woman who is aged 50 years and in very good health who was diagnosed with bladder cancer after seeing blood in her urine. She had a specialized CT scan to evaluate her urinary system called a CT urogram, which showed a 2.5 cm tumor in her bladder. She then saw a urologist who surgically removed the tumor from within the bladder using a cystoscopy in a procedure called TURBT. And the pathology from that showed a high-grade urothelial carcinoma with deep invasion into the muscle. She then had a new CT scan to complete her staging, and unfortunately that showed a lesion in the spine at the level of L1, which was confirmed on MRI and then biopsy to be consistent with metastatic disease.

When the patient saw medical oncology, she had very good performance status of ECOG 0, and she also had no significant past medical or surgical history, and her kidney function was very good with the GFR greater than 60. She also had comprehensive molecular profiling, which showed that PD-L1 was negative, TMV was 12, and the tumor was microsatellite stable. Of note, she also had no activating mutations in FGFR2 or FGFR3. In this setting for patients who are cisplatin-eligible based on the Galsky criteria, the standard of care is cisplatin-based chemotherapy regimens. And after a discussion of the risk-benefit with her, we decided to start dose-dense MVAC, which she received for 5 cycles.

She had a staging scan at the time of completing the 5 cycles which showed stable disease. And then we discussed with her the data from the JAVELIN-100-Bladder study published in the New England Journal of Medicine in 2020, which showed that maintenance therapy with the immune checkpoint inhibitor avelumab prolonged survival compared to best supportive care for patients who had disease control defined as stable disease or better by RECIST criteria after platinum-based chemotherapy.

She agreed to proceed with maintenance avelumab, which we gave 800 mg given every 2 weeks and prior to starting, because she had some discomfort in the area of her spinal metastases, she had some palliative radiation with that area. However, unfortunately, on the first restaging scan after 6 cycles of therapy, she had multiple new metastatic lesions in her liver and in her spine. At this point, her ECOG performance status was now 1, mostly due to pain in her back, and she had some tinnitus in her ears from prior treatment with cisplatin.

We discussed next steps at that point and the best evidence to support our decision. And in doing that, we talked about EV-301, which is a study again from the New England Journal of Medicine in 2021 this time comparing enfortumab vedotin versus investigator choice chemotherapy, which included docetaxel, paclitaxel, or vinflunine, mostly in Europe. And this is for patients who are already treated with platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor, which is the case for her. And EV-301 showed that enfortumab vedotin significantly prolonged survival compared to chemotherapy in the setting, and it had an acceptable toxicity profile. We felt like this is the best option for her, and she agreed. We started enfortumab vedotin based on the label, given at 1.25 mg/kg, 3 weeks on and 1 week off.

And she tolerated this treatment well. And on her first restaging scan, we were surprised to see that there was interval progression of multiple bone metastasis and a suboptimal evaluation of her liver metastasis due to a lack of IV contrast. In this situation, we probably would've used IV contrast, but at the time of this case, there was a national shortage of IV contrast in the United States, and this is something that many people had to deal with.

The question here is what would you do next? I want to go through the options in our quiz one by one. The first option is to change therapies to sacituzumab govitecan, which has an accelerated FDA approval based on phase 2 data in this setting from cohort 2 of the TROPY-U-01 trial, which was published in Journal of Clinical Oncology in 2019. This study showed that this drug has good activity in this setting with a response rate of 27% and an acceptable toxicity. And if there was unequivocal progression of disease, this would be a very good option at this point. But we have to consider what the scan result is really telling us. And what we see is that the CT report only really shows growth in bone metastasis, which can be tricky to evaluate. And liver lesions in this case were not well characterized. Given that finding, it's probably beneficial to get a more in-depth evaluation of the state of disease.

And we have a couple choices for that here. One of them is to send a ctDNA test, which would be an enticing option based on some of the available data with these tests that are designed to monitor for response. It's been shown that ctDNA in the blood/plasma correlates very well with disease activity. It's often seen to rise before progression is seen on scans, and it often goes down when patients are responding. However, given that we don't have a baseline result with ctDNA testing for this patient, we can't accurately calculate a dynamic change. It wouldn't be very useful in this case unless it was completely negative.

Our next option with regards to the disease evaluation is a PET scan, and that's what I would've chosen and did choose here, especially given the contrast shortage that existed at this time and the fact that the patient had lesions in multiple areas of the body, making multiple MRIs a little bit less practical. We know that PET CT is not perfect, but it does help us get an understanding of the metabolic activity of lesions, both in bone and in the liver. And that might help us understand if this is a true progression.

In this case, the patient had a PET CT, and it showed that none of the lesions that we saw on CT had any significant activity on the PET scan, suggesting that the patient was having an ongoing very good response to enfortumab vedotin. That was a good result for this patient, and we were very happy to see it.

Just for completeness, I want to discuss the last 2 choices we had in this quiz, which is treatment with erdafitinib, which I wouldn't suggest in this patient since there's no role for this agent in the absence of an activating FGFR2/3 mutation. And lastly, there's an option to re-challenge with platinum-based chemotherapy. Although there's no real randomized comparisons with sacituzumab govitecan in this disease setting, it's probably not the best choice because she was recently exposed to this type of regimen and didn't really achieve a deep response, only had stable disease after 5 cycles.

That's my summary of this case, and thank you very much for listening. I hope it was helpful in thinking about how you treat advanced urothelial cancer.