Emergent Data in Frontline and Maintenance Therapy for Metastatic Bladder Cancer


Dr Jain discusses latest data in frontline and maintenance therapy for metastatic bladder cancer and Mr. Ehas shares his experiences during the course of his treatment.


Rohit Jain, MD, MPH: Moving forward, I discussed…the chemotherapy with cisplatin, but there have been some more developments in the treatment options for patients now in metastatic urothelial carcinoma. And 1 of [those] combinations is enfortumab vedotin with pembrolizumab. Enfortumab is an antibody-drug conjugate, which has a payload of a microT inhibitor called as monomethyl auristatin E. And in a phase 3 trial in…patients who have received chemo[therapy] and immune therapy, it showed a response rate of [approximately] 40%. And now…enfortumab is being combined with pembro [pembrolizumab] in the phase 1B/2 trial, which was EV-103 [NCT03288545].

And recently there was a 4-year update, which showed that the objective response rate with the combination was [approximately] 73%, which is astonishingly high. And the median overall survival exceeding 2 years at 26 months and the tail of the curve was still holding strong. When we look at the median progression-free survival, it was 12.7 months with 16% complete responses. So, following that, EV-103 cohort K also showed similar results with a combination of enfortumab with pembrolizumab, with an objective response rate of 64%. These data actually have led to the combination approval by [the] FDA and it got an accelerated approval, and the patients are being treated who are cisplatin ineligible with a combination of enfortumab and pembrolizumab now.

So, when we spoke earlier, I discussed that Mr Ehas [received] chemotherapy and then went on having maintenance immune therapy. So, when we look at this treatment option, 3 decades ago, we were not doing that … Patients were getting platinum-based chemotherapy. We were maintaining them on observation, and they remained on observation as standard of care for at least 3 decades for patients with advanced metastatic urothelial carcinoma. And although the chemotherapy had a good response, which was [approximately] 40% and 50%, the response was not durable. And when we look at the progression-free survival, it was [approximately] 6 to 8 months, and the median overall survival was [approximately] 9 to 15 months only. And the maintenance therapy part, it has been studied and established in other tumor types such as lung, breast, ovarian, and other [gastrointestinal] cancers. In urothelial cancer, multiple trials were conducted using different drugs, such as sunitinib or PARP inhibitor, but they were not successful.

When we talk about the switch maintenance therapy, what it refers to basically, it’s a sequential treatment with a new agent but with a different mechanism of action, which is less toxic. And it is used to maintain that disease control after the fixed duration of the initial systemic therapy. So that is the foundation of the JAVELIN Bladder 100 trial [NCT02603432], which was a phase 3 trial, a multicenter international trial, which enrolled 700 patients with metastatic urothelial carcinoma. And the study compared maintenance avelumab plus basic supportive care with basic supportive care alone. These patients received 4 to 6 cycles of platinum-based chemotherapy, which is either cisplatin or carboplatin. And those who attained a stable disease, partial response, or complete response after the chemotherapy, they were allowed to go on the trial.

In the initial results, what we saw is after a follow-up of 19 months, avelumab maintenance significantly improved overall survival in the study population. The median overall survival was 21 months in the avelumab [arm] vs 14 months in the basic supportive care [arm]. And that overall survival was also significantly prolonged in the PD-L1—high population, where the median overall survival was not reached in the avelumab arm, but it was 17 months in the basic supportive care [arm]. Now, when we look at the long-term follow-up data of avelumab maintenance, we see that the overall survival benefit over basic supportive care has been maintained with the median follow-up of more than 38 months. The median overall survival measured from the start of the first-line chemo[therapy] reached 29.7 months with avelumab maintenance, which established a new benchmark for the first-line regimen in patients with metastatic urothelial carcinoma [who] did not progress after 4 to 6 cycles of the first-line chemotherapy. The avelumab conferred an overall survival advantage regardless of whether the patient received cisplatin or carboplatin-based chemotherapy as the initial treatment.

The safety profile was also acceptable during the treatment. When we look at the treatment-related adverse effects, around 78% of the patients developed that, but only 19% of the patient had grade 3 [adverse] effects, and most of the patient only had single immune-related treatment-associated adverse effects. So, moving toward the maintenance therapy, we finished 6 cycles of dosage and back, and then we started on avelumab. So, Jeffrey, what [adverse] effects did you experience while you were on avelumab as a maintenance therapy?

Jeffrey Ehas: The overall treatment went very well. My first treatment went without incident. My second treatment, I had a reaction to it and the nurse had shut the infusion down. The team came in, the care team came in and gave me …Benadryl and something else, I don’t know what it was, and waited about 30 minutes or so and resumed the infusion without incident. Everything was fine. I received my infusions every two weeks, and everything was fine, until maybe a year later I had a second reaction and we lowered … not the dosage, but maybe the drip time of the dosage. Dr Jain could tell you, maybe it was the dosage and the drip time, but we lowered it a little bit and I never had a reaction again. But I always had to have Benadryl and Tylenol with it. And that helped very much, and I got through it very well without any of the harsh [adverse] effects of the chemotherapy. My body responded quite well to it. My daily functions were fine without the [adverse] effects of the chemotherapy. So, I got through it quite well and I was very pleased with the result.

Rohit Jain, MD, MPH: That’s very good to hear. And during this treatment journey on the maintenance avelumab, how often were you seeing your physician or the nurse practitioner for follow-ups?

Jeffrey Ehas: Every 2 weeks I saw the nurse practitioner, I did my blood draw. We would discuss the blood clinic results and we would decide whether I was fit for treatment or not. And…I was always fit for treatment, everything went well. My blood work was good, and I did my treatment, and everything [went] well. I was very pleased.

Rohit Jain, MD, MPH: That’s good to hear. And that’s what I think the benefit of the switch maintenance is that now you are doing a less toxic treatment with [fewer adverse] effects, which is not affecting your quality of life. That allows you to stay on treatment for as long as possible.

Transcript is AI-generated and edited for clarity and readability.

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