A medical oncologist discusses the findings of three clinical trials presented during the 2019 American Society of Clinical Oncology Annual Meeting.
More than 80,000 new cases of bladder cancer will be diagnosed this year in the United States, according to the American Cancer Society; however, patients now have newer treatment options to help fight the disease.
At the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Dr. Guru Sonpavde, a medical oncologist at Dana-Farber Cancer Institute in Boston, told CURE® about the most recent advancements
CURE®: Can you provide highlights of some of the most practice-changing bladder cancer studies presented during ASCO?
Sonpavde: One of the major highlights was the data regarding enfortumab vedotin, (which is) an antibody-drug conjugate that targets nectin-4, a molecule on the surface of bladder cancer cells. These data come, of course, on the heels of the approval of (Balversa [erdafitinib]), which is approved for patients, just within a couple months ago, with FGFR3 or FGFR2 alterations that include mutations and fusions.
Now comes the data with enfortumab vedotin, which was a phase 2 trial of around 125 patients that essentially confirms the data that we saw earlier in the phase 1b trial showing in patients that were post-platinum and post PD-1/PD-L1 inhibitors an approximately 40% response rate. What was also impressive was there was a complete response rate in 9% of patients and they were robust responses in patients with liver metastases. So, we look forward to the use of this drug and hopefully we will be able to use it soon based on these data. There is a confirmatory phase 3 trial that is ongoing comparing enfortumab versus chemotherapy in the post-platinum and post PD-1/PD-L1-exposed patients.
I also wanted to highlight a novel strategy of switch maintenance therapy, which was a randomized phase 2 trial. These were patients who had finished first-line platinum-based chemotherapy — about four cycles of platinum-based chemotherapy at least — and had stable disease or better. The normal strategy is to wait for patients to progress and then deliver second-line therapy, but in this study the patients underwent a switch maintenance strategy comparing (Keytruda [pembrolizumab]) versus placebo in this setting. It was very promising. The results showed an improvement in progression-free survival going from 5.5 months median to approximately 8.0 months median.
The third trial I wanted to highlight was a phase 3 trial. (Although it) is not practice-changing, it still informs us regarding further drug development. The phase 3 trial compared first-line cisplatin/gemcitabine combined with either placebo or (Avastin [bevacizumab]). The primary endpoint of survival was not extended but adding bevacizumab to cisplatin-based chemotherapy (showed) a median survival of around 14.0 months in both arms. There was (also) a modest improvement in progression-free survival.
What can be done with this information going forward?
There are trials now trying to combine cisplatin-based chemotherapy with PD-1/PD-L1 inhibitors in the neoadjuvant (administering before main treatment) space. A phase 3 trial (that’s in progress) is looking at gemcitabine/cisplatin as a standard in the neoadjuvant space compared with gemcitabine/cisplatin plus (Opdivo [nivolumab]), a PD-1 inhibitor, and there is a third arm that is planned that is going to combine gemcitabine/cisplatin plus nivolumab plus an IDO1 inhibitor, which also enhances the immune state by inhibiting the IDO1 enzyme. So, we will wait and see the results of this phase 3 trial and other phase 3 trials. There are also trials looking at the immunotherapy-alone approach — a chemotherapy free approach for cisplatin ineligible patients where there is nothing approved at the moment.
Can you speak to Balversa for such a specific population of patients?
In the post-platinum space, with patients who had FGFR3 mutations or infusions, FGFR2 mutations or infusions, there was a dose escalation strategy which might have led to better dosing in more patients. The drug is active — (there is) a response rate in the 30% to 40% range in this patient population. The duration of response was a median of around six months. There are some unique toxicities with this agent, (such as) hypercalcemia and hand/foot syndrome, but they are manageable. And most were grade 1 or grade 2. And a third (toxicity) that is somewhat unique, and oncologists have not really been exposed to this with other agents, is central serous retinopathy, (which is) an eye toxicity that causes a central visual defect. But overall, it’s a highly manageable toxicity.