Checkpoint inhibitor therapy benefits advanced bladder cancer patients
Dr Arjun Vasant Balar - NYU Langone Medical Center, New York, USA
The abstract that I presented this morning was the initial presentation of IMvigor210 cohort 1. This particular trial tested atezolizumab as first line therapy in cisplatin ineligible patients with metastatic urothelial cancer. The background that is very important for viewers to know is that cisplatin-based chemotherapy is the standard of care in metastatic urothelial cancer, however a significant proportion of patients will be ineligible due to poor performance status, impaired kidney function. We use gemcitabine most commonly as the most commonly used regimen in this setting. PD-L1 is an important target in bladder cancer and targeting this particular target has shown activity in the previously treated setting.
IMvigor210 cohort 1 focussed on patients with locally advanced or metastatic urothelial cancer with predominant urothelial cancer histology and enrolled 119 patients who were previously untreated in the metastatic setting and were considered cisplatin ineligible. Patients received atezolizumab at 1200mg every three weeks until RECIST defined disease progression. The key findings of this trial were that the objective response rate in the 119 patients was 24% and 7% of patients achieved a complete response. When we looked at the responses across all PD-L1 expression level subgroups what we found was that responses were actually observed in all subgroups, including patients with the lowest level of expression, IC0. We saw 21% of those patients achieve an objective response and 8% of those patients achieve a complete response. At a median follow up of 14.4 months 75% of these responses overall are still ongoing. Further, a median estimated survival at this point is 14.8 months for a yet immature data set because only 47% of the events have occurred, suggesting that this number might actually improve further over time.
Lastly I’ll finish on the safety of this therapy. What we found was that therapy was exceptionally well tolerated with only 15% of patients developing a grade 3 or 4 treatment related adverse event and only 6% of patients discontinuing therapy due to an adverse event.
So, in summary, these data show us that responses with atezolizumab in patients with metastatic urothelial cancer who are cisplatin ineligible showed responses in 24% of patients; 75% of these responses were durable and still ongoing. We found that the median estimated survival at this point is 14.8 months which compares very favourably with gemcitabine and carboplatin which has a median survival of 9-10 months and yet these data are immature, suggesting that this might improve over time. Overall, therapy was extremely well tolerated with a low rate of treatment related adverse events grade 3 and 4 and a low rate of treatment discontinuation due to adverse events. So, in summary, these data provide a compelling argument for atezolizumab to become a potential new standard of care for patients with metastatic urothelial cancer who are cisplatin ineligible.
PD-L1 and PD-1 therapy has been very prominent through this year’s ASCO, and many other conferences as well, as monotherapy and also through combination therapy. Is that something that you could see following up with bladder cancer?
Absolutely. I think one thing that many of us in this particular field who have been treating bladder cancer see, especially with these data that are being presented, that immunotherapy will become increasingly a backbone of some form of therapy, whether it be first line or second line in metastatic bladder cancer. We also know that while these data are very promising, this is still only a first step which means the future will likely be some form of combination strategy, either with other immune modulatory agents or in combination with other immune potentiating agents such as low dose chemotherapy, radiation and also sequencing will be very important. But in the future immunotherapy will certainly be a cornerstone of therapy in metastatic disease.