This morning I had the opportunity to present the results of IMvigor 210 which is a phase II trial of a novel anti-PD-L1 agent, an immunotherapy compound, in patients with metastatic urothelial carcinoma or locally advanced urothelial cancer. These patients had been on first line cisplatin or carboplatin-based chemotherapy and they progressed either on or following that chemotherapy. They were treated in the second line or beyond, so they could have had other chemotherapy regimens, with atezolizumab. This was a single arm trial so all patients that were enrolled onto the trial received trial therapy.
Are there other options in this setting?
The other FDA approved agents that improve overall survival benefit for patients who failed platinum based chemotherapy are none. So all the chemotherapy that we give in the setting is palliative and much of it has toxicity. These patients tend to be older, frail and have comorbidities, either from their cancer or from the previous treatment of their cancer like peripheral neuropathy in their hands, renal insufficiency and other diseases. So they’re a challenging population to treat with chemotherapy.
How many patients did you look at?
311 patients were treated in cohort 2 on IMvigor 210.
What was the method?
Patients in this category who have failed platinum based chemotherapy were enrolled onto the study. They had to have a reasonable performance status or functional status. They could have had, as I mentioned, any prior number of lines of chemotherapy and importantly they could also have pre-existing renal impairment that really limits our ability to treat patients with systemic chemotherapy sometimes. Everyone on trial submitted tumour tissue that was either archive tumour tissue or fresh biopsies for biomarker testing for PD-L1 which is the target of atezolizumab. They did that in screening so we had the results of all of that data but both investigators and patients were blinded. Patients were then, if eligible, treated on protocol therapy with intravenous atezolizumab once every three weeks. They had assessment by CT scans MRIs every nine weeks during therapy and in cohort 2 as long as they were deriving a clinical benefit patients were able to stay on therapy until the investigator felt like the patient was no longer deriving clinical benefit, the patient withdrew from the study. Given the fact that there are no FDA approved agents in this setting, this was a reasonable approach.
The study had two primary endpoints, one is a traditional endpoint of RECIST response criteria, another one was modified RECIST which really does capture some of the atypical response patterns that we see with immunotherapy. For the entire population the objective response rate was 15% and for those selected patients who over-expressed the target of PD-L1 there were two or three patients with greater than 5% expression, the response was 26% and this included 11% that had a complete response which is really unprecedented in second line and beyond urothelial cancer trials.
What is the potential impact of this research so far?
The numbers are impressive and certainly met the primary endpoint which was above 10% which is the benchmark for historical control chemotherapy studies in the second line and beyond. But beyond just the number of the response it was really the durability of the response with patients staying on protocol therapy really beyond what is expected when you compare to chemotherapy studies. This included not just the patients who were traditionally responding to chemotherapy with a shrinkage of their tumour but people who had measurable stable disease. So those patients seem to be benefitting as well.
What is the take home message?
The message for doctors watching is that there’s interest and there are agents that are for the first time in many, many years looking like they’re going to have an impact on the treatment of these cancers. I think it’s exciting that so many different investigators and different sponsors are looking at urothelial cancer and so I’m looking forward to what’s to come in the next years.
