“The effect size for adjuvant nivolumab versus placebo across primary, secondary, and exploratory endpoints is all remarkably stable,” says Matthew D. Galsky, MD.
In this video, Matthew D. Galsky, MD, provides follow-up data on the CheckMate 274 trial, which showed continued benefit of adjuvant nivolumab in patients with high-risk muscle-invasive urothelial carcinoma. The findings were presented at the 2023 ASCO Genitourinary Cancers Symposium in San Francisco, California. Galsky is the director of genitourinary medical oncology at Tisch Cancer Institute and a professor of medicine at the Icahn School of Medicine at Mount Sinai in New York, New York.
For patients with muscle invasive urothelial cancer of the bladder or upper urinary tract, surgery is the standard treatment. We know that patients, despite surgery, have a high risk of metastatic recurrence. We can define patients at high risk based on pathological stage criteria. Patients who have received neoadjuvant chemotherapy if there's pathological T2 or higher disease in the surgical specimen, we know that confers a high risk of recurrence, and patients who haven't received neoadjuvant chemotherapy and are ineligible for cisplatin based chemotherapy, if there's pathological stage T3 or higher disease that confers greater risk for recurrence.
In the past, we haven't had adjuvant treatments to give after surgery to try and mitigate risk in those patient populations. That's why CheckMate 274 was designed, to try and address that unmet need. CheckMate 274 randomized both of those patient populations to receive either adjuvant nivolumab, a PD-1 inhibitor for up to 1 year of treatment, or placebo. Their co-primary endpoints were disease free survival in all randomized patients and disease free survival in patients with tumor PD-L1 expression ≥1%.
The initial results of the study have been presented in the past published in the New England Journal of Medicine, led to the FDA approval of adjuvant nivolumab in this space. That was with a minimum follow up of 5.9 months. Now we're presenting a minimum follow up data with 31.6 months, median follow-up with 3 years now, really showing that adjuvant nivolumab improves disease free survival in both of those co-primary endpoint populations, all randomized patients, in patients with tumor PD-L1 expression ≥1%, with an effect size that's almost identical to slightly better than what was shown in the initial data.
So I think 2 key findings there. There's a lot of interesting findings from some of the longer-term follow-up data that's presented, but probably 2 key findings. One is that the benefit is sustained despite a fixed duration of treatment, so adjuvant treatments given for a fixed duration of time. Now with 3-year follow-up, one would want to see that the benefits of that treatment are sustained even after it was discontinued. That's of course what we see. The effect size for adjuvant nivolumab versus placebo across primary, secondary, and exploratory endpoints is all remarkably stable.
The other interesting finding is an endpoint that is presented for the first time in this presentation, and that's PFS2, or progression free survival 2. Basically that's measured from the time of randomization to the time of progression on subsequent next-line treatment. So for instance, a patient who's randomized to placebo, develops metastatic disease, receives immune checkpoint blockade for frontline treatment of metastatic disease, and then progresses. So measured at that endpoint. PFS2 is actually improved with adjuvant nivolumab versus placebo in both the intent-to-treat population and in patients with tumor PD-L1 expression ≥1%, meaning that what you do in the adjuvant setting impacts the natural history of the disease in such a way that it even impacts outcomes when patients receive their next line of treatment.
This transcription was edited for clarity.