CheckMate 274 Follow-Up Supports the Use of Adjuvant Immunotherapy in Bladder Cancer

Lindsay Diamond, MSN, AGNP-C, AOCNP

Long-term data readouts from trials evaluating immunotherapeutic approaches in bladder cancer are changing the landscape, according to Lindsay Diamond, MSN, AGNP-C, AOCNP. Specifically, extended follow-up results from the CheckMate 274 trial (NCT02632409) demonstrated that nivolumab (Opdivo) following surgery greatly improved disease-free survival (DFS) rates in patients with high-risk muscle invasive urothelial carcinoma. Findings were presented at the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) by Diamond’s colleague Matthew D. Galsky, MD, FASCO.

At a follow-up of 36.1 months, patients with PD-L1 expression of 1% or greater experienced a median disease-free survival (DFS) of 52.6 with adjuvant nivolumab (n = 140) vs 8.4 months with placebo (n = 142; HR, 0.52; 95% CI, 0.37-0.72). Moreover, the median non–urothelial tract recurrence-free survival was 52.6 vs 8.4 months (HR, 0.53; 95% CI, 0.38-0.74), and the median distant metastasis–free survival was not reached vs 20.7 months (HR, 0.58; 95% CI, 0.40-0.84), respectively.

With the same follow-up time, patients in the intention-to-treat population receiving adjuvant nivolumab (n = 353) compared with those receiving placebo (n = 356) experienced a median DFS of 22.0 vs 10.9 months (HR, 0.71; 95% CI, 0.58-0.86) median non–urothelial tract recurrence-free survival of 25.9 vs 13.7 months (HR, 0.72; 95% CI, 0.59-0.88) and a median distant metastasis–free survival of 47.1 vs 28.7 months (HR, 0.74; 95% CI, 0.60-0.92), respectively.

Diamond explained that the data “support the use of [adjuvant nivolumab] not only in patients who are PD-L1 positive, but also in the intention-to-treat population. It’s exciting to show where adjuvant immunotherapy and maybe even adjuvant immunotherapy combinations might be going in the future.”

In an interview with Oncology Nursing News®, Diamond, a nurse practitioner and clinical program manager of the GU Oncology Clinical Trials Department at the Icahn School of Medicine at Mount Sinai, contextualized the findings from the trial and weighed in on the overarching trajectory of bladder cancer research from a practitioner’s perspective.

Oncology Nursing News: How has the use of immunotherapies evolved in recent years?

Diamond: I’ve been working in GU oncology—specializing in bladder cancer—since 2015. When I originally came into the field, immunotherapy was still emerging in the metastatic setting and it was new and there were all these approvals, but we didn’t have any immunotherapy early on in the neoadjuvant or adjuvant setting. I thought, if immunotherapy works in the metastatic setting, why wouldn’t it work earlier on? Of course, the answer to that is much more complex, but it was a great question. I was in the practice at Mount Sinai when the CheckMate 274 trial was being run as a clinic nurse, so I wasn’t involved in the clinical trial, but it was awesome seeing patients get access to immunotherapy earlier on, [since], previously, they hadn’t been able to get that.

How do the CheckMate 274 long-term efficacy findings support nivolumab’s use in clinical practice?

When the original study read out, there was about a 6-month minimum follow-up. We knew that there was improvement in DFS and that was great. We could give adjuvant nivolumab and [patients] didn’t need any treatment for 6 months or so; we’d watch closely, and see what happens.

There is this mentality when patients have localized disease, of ‘well, it's not metastatic and you had it removed so you're fine,’ but those patients still live with cancer every day of their life after that surgery and it's a waiting game. Every day they’re waiting, every scan they’re waiting [thinking] ‘when’s it going to come back?’ So you can give them an extra 6 months and that’s great—but there's still that cloud hanging over them.

This read out, at approximately 31 to 32 months, [showed] the DFS in patients who received nivolumab was 22 months vs 10 months [with placebo]. That’s double. Now you’re talking approximately 2 years. [For] those patients that were PD-L1 positive, you’re talking approximately…52 months [DFS]. That is a 6-times increase in DFS by receiving adjuvant nivolumab.

Numbers are great, researchers and doctors love to use numbers, but what does that mean for a patient? That's X amount of years vs X amount of months, but it’s also another birthday, another grandchild being born, another Christmas. When you start looking at what it gives these patients, it's so much more than months on a calendar. Particularly in that PD-L1–positive group [who had a DFS of] 8 months vs 52 months [with placebo vs nivolumab]—those are numbers we don’t typically see in cancer clinical trials when comparing an arm to a placebo, it’s impressive.

As a nurse and someone that talks to patients about consenting and risk benefit, watching how the study reads out, [I wonder] will this effect continue to last and, if so, how long? How long can we delay disease recurrence, metastatic disease, and will it eventually read out to overall survival benefit?

In your experience are patients at hesitant to initiate immunotherapy following surgery and if so, what conversations do you have about the treatment?

Having been doing this for a while, I was always part of the conversation [regarding] adjuvant chemotherapy and that conversation is a little bit harder because no matter how far we’ve come in terms of managing chemotherapy’s adverse effects, there is a stigma from the 70s, 80s, and 90s that chemotherapy is toxic and hard to tolerate, you lose your hair, you can't work, etc. [Patients ask:] ‘Why would I do that for only 6 months of DFS?’

Immunotherapy is a little bit different because we, as providers, know that 30% of patients or so could have a serious immune related adverse effect from immunotherapy, but the majority of patients are going to do fine on it. Immunotherapy is advertised as this easy treatment that uses your immune system to treat your cancer and it has more of a positive connotation around it. The word chemotherapy is scary, the word immunotherapy is a little bit friendlier, and patients seem to be more willing to go on immunotherapy than chemotherapy.

Were there any other data from ASCO GU that were presented in the bladder cancer space that caught your attention, and in your opinion, did anything have the potential to potentially change practice?

It’s going to sound biased because I’ve worked with Dr Galsky for 8 years now, but, generally, clinical trials looking at bladder sparing approaches [are important], whether it’s our study HCRN GU16-257 [NCT03558087]—that looks at chemotherapy and immunotherapy—or other trials that look at just chemotherapy to see if there is a way that we can avoid patients from having to remove their bladder.

We know that when patients get neoadjuvant chemotherapy, 30% to 40% of the time, at the time we removed their bladder, there’s no evidence of any cancer there. That's great, but removing someone's bladder is incredibly morbid. We’ve come a long way and how we create neobladders and ostomies, but it's never your bladder. It is an entire organ and not only does it affect quality-of-life, body appearance, and self-esteem [to have it removed], but there's a high risk with the surgery. There are complications from a neobladder—they have a high risk of urinary tract infections, so it’s not a simple organ removal.

Is there a way that we can identify which patients don’t have to have their bladder removed? The HCRN GU16-257 study was super interesting in that we’re trying to establish a biomarker to identify these patients by using a clinical complete response. Other studies are doing similar trials using neoadjuvant chemotherapy.

Our trial was a bit limited because you had to have been able to receive cisplatin-based chemotherapy. These patients are already getting the approved treatment, you’re just adding immunotherapy and seeing if that has an effect and the trial did read out that there's a little bit more of a clinical complete response with the combination vs standard of care chemotherapy, but it’s early. It will be interesting to kind of see how that mode of trial crosses over to other settings such as patients who can’t receive cisplatin-based chemotherapy or don’t want to receive chemotherapy, etc, and [also] using new biomarkers, imaging tools, etc, to help identify who could receive neoadjuvant treatment of some combination, keep their bladder, maybe get some adjuvant treatment and be able to live a long life without any disease recurrence.

Are there any other unmet needs in the space?

One thing that patients always ask for is a definitive tumor marker that they can monitor. We know with prostate cancer, breast cancer, some gastrointestinal cancers, they can kind of know how they’re doing, and we don’t really have that established yet for bladder cancer. We’re telling these patients: trust us, get this treatment and, in 3 months, we’ll do a scan. Scans are great, but sometimes changes on imaging are kind of delayed to as what’s happening on a microscopic level. So, as someone [whose role] is mostly patient facing, I hope that we could eventually develop some type of tumor marker that we can [use] track to monitor patient statuses in between scans.

Reference

Galsky MD, Witjes JA, Gschwend JE, et al. Extended follow-up results from the CheckMate 274 trial. J Clin Oncol. 2023;41(suppl 6):LBA443. doi:10.1200/JCO.2023.41.6_suppl.LBA443