Retrospective Study Shows Nivolumab Associated With OS Benefit After Nivolumab/Ipilimumab irAEs in Advanced Melanoma

Maintenance treatment with nivolumab (Opdivo) monotherapy was associated with improved overall survival (OS) vs the permanent discontinuation of nivolumab in patients with advanced melanoma following a treatment hold of the combination of nivolumab and ipilimumab (Yervoy) due to immune-related adverse effects (irAEs), according to data from a retrospective study presented at the 2023 ASCO Annual Meeting.

Findings indicated that patients who resumed nivolumab monotherapy after the resolution of toxicity and completion of steroid taper (n = 46) experienced a 68% reduction in the risk of death compared with those who did not resume nivolumab (n = 76; HR, 0.32; 95% CI, 0.12-0.84).

In those who resumed treatment, 12 patients (26%) experienced any-grade irAEs, including 5 patients who had grade 3 irAEs. However, there were no reported cases of grade 4 or 5 irAEs, and a recurrence of the same irAE was reported in only 1 patient.

“It is safe to resume nivolumab after [treatment with the] combination of ipilimumab/nivolumab. There are some patients who seem to benefit from doing so. Who those patients are and [knowing] when [nivolumab should be continued] is still to be determined at this point. However, [resuming nivolumab] is something that should be considered when you're faced with a patient who's had a toxicity that has resolved, if you feel like it might be beneficial to the patient,” study co-author Elizabeth I. Buchbinder, MD, said.

In an interview with OncLive^®, Buchbinder explained why differing real-world practice patterns prompted the investigation of nivolumab maintenance therapy in patients with advanced melanoma who had severe irAEs during combination treatment with nivolumab and ipilimumab, expanded on findings derived from the investigation, and highlighted why prospective data are likely needed to further support these data. Buchbinder is an assistant professor of medicine at Harvard Medical School and a senior physician of medical oncology at Dana-Farber Cancer Institute in Boston, Massachusetts.

OncLive: What is the standard practice for patients with advanced melanoma who experience irAEs during frontline treatment with the combination of ipilimumab and nivolumab?

Buchbinder: A lot of our patients who are treated with the combination of ipilimumab and nivolumab in the frontline setting who have metastatic melanoma develop toxicity after 1 to 3 doses. Usually what that means is that the treatment gets stopped, the patient gets started on steroids or other immunosuppressive therapy, and then after that's tapered, we have a decision to make.

A lot of times on [clinical] trials, once a patient had a bad toxicity, they never went back on immunotherapy. However, at that point, patients [may] still have had residual disease on [imaging]. They might have had some shrinkage, stable disease, or even some growth, so they still had active melanoma on their scan. The decision is: do you just watch the patient, or do you think about trying to add more immunotherapy?

What questions were investigators aiming to address by launching this research?

What some providers do is give more nivolumab. At that point, they will give nivolumab alone. We know a lot of the toxicities are probably from the combination of ipilimumab and nivolumab, and as a result, you can safely give the nivolumab. Other [practitioners] will say that until a patient progresses, they will just watch them because they had toxicity on ipilimumab/nivolumab.

Therefore, we wanted to answer the question [regarding the appropriate strategy] because there's a difference in practice with different providers. We don't know what's better, and we don't know what might lead to better outcomes for patients.

We realized that there were some differences in practice that weren't necessarily based on patient factors; [rather], they were based on physician factors. In potentially identical patients, some physicians were making decisions to continue [nivolumab], and some [were not]. We went back and did this analysis of patients who did and did not resume nivolumab, and we were surprised to find that there was quite a difference in terms of the survival of those 2 groups, which was really interesting.

Could you expand on the patient population and the methods of this investigation?

This was a retrospective study, so [these data] still need to be prospectively validated or must include much larger numbers before we start changing practice. However, it's very thought provoking. There are definitely differences in terms of how different providers are [approaching the continuation of nivolumab] around the country and around the world. There's a lot still to be done in this space. Hopefully, we've started the conversation, and this [could] lead to more research in this area.

What were the findings from this study?

OS was better for the group where the nivolumab was resumed after completion of steroid taper or completion of other immunosuppressive therapy for irAEs. As a result, it does suggest that giving more immunotherapy after resolution of toxicity is worthwhile.

In addition, within that group [that continued nivolumab monotherapy], we did not see a huge increase in toxicity. Twenty-six percent of those patients went on to develop other irAEs. Of those, only 1 had [a recurrence] of the same irAE that they previously had with ipilimumab/nivolumab.

What are some of the next steps and future implications of this research?

The first step will be to try to pull together an even larger series from other institutions to see if these data [trends] continue as we broaden our scope and the number of patients, building on the retrospective analysis. The problem is that this is still a retrospective analysis, so it would be nice to see if we can validate this prospectively.

Reference

Maloney A, Giobbie-Hurder A, Fograssi MC, et al. Role of nivolumab maintenance therapy in advanced melanoma patients following severe immune-related adverse events from combination nivolumab and ipilimumab. J Clin Oncol. 2023;41(suppl 16):1005. doi:10.1200/JCO.2023.41.16_suppl.9520