Roundtable Roundup: Skin Cancer

Case Summary

• A 78-year-old man had a history of stage III melanoma.
• Patient underwent surgical resection 12 years prior.
• Lymph node dissection was positive for nodal involvement.
• Patient declined complete lymph node dissection and adjuvant systemic therapy.
• Patient remained active since his surgery and maintained regular follow-up.
• On routine follow-up, the patient presented with moderate asthenia that limited his daily activities, without other relevant clinical symptoms.
• ECOG performance status: 1
• Physical examination was unremarkable.
• Notable laboratory findings: lactate dehydrogenase (LDH) level of 380 IU/L (reference range, 110-240 IU/L)
• A full-body CT scan revealed the presence of pulmonary and hepatic nodules but no evidence of brain metastases.
• The patient underwent a core-needle biopsy of the largest hepatic lesion in segment IVb without any complications.
• Pathology revealed metastatic melanoma.
• Mutation testing was BRAF negative.

TAWBI:The decision-making here was reasonable and appropriate. Either of those regimens technically would be appropriate for this patient. I would probably say the patient’s high LDH is the biggest [factor]. I also recognize that as you start using a new combination more consistently…people’s perception of the combination changes as they became more familiar with it.

In the National Comprehensive Cancer Network [NCCN] guidelines, they list nivolumab and relatlimab-rmbw [Opdualag] as a preferred regimen.¹ They only added category 1 recently. I was [surprised] at the NCCN not adding category 1 evidence from the get-go because the randomized, phase 2/3, blind, independent review study [RELATIVITY-047; NCT03470922] hit its primary end point.²

That to me made it a category 1 regimen, so I’m happy [the NCCN recognizes] this is category 1 evidence. In the NCCN guidelines, you can technically choose any of those combination regimens or single-agent PD-1 inhibitors; that’s the current recommendation.

The low-dose ipilimumab [Yervoy]/pembrolizumab [Keytruda] was mentioned there. I’d be very careful because there have never been randomized studies for low-dose ipilimumab/pembrolizumab, and there's only been 1 nonrandomized phase 2 trial.

WARNER: The way I think about this, when I talk about this with my patients, is we now have 3 options. We have single-agent PD-1 inhibitors, we have nivolumab/relatlimab, and then we have ipilimumab plus nivolumab [Opdivo]. I don’t give a ton of low-dose ipilimumab plus PD-1 anymore because we have nivolumab/relatlimab, but that’s also a fourth option.

There’s a spectrum of increased response rates, but that correlates exactly with an increased rate of toxicity. So I think treatment is highly dependent on what your patient can tolerate and is willing to tolerate. I think there are times [when] it’s the wrong decision to give combination—[for example], in frail patients, [very old patients], someone who has a history of autoimmune disease, those types of things. I do think if they have low disease burden in not a dangerous place in their body that it’s probably the wrong decision to give them full-dose ipilimumab/nivolumab. But could you be faulted for doing it? No, it just wouldn’t be my clinical decision in that situation.

"What first-line therapy are you most likely to recommend for this patient with metastatic melanoma with no BRAF-activating mutation?"

_REFERENCES:

_{NCCN. Clinical Practice Guidelines in Oncology. Melanoma: cutaneous, version 2.2023. Accessed June 19, 2023. https://bit.ly/3NivRJS}

_{Tawbi HA, Schadendorf D, Lipson EJ, et al; RELATIVITY-047 Investigators. Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma. N Engl J Med. 2022;386(1):24-34. doi:10.1056/NEJMoa2109970}