Immunotherapy Treatment Options in High-Risk or Locally Advanced/Metastatic Non-melanoma and Melanoma: An Evolving Treatment Landscape

Session Overview and Presentation Highlights

Exploring Immunotherapy Treatment Options in High-Risk, Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma

The panel was presented with study design, efficacy, and safety data from several prospective and retrospective cemiplimab studies. Five-year results from the KEYNOTE-629 trial (NCT03284424; pembrolizumab) were reviewed, and data related to high-risk CSCC were presented. Faculty were asked about their impressions of the data, insights into their treatment patterns in the mCSCC population, their opinions about who would benefit most from neoadjuvant immunotherapy, and their practice patterns related to adjuvant therapy.

Resectable and Advanced/Metastatic Cutaneous Melanoma Immunotherapy Treatment Options

Data from trials were presented from clinical trials of neoadjuvant treatment in stage II-IV melanoma and first-line metastatic or unresectable melanoma, and faculty were asked to share their impressions of the data and their approach to treating patients in these populations. They also shared theirchallenges when using dual immunotherapy and the role of PD-L1 and LAG-3 in their practices. Newer treatments were reviewed, such as tumor-infiltrating lymphocyte (TIL) therapy and RP1 in recurrent melanoma; factors impacting treatment decisions were shared, along with unmet needs in this treatment space.

Discussion Themes/Summary

While patients are having early, deep responses in frontline mCSCC, the optimal duration of treatment has not been determined, leading to variations treatment cessation in those patients. Faculty acknowledged that while head and neck SCC is being treated efficiently, other sites (eg, mucosal areas, feet), are not as likely to respond.

Faculty identified unknowns that may have contributed to the negative results of the KEYNOTE-630 trial (NCT03833167), including how many patients had head and neck cancers, percentage of cancers that were UV-induced, and the increased number of T3 lesions in KEYNOTE-630 compared with the C-POST trial (NCT03969004). It was also speculated that C-POST may be more sensitive for recurrence rate.

The success of neoadjuvant therapies was highlighted, with faculty sharing that in patients with a complete response (CR), surgery may not be needed or it can be used as rescue therapy if CR is not reached. Further, there was optimism that neoadjuvant therapy may eventually render adjuvant treatment irrelevant or needed only for those who don’t respond to neoadjuvant therapy.

Opinions varied widely on faculty preference between neoadjuvant pembrolizumab vs ipi-nivo in melanoma, degree of response, recurrence, therapy switching, and sequencing with BRAF/MEK, indicating that additional data are needed in this area. Faculty agreed that patients who have a complete response do well for a long time and may not need ongoing therapy.

The determination of frontline use of ipi-nivo vs rela-nivo is based on patient characteristics, with ipi-nivo preferred for brain metastasis, high tumor burden, mucosal melanoma, and high LDH. But overall, there was no consensus on preference. Many panelists expressed the belief that rela-nivo will replace PD-1 monotherapy.

There is interest in the broader use of ctDNA; at present, it is not used routinely and is considered only for research. Broader application may inform decisions to stop therapy in metastatic or adjuvant settings or to de-escalate therapy.

While some faculty see the potential of TIL therapy, there was a widespread negative opinion of the phase 2 lifileucel trial in advanced melanoma (C-144-01; NCT02360579).

Unmet Needs and Recommendations

• While some panelists are using PD-L1, LDH, and ctDNA, there is a need for biomarkers to assist with treatment selection and monitoring.
• More treatment options are needed in the PD-1 refractory setting.
• Real-world research can provide insight related to resistance, sequencing, and optimal duration of therapy.

References

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