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While neoadjuvant therapy has been commonplace in tumor types such as breast cancer, only with the more recent advent of effective immune checkpoint inhibitors and targeted therapy has neoadjuvant therapy been explored in melanoma. Neoadjuvant therapy in melanoma has been under investigation in clinical trials for patients with resectable stage III/IV disease; however, the SWOG 1801 trial, presented by Dr. Sapna Patel at ESMO 2022, pushed neoadjuvant treatment into the standard-of-care treatment paradigm.

SWOG 1801 answered a basic but fundamental question: if we start standard-of-care anti PD-1 prior to surgery rather than waiting until the post-op setting, will patients benefit? The answer was yes, but important questions for neoadjuvant therapy remain.

As noted in a recent review in the , while SWOG 1801 demonstrated an event-free-survival benefit of neoadjuvant pembrolizumab followed by adjuvant pembrolizumab over adjuvant therapy alone, multiple neoadjuvant studies have demonstrated an improved pathologic complete response rate with combination therapy over anti PD-1 alone. Now that the field has data to prove benefit with neoadjuvant versus adjuvant therapy, the ideal regimen balancing response and toxicity rates has yet to be determined.

Ongoing studies are assessing novel combinations and regimens but historically it has been challenging to compare across trials due to various lengths of treatment, lack of standard-of-care adjuvant therapy, and different endpoints. Guidelines through the International Neoadjuvant Melanoma Consortium aim to standardize pathologic endpoints and bring standardization to the field.

Neoadjuvant therapy also further emphasizes the need for collaborative discussions and treatment planning between dermatologists, surgeons, and medical oncologists aided by radiologists and pathologists like never before.

Ideally, biomarkers under investigation now in neoadjuvant studies will emerge to provide data-driven patient selection for neoadjuvant therapy. This will continue to be an active area of clinical research as we ascertain the ideal patient and regimens for long-term benefit in patients with locally advanced but resectable melanoma.

Meredith McKean, MD, MPH, is a clinical investigator in the Melanoma and Skin Cancer Research Program at Sarah Cannon Research Institute, Tennessee Oncology, in Nashville.

Read the review here and an interview about it here.