Carlo Contreras, MD, a surgical oncologist for Skin and Soft Tissue Cancers, a member of the Translational Therapeutics Program, medical director of Ambulatory Services at The Ohio State University Comprehensive Cancer Center (OSUCCC)–James, and an associate professor in the Division of Surgical Oncology at The Ohio State University, discusses how continued investigations in desmoplastic melanoma could better inform the use of surgical resection in select patients.

Surgical management is considered the standard first-line treatment approach in primary cutaneous melanoma. However, it can be associated with a higher risk of local recurrence. Future research in desmoplastic melanoma could address this challenge by improving the identification of patients who may not require surgical resection after successful completion of neoadjuvant therapy, Contreras begins. Moreover, it is important to better guide the extent of melanoma excision required for a given patient, Contreras says, adding that the differentiation of this subgroup is especially challenging within desmoplastic melanoma.

Although recent data have shown that bypassing immediate surgical resection can still lead to encouraging responses, many patients will still experience disease recurrence in the absence of resection, Contreras explains. Such patients may outwardly exhibit a complete clinical response, but this does not always correlate with a complete pathologic response upon review, Contreras continues. These patients will instead continue to experience disease progress on initial neoadjuvant treatment, he says. Accordingly, this patient population is considered high risk, Contreras notes.

Instead of progressing to immediate surgical resection, these patients who did not favorably respond to initial neoadjuvant treatment could first undergo dose escalation of their neoadjuvant regimen, Contreras says. This approach may provide greater benefit to high-risk patients compared with an aggressive systemic regimen, Contreras states. However, if the tumor is encroaching upon essential anatomical structures, these patients may still benefit from earlier, more aggressive surgical resection, Contreras concludes.

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Carlo Contreras, MD, discusses how continued investigations in desmoplastic melanoma could better inform the use of surgical resection in select patients.
 

Dr. Contreras on the Use of Surgical Resection in Desmoplastic Melanoma

Carlo Contreras, MD, a surgical oncologist for Skin and Soft Tissue Cancers, a member of the Translational Therapeutics Program, medical director of Ambulatory Services at The Ohio State University Comprehensive Cancer Center (OSUCCC)–James, and an associate professor in the Division of Surgical Oncology at The Ohio State University, discusses the role of neoadjuvant pembrolizumab (Keytruda) for the treatment of patients with desmoplastic melanoma.

The phase 2 SWOG 1512 trial (NCT02775851) evaluated the efficacy and safety of pembrolizumab in patients with desmoplastic melanoma. The trial included patients with both resectable and unresectable disease.

In cohort A, patients with resectable desmoplastic melanoma received 200 mg of intravenous pembrolizumab once every 3 weeks for 3 cycles in the neoadjuvant setting, and, if they were eligible for resection, then proceeded to surgery. Those who experienced progression received 1 more cycle of pembrolizumab. In cohort B, patients with unresectable desmoplastic melanoma were given pembrolizumab once every 3 weeks for up to 34 cycles, or until disease progression or unacceptable toxicity.

Data presented at the 2022 ASCO Annual Meeting showed that among 29 patients with resectable desmoplastic melanoma, the pathologic complete response rate was 55%, meeting the primary end point of the trial. As of data cutoff, the median overall survival was not yet reached.

When considering the pivotal SWOG 1512 trial, findings also need to be taken in context with the phase 2 SWOG 1801 trial (NCT03698019), which evaluated adjuvant pembrolizumab alone vs neoadjuvant and adjuvant pembrolizumab in patients with stage III or IV, high-risk melanoma, Contreras explains.

When looking at the all-comers with cutaneous melanoma enrolled in SWOG 1801 and the specific population with desmoplastic melanoma in SWOG 1512, these patients achieved promising response rates to adjuvant immunotherapy, Contreras continues. Given these results, clinicians could individualize the extent of the operation after neoadjuvant therapy, based on the response of a given patient, Contreras concludes.

Carlo Contreras, MD, discusses the role of neoadjuvant pembrolizumab for the treatment of patients with desmoplastic melanoma.


Dr. Contreras on the Role of Neoadjuvant Pembrolizumab in Desmoplastic Melanoma

Carlo Contreras, MD, surgical oncologist, The Ohio State University Comprehensive Cancer Center (OSUCCC)–James, discusses areas of planned and ongoing research with neoadjuvant therapies in basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC).

Although unmet needs in BCC and CSCC lie in head-to-head, randomized clinical trials with hedgehog inhibitors, it is unlikely that that this will be explored in the future, Contreras explains. However, researchers are attempting to replicate promising results from earlier trials in new, larger trials for patients with CSCC and BCC.

-directed therapy in melanoma demonstrate high pathologic complete response rates (pCRs), but also increased risk for short-term recurrence 2 years post-surgical resection, Contreras explains. Accordingly, evaluating long-term data from neoadjuvant trials in CSCC and BCC may reveal the risk of recurrence in this disease setting.

Overall, it is hoped that future research will result in more durable responses than what has been previously seen, he concludes.

Carlo Contreras, MD, discusses areas of planned and ongoing research with neoadjuvant therapies in basal cell carcinoma and cutaneous squamous cell carcinoma.

Carlo Contreras, MD

Articles

Dr. Contreras on the Use of Surgical Resection in Desmoplastic Melanoma

Dr. Contreras on the Role of Neoadjuvant Pembrolizumab in Desmoplastic Melanoma

Dr. Contreras on Neoadjuvant Therapies in Basal Cell Carcinoma and Cutaneous Squamous Cell Carcinoma