Suthee Rapisuwon, MD, medical oncologist, MedStar Health, discusses clinical trial barriers for patients with mucosal melanoma in the United States. 

Currently, novel combinations with immunotherapy and targeted therapy are being evaluated for efficacy in patients with mucosal melanoma, says Rapisuwon. Additionally, the utility of checkpoint inhibitors in the adjuvant setting for this patient population is the subject of ongoing research efforts, Rapisuwon explains. 

However, clinical trials devoted to evaluating novel regimens in mucosal melanoma are limited in the United States because the number of patients with this specific melanoma subtype in the United States is more limited compared with other parts of the world, Rapisuwon says. For example, in Southeast Asia and China, the majority of patients with melanoma have the mucosal subtype, whereas in the United States, a large proportion of patients have cutaneous melanoma, Rapisuwon explains. As such, it is difficult to enroll patients onto mucosal melanoma clinical trials in the United States, concludes Rapisuwon. 

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Suthee Rapisuwon, MD, discusses clinical trial barriers for patients with mucosal melanoma in the United States.  



Dr. Rapisuwon on Clinical Trial Barriers in the United States in Mucosal Melanoma 

Suthee Rapisuwon, MD, medical oncologist, MedStar Health, discusses the potential utility of toripalimab in melanoma subtypes.

Toripalimab, a PD-1 inhibitor, was developed in China, where it is currently approved for marketing, says Rapisuwon. As monotherapy, toripalimab demonstrated similar activity compared with other checkpoint inhibitors, such as pembrolizumab (Keytruda) and nivolumab (Opdivo), in patients with cutaneous melanoma. Response rates with single-agent toripalimab appear to be more modest in acral and mucosal melanoma subtypes, Rapisuwon explains.

However, on January 25, 2021, the FDA granted toripalimab a fast track designation for use in the frontline treatment of patients with mucosal melanoma.

Moreover, the regulatory designation gave the green light to an investigational new drug application for a phase 3 trial that will randomize patients with unresectable, locally advanced or metastatic mucosal melanoma to frontline toripalimab plus axitinib (Inlyta) or pembrolizumab. Previous data from a phase 1b trial (NCT03086174) demonstrated a 48.5% overall response rate with toripalimab plus axitinib in this patient population, concludes Rapisuwon.

Suthee Rapisuwon, MD, discusses the potential utility of toripalimab in melanoma subtypes.  



Dr. Rapisuwon on the Potential Utility of Toripalimab in Melanoma Subtypes 

Suthee Rapisuwon, MD, medical oncologist, MedStar Health, discusses the utility of frontline immunotherapy vs targeted therapy in acral and mucosal melanoma.

Patients with newly diagnosed acral or mucosal melanoma should undergo genetic testing to identify targetable mutations, Rapisuwon says. However, whether a patient should receive up-front targeted therapy or immunotherapy is debatable, explains Rapisuwon. 

Typically, patients will receive immunotherapy in the frontline setting because immunotherapy can confer long-term responses for patients, Rapisuwon explains. Additionally, the majority of patients with acral or mucosal melanoma do not harbor actionable alterations, Rapisuwon says. For example, approximately 20% to 30% of patients with mucosal melanoma harbor 

 mutations, Rapisuwon says. Notably, some patients have 

-positive mucosal melanoma and are eligible for BRAF or MEK inhibitors, Rapisuwon concludes.

Suthee Rapisuwon, MD, discusses the utility of frontline immunotherapy vs targeted therapy in acral and mucosal melanoma.   



Dr. Rapisuwon on Frontline Immunotherapy Vs Targeted Therapy in Melanoma Subtypes 

Suthee Rapisuwon, MD, medical oncologist, MedStar Health, discusses the biologic differences between mucosal and cutaneous melanoma. 

The initiation events differ between mucosal melanoma and cutaneous melanoma, says Rapisuwon. Unlike in cutaneous melanoma, 

 mutations are not often the phylogenetic event in mucosal melanoma, Rapisuwon explains. 

However, patients with mucosal melanoma often harbor neurofibromatosis type 1 mutations, genetic aberrations in chromosomes 5 through 12, and 

 mutations, says Rapisuwon. Moreover, these abnormalities often serve as organizing events for tumorigenesis, concludes Rapisuwon.

Suthee Rapisuwon, MD, discusses the biologic differences between mucosal and cutaneous melanoma.  



Dr. Rapisuwon on Biologic Differences Between Mucosal and Cutaneous Melanoma  

Suthee Rapisuwon, MD, medical oncologist, MedStar Health, discusses the frontline treatment of acral and mucosal melanoma.

Immunotherapy is the preferred frontline treatment option for patients with acral and mucosal melanoma since the diseases often lack targetable mutations, says Rapisuwon. Data from the phase 3 CheckMate-067 trial demonstrated activity with ipilimumab (Yervoy) in combination with nivolumab (Opdivo) for patients with acral and mucosal melanoma. Although the efficacy was generally decreased in these subtypes compared with that in cutaneous melanoma, this is the preferred frontline regimen, Rapisuwon explains. 

Future research efforts are aiming to identify novel combinations to treat these patient populations, Rapisuwon says. For example, Chinese investigators are looking into combining PD-1 inhibitors with VEGF inhibitors, such as axitinib (Inlyta). The goal of combination therapy is to provide patients with additional benefit compared with PD-1 inhibitors alone, Rapisuwon explains. However, more data are needed to establish the utility of combination therapy and move forward with other clinical trials, concludes Rapisuwon.

Suthee Rapisuwon, MD, discusses the frontline treatment of acral and mucosal melanoma.  


Suthee Rapisuwon, MD

Articles

Dr. Rapisuwon on Clinical Trial Barriers in the United States in Mucosal Melanoma

Dr. Rapisuwon on the Potential Utility of Toripalimab in Melanoma Subtypes

Dr. Rapisuwon on Frontline Immunotherapy Vs Targeted Therapy in Melanoma Subtypes

Dr. Rapisuwon on Biologic Differences Between Mucosal and Cutaneous Melanoma

Dr. Rapisuwon on the Frontline Treatment of Acral and Mucosal Melanoma