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Neoadjuvant treatment with toripalimab and axitinib has demonstrated efficacy in a phase 2 trial of patients with resectable mucosal melanoma, according to researchers.
“Our study suggests that toripalimab plus axitinib may provide a promising new neoadjuvant treatment approach for patients with resectable mucosal melanoma,” the researchers wrote in Annals of Oncology.
This single-arm trial (ClinicalTrials.gov Identifier: NCT04180995) enrolled 29 patients with resectable mucosal melanoma. Their median age was 62 (range, 34-72) years, and 72.4% were women.
Nine patients had localized disease, 19 had regional lymph node disease, and 1 had oligometastasis of the left lung. Patients had tumors in the female genitourinary area (34.5%), ano-rectal area (34.5%), esophageal area (17.2%), and nasal/oral cavity (13.8%). Nine patients had genetic mutations, including c-KIT (n=4), NRAS (n=3), and BRAF (n=2) mutations.
All patients received 4 cycles of toripalimab (3 mg/kg every 2 weeks) and axitinib (5 mg twice daily) for 8 weeks. After completing this treatment, 24 of the 29 patients underwent surgery and received adjuvant treatment with toripalimab (3 mg/kg every 2 weeks) for up to 44 weeks. Six patients completed study treatment as planned.
The median follow-up was 34.2 months. The pathologic response rate was 33.3%, with 4 patients achieving a pathologic complete response.
By the data cutoff, all 24 evaluable patients had disease recurrence. Twenty-one had distant metastasis, and 3 had locoregional recurrence.
The median recurrence-free survival was 9.5 months, and the median event-free survival was 11.1 months. The median overall survival was not reached, but 5 patients died from melanoma.
The treatment was considered well-tolerated, as most treatment-related adverse events (TRAEs) were grade 1 or 2. All 29 patients had TRAEs, 27.5% had grade 3-4 TRAEs, and there were no fatal TRAEs.
The most common TRAEs were arrhythmias (58.6%), increased alanine aminotransferase (51.7%), increased aspartate aminotransferase (51.7%), dyslipidemia (41.4%), hypertension (41.4%), and hypothyroidism (41.4%).
The researchers also analyzed 17 paired formalin-fixed paraffin-embedded samples obtained at baseline and from the surgical specimen to evaluate the effects of neoadjuvant treatment on the immune microenvironment. The samples came from 5 patients who achieved a pathologic response and 12 who did not.
All evaluable patients had a significant increase in CD3+ tumor-infiltrating lymphocytes (TILs; P =.0032) and CD3+/CD8+ TILs (P =.0038) after neoadjuvant treatment. However, responders had a greater increase in CD3+ TILs (P =.027), CD3+/CD8+ TILs (P =.0039), and CD20+ TILs (P =.014) than nonresponders.
“[N]eoadjuvant treatment with toripalimab plus axitinib in resectable mucosal melanoma was well-tolerated and showed a promising pathological response rate,” the researchers wrote. “Importantly, infiltration of CD3+/CD8+ T cells after neoadjuvant therapy was associated with pathologic response.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Lian B, Li Z, Wu N, et al. Phase II clinical trial of neoadjuvant anti-PD-1 (toripalimab) combined with axitinib in resectable mucosal melanoma. Annals Oncol. Published online November 11, 2023. doi:10.1016/j.annonc.2023.10.793
This article originally appeared on Cancer Therapy Advisor
