[A retrospective study of PD-1 monoclonal antibody combined with nab-paclitaxel plus bevacizumab in the treatment of advanced malignant melanoma].

Objective

Advanced malignant melanoma still poses significant challenges in treatment. Combining nab-paclitaxel, bevacizumab, and immunotherapy has shown promising efficacy across various cancer types. This retrospective study aimed to assess the efficacy and safety of this regimen in patients with advanced melanoma and explore related biomarkers.

Methods

Patients with histologically confirmed inoperable stage Ⅲ or Ⅳ melanoma and Eastern Cooperative Oncology Group Performance Status 0-2 were included in this retrospective study conducted from September 2020 to August 2023. Patients received combination therapy with nab-paclitaxel, bevacizumab, and toripalimab (Q3W) at Nanjing Drum Tower Hospital. Maintenance therapy with bevacizumab and toripalimab was given after 6-8 cycles without disease progression or intolerable adverse reactions. Personalized radiotherapy was delivered. The primary endpoint was the confirmed objective response rate (ORR) and disease control rate (DCR).

Results

As of January 20, 2024, 28 out of 41 patients showed tumor shrinkage, including 4.9% (n=2) achieving complete response (CR) and 63.4% (n=26) achieving partial response (PR). The confirmed ORR was 63.4% (95% CI: 46.9%-77.9%) and the DCR was 92.7% (95% CI: 80.1%-98.5%). The median PFS was 14.2 months, the 1-year survival rate was 75.5% (95% CI: 62.7%-90.9%), and the 2-year survival rate was 54.6% (95% CI: 38.1%-78.1%). Moreover, patients who received radiotherapy exhibited a longer median progression-free survival (mPFS) (14.3 months vs 7.0 months, HR=0.45 [95% CI: 0.20-1.01]). Grade 3 treatment-related adverse events were leukopenia, neutropenia, AST/ALT elevation, adrenal insufficiency, hypertriglyceridemia and neurotoxicity. No treatment-related deaths were observed. In addition, biomarker analysis showed that liver metastasis, MET mutation, and NF1 mutation were independent predictors of PFS (P=0.006, 0.038, and 0.002, respectively).

Conclusions

This study demonstrates that toripalimab, in combination with nab-paclitaxel and bevacizumab, offers a potential therapeutic option for advanced melanoma with acceptable toxicity. Furthermore, this triplet therapy combined with radiotherapy significantly improves PFS. Preliminary biomarker analysis suggests that patients with liver metastasis, MET or NF1 mutations may be less likely to benefit from this treatment regimen.