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Prognosis and Toxicity Stratified by Best Tumor Burden Change in Japanese Patients With Advanced Melanoma Treated
Ken Horisaki1,2, Shusuke Yoshikawa1, Wataru Omata1
1Department of Dermatology, Shizuoka Cancer Center, Shizuoka, Japan.
Abstract:
Immune checkpoint inhibitors (ICIs) have significantly improved outcomes in patients with advanced malignant melanoma (MM). However, more than half of patients receiving anti-programmed cell death protein-1 (PD-1) antibody monotherapy still fail to respond, with response rates varying by race and melanoma subtype. Additionally, immune-related adverse events (irAEs) remain a major concern. Although the best overall response based on Response Evaluation Criteria in Solid Tumors version 1.1 is commonly used in clinical trials to assess efficacy, its utility in predicting prognosis and toxicity in real-world clinical settings remains unclear. This retrospective cohort study conducted at Shizuoka Cancer Center in Japan evaluated the association between best tumor burden change (BTBC) in target lesions and prognosis or toxicity among Japanese patients with stage IV MM who received PD-1 monotherapy as first-line treatment. A total of 115 patients were analyzed. Prognosis improved proportionally with reductions in tumor burden from baseline. No significant difference was observed in overall survival between the partial response group and the stable disease group (p = 0.833). However, BTBC < 0% was a significant indicator of a favorable long-term prognosis (p < 0.001). The development of new lesions indicated poor prognosis; however, BTBC ≥ 0% represented poor prognosis regardless of new lesions. Regarding toxicity, the incidence of any-grade irAEs was significantly higher in the BTBC < 0% group than in the BTBC ≥ 0% group (p < 0.001), suggesting that greater tumor shrinkage correlated with increased toxicity. These findings indicate that BTBC may serve as a more accurate predictor of prognosis and toxicity than best overall response in clinical practice. Incorporating BTBC into treatment planning and toxicity monitoring could improve management of stage IV MM, though future prospective studies are needed to establish standardized BTBC criteria.
Insights
Best tumor burden change (BTBC) better predicts prognosis and toxicity in advanced malignant melanoma patients treated with anti-programmed cell death protein-1 (PD-1) therapy than overall response. Greater tumor shrinkage correlated with increased toxicity.
Area of Science:
- Oncology
- Immunotherapy
- Melanoma Research
Background:
- Immune checkpoint inhibitors (ICIs), particularly anti-programmed cell death protein-1 (PD-1) antibodies, have advanced treatment for advanced malignant melanoma (MM).
- However, a significant proportion of patients do not respond to PD-1 monotherapy, and response rates vary by patient demographics and melanoma subtype.
- Immune-related adverse events (irAEs) are a concern, and the utility of standard efficacy measures like best overall response in predicting real-world outcomes is unclear.
Purpose of the Study:
- To evaluate the association between best tumor burden change (BTBC) and prognosis or toxicity in Japanese patients with stage IV MM receiving first-line PD-1 monotherapy.
- To compare the predictive value of BTBC against best overall response for long-term outcomes and adverse events.
Main Methods:
- Retrospective cohort study at Shizuoka Cancer Center, Japan.
- Analysis of 115 patients with stage IV MM treated with first-line PD-1 monotherapy.
- Evaluation of the correlation between BTBC (percentage change in target lesion size) and overall survival, development of new lesions, and incidence of irAEs.
Main Results:
- Prognosis improved proportionally with tumor burden reduction; BTBC < 0% was a significant predictor of favorable long-term prognosis (p < 0.001).
- No significant difference in overall survival was found between partial response and stable disease groups (p = 0.833).
- Higher incidence of any-grade irAEs was observed in the BTBC < 0% group (p < 0.001), indicating greater tumor shrinkage correlated with increased toxicity.
Conclusions:
- Best tumor burden change (BTBC) may be a more accurate predictor of prognosis and toxicity in advanced MM patients treated with PD-1 monotherapy than best overall response.
- BTBC < 0% signifies a favorable prognosis, while BTBC ≥ 0% indicates poor prognosis irrespective of new lesion development.
- Incorporating BTBC into treatment planning and toxicity monitoring could enhance management strategies for stage IV MM, warranting prospective validation.
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