Discussion
cancers, melanoma, cancer, melanoma cancer, breast, liver cancer, TRAEs
LIVER METASTASIS, CANCERS, CANCER, MELANOMA
In this study, Pucotenlimab achieved an ORR of 20.17% (24/119, 95% CI, 13.370%-28.506%) in ≥ second line setting, which was in line with the other anti-PD-1 products approved for advanced melanoma in a similar setting, among them were Pembrolizumab with an ORR of 16.7% (95% CI, 10.0%-25.3%) and Toripalimab with an ORR of 17.3% (95% CI, 11.2%–25.0%) [The patients in the current study achieved a median OS of 16.59 (95% CI, 13.963–26.973) months, which was significantly longer than those of the conventional therapies of approximately 8 months [In our study, the cutaneous subtype achieved the highest ORR among different known primary subtypes, followed by the acral, and then the mucosal subtype. The same patterns were observed in mPFS and mOS. Thus, ORR and PFS might be appropriate surrogate endpoints for OS, the gold-standard endpoint for efficacy in a similar setting.ADA post Pucotenlimab treatment was detected in 4 out of 119 (3.36%). No ADA-related AE or aggravation was observed in these ADA-positive patients. Two of them achieved SD as the best response to Pucotenlimab (data was not showed). Therefore, it seemed that the influence of ADAs in the current study was minimal.According to James C. Lee, et al., anti-P-1/PD-L1 therapy demonstrated low effectiveness for various cancers with liver metastasis including melanoma. The underlying mechanisms were CD8 + T cell depletion in liver and distal immunosuppression induced by regulatory T-cell activation [It was acknowledged that BRAF mutation did not affect the benefit melanoma patients got from anti-PD-1 treatment [In our study, the rates of TRAEs of any Grade and of Grade ≥ 3 were 77.3% and 15.1%, respectively, which were similar to those reported in Pembrolizumab of 84.5% and 8.7%, and Toripalimab of 90.6% and 19.6% in the same setting. Besides, no new types of TRAEs appeared in our study compared with Pembrolizumab and Toripalimab during long-term safety follow-up [In the current study, serum Eotaxin level during the treatment was positively correlated with PR status in patients treated with Pucotenlimab, which supported the efficacy-predicting role of Eotaxin and its effector cells eosinophil for anti-PD-1 treatment in various types of cancer including melanoma [A variety of cancers (lung, breast, liver cancer) highly expressed CCL2, and usually it was associated with poor prognosis. Besides, Megan M. Tu, et al. showed that the efficacy of anti-PD-1 therapy was boosted by inhibiting CCL2 receptor, CCR2 [Previous studies showed that TGF-α was upregulated in many types of cancers including melanoma. Its higher serum level was associated with poorer prognosis. The underlying mechanism was its pro-differentiation capability for melanoma cancer cells [Serum VEGF level has been suggested as a poor prognostic marker for Ipilimumab for the treatment of advanced melanoma, but not for PD-1 inhibitors or in combination with Ipilimumab [Due to the limited sample size in the current study, the conclusions drawn above may be inaccurate, which needs further investigation in future phase III study that has been approved by the Chinese National Medical Products Administration (NMPA) with a large sample size involved.