This study, although conducted in melanoma, carries general implications. Immunotherapy has been an increasingly interesting breakthrough in the field of melanoma in recent years. The earliest breakthrough was the CTLA-4 monoclonal antibody Ipi, which prolonged overall survival in advanced melanoma; later, investigators demonstrated significant PD-1 antibody effects in patients who had failed ipilimumab (Ipi) therapy or had not received Ipi therapy (Ipi naive). The breakthrough points of this year’s ASCO annual meeting study were (1) the entry of PD-1 antibodies into first-line treatment of advanced melanoma with superior efficacy over CTLA-4 antibodies, and (2) the combination of Ipi with the PD-1 antibody NIVO, which was superior to monotherapy. This phase III clinical study yielded stunning results. The combination group had significantly better efficiency than Ipi alone, reaching 57.6%, PFS of 11.5 months, and overall survival not yet reached. It should be noted that in China, melanoma chemotherapy is only 7% effective with a PFS of 1.4 months. Very much looking forward to the overall survival results that may be presented at the ASCO annual meeting next year. I agree with the discussant. Based on the available evidence, either Nivolumab (NIVO) or Pembrolizumab (Pembro) should be pushed as first-line treatment for melanoma, and Ipi monotherapy for first-line treatment of advanced melanoma may be out of history. there is no final conclusion on NIVO versus Pembro, both are effective. Anti-PD-1 combined with Ipi therapy achieved higher response rates and longer PFS, especially for patients with PD-L1 positivity <5%, and the combination group was significantly higher than nivo, and of course nivo was higher than ipi. Based on this result, I personally feel that in the future, it may be sufficient for advanced melanoma treatment subgroups, PD-L1 high expression patients with NIVO or Pembro alone, in addition In terms of medical cost level, the single drug saves nearly 1/5 of the cost than the combination drug, and the efficacy is comparable; for patients with low PD-L1 expression, the efficacy of the combination group is significantly higher than that of the single drug group, so for patients with low PD-L1 expression, the combination drug is still promising. The two studies of NIVO combined with Ipi for melanoma in this annual meeting had serious toxicities, and the combination group was significantly higher than the single-agent group, with 55% of grade 3 to 4 toxicities and 36.4% of patients discontinuing the drug due to treatment-related side effects. Therefore, in the future, we need to focus on reducing side effects while ensuring the effect of combination drugs, using immunosuppressants or increasing the dosage of NIVO and Pembro, etc. The second direction is to find sensitive patients, and PD-L1 is still not the best biomarker to predict the efficacy of PD-1 antibody monotherapy or combination therapy, and a lot of basic research is needed in this area, and basic research is what we need to do. This is exactly the kind of work that needs to be done by our researchers. Also, an important implication of this study is that its results may influence the treatment of other tumors. Immunotherapy studies for lung cancer, breast cancer, colorectal cancer, and kidney cancer have all been conducted, and anti-CTLA-4 and anti-PD-1 treatments have been used successively for the treatment of patients other than melanoma, and some results have been achieved. On-site review by Professor Michael P. Atkins, Georgetown University NIVO and Pembro are two novel anti-PD-1 drugs, how should they be selected for clinical use? Based on the available clinical studies, there is no clear difference in efficacy or toxicity between the two in terms of usage, ORR, adverse effects, and survival data, so the decision depends to a greater extent on treatment plan, market, cost, experience of use, and biomarker prediction. In terms of toxicity, the NIVO+Ipi combination was significantly more toxic compared to single agents, but in a manageable range, without treatment-related deaths and without affecting the efficacy of drug use. In terms of efficacy, the following conclusions can be drawn: NIVO>Ipi, NIVO+Ipi>Ipi, and NIVO+Ipi may be greater than NIVO. PD-L1 is a relatively “weak” biomarker for predicting efficacy. On the one hand, PD-L1 measurement is complex, not ideal, and not comparable between methods, and on the other hand, PD-L1 expression is low, tumor heterogeneous, and easily induced. Indeed, in this study, PD-L1 expression was not examined in 2/3 of patients who were effective on NIVO monotherapy. Therefore, the use of PD-L1 as a biomarker in the clinic needs to be more standardized and refined, and it is too early to do so. In the absence of appropriate biomarkers, drug use may be based more on clinical experience, with NIVO+Ipi being considered for patients seeking efficacy while tolerating toxicity, and NIVO/Pembro monotherapy for patients who have difficulty tolerating toxicity. In addition, continued attention needs to be paid to potential biomarkers, such as CD8 T-cell and PD-L1 expression at the margin of tumor invasion, T-cell clones in tumors, and mutational burden. In conclusion, immunotherapy has become the new standard of care for advanced melanoma, and this study can demonstrate the superior efficacy of Nivo in combination with Ipi over Ipi alone, but biomarkers are not yet available for drug patient screening. A new standard of care for immunosuppressive drug combinations has been established, but more work is still needed.