In 69 patients with lung cancer who developed COVID-19, disease severity and mortality were high, but prior PD-1 blockade was not a risk factor for poor outcomes in this group, suggesting the therapy should be used when indicated.

The utility of circulating tumor DNA (ctDNA) as a biomarker in patients with advanced cancers receiving immunotherapy is uncertain. We therefore analyzed pretreatment (n=978) and on-treatment (n=171) ctDNA samples across 16 advanced stage tumor types from three phase I/II trials of durvalumab (± anti-CTLA-4 therapy tremelimumab).Higher pretreatment variant allele frequencies (VAF) were associated with poorer overall survival and other known prognostic factors, but not objective response, suggesting a prognostic role for patient outcomes. On-treatment reductions in VAF and lower on-treatment VAF were independently associated with longer PFS and OS, and increased ORR, but not prognostic variables, suggesting that on-treatment ctDNA dynamics are predictive of benefit from immune checkpoint blockade. Accordingly, we propose a concept of "molecular response" using ctDNA, incorporating both pretreatment and on-treatment VAF that predicted long-term survival similarly to initial radiological response, while also permitting early differentiation of responders among patients with initially radiologically stable disease. SignificanceIn a pan-cancer analysis of immune checkpoint blockade, pretreatment ctDNA levels appeared prognostic and on-treatment dynamics predictive. A "molecular response" metric identified long-term responders and adjudicated benefit among patients with initial radiologically stable disease. Changes in ctDNA may be more dynamic than radiographic changes and could complement existing trial endpoints.

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Programmed cell death protein-1/ligand 1 (PD-1/L1) targeted immune checkpoint inhibitors have become the focus of tumor treatment due to their promising efficacy. Currently, several PD-1/PD-L1 inhibitors have been approved for clinical practice with several more in clinical trials. Notably, based on available trial data, the selection of different PD-1/PD-L1 inhibitors in the therapeutic application and the corresponding efficacy varies. Widespread attention then is increasingly raised to the clinical comparability of different PD-1/PD-L1 inhibitors. The comparison of the inhibitors could not only help clinicians make in-depth understanding of them, but also further facilitate the selection of the optimal inhibitor for patients in treatment as well as for future clinical research and the development of new related drugs. As we all know, molecular structure could determine molecular function, which further affects their application. Therefore, in this review, we aim to comprehensively compare the structural basis, molecular biological functions, and clinical practice of different PD-1/PD-L1 inhibitors.