Background
PD-L1 expression (PD-L1) on tumor cells with or without immune cells is widely reported in clinical trials of PD-1 blockade in metastatic non-small cell lung cancer (NSCLC). Various cutpoints have been studied.
Methods
We performed a systematic search of MEDLINE, EMBASE and conference proceedings up to December 2019 for randomized and non-randomized clinical trials of anti-PD-1 or anti-PD-L1 monotherapy in metastatic NSCLC. We retrieved data on objective response rate (ORR), 1 year (1yr PFS) and 2 year progression-free survival (2yr PFS), and 2 year (2yr OS) and 3 year overall survival (3yr OS) in various PD-L1 subgroups. Results were pooled and analysed based on different cutpoints, with non-randomized comparisons made to pooled chemotherapy outcomes.
Results
9,810 patients in twenty-seven studies were included. In treatment-naïve patients, benefits with PD-1 blockade over chemotherapy were seen in ORR in patients having PD-L1 ≥50%, in 2yr OS for PDL1 ≥1%, and in 1yr PFS, 2yr PFS and 3yr OS for unselected patients. First-line PD-1 blockade compared to chemotherapy demonstrated higher ORR, 2yr PFS and 3yr OS if PD-L1 ≥50%; lower ORR, higher 2yr PFS and similar 3yr OS if PD-L1 1-49%; and lower ORR, similar 1yr PFS and lower 2yr OS if PD-L1 <1%. In previously treated patients, PD-1 blockade demonstrated similar or superior outcomes to chemotherapy in all PD-L1 subgroups.
Conclusions
PD-L1 should guide the choice of PD-1 blockade versus chemotherapy in treatment-naïve patients. In previously treated patients, PD-1 blockade provides a favourable outcome profile to chemotherapy in all PD-L1 subgroups.
Epithelial ovarian cancer (EOC) is the most important cause of gynecological cancer-related mortality. Despite improvements in medical therapies, particularly with the incorporation of drugs targeting homologous recombination deficiency, EOC survival rates remain low. Adoptive cell therapy (ACT) is a personalized form of immunotherapy in which autologous lymphocytes are expanded, manipulated ex vivo, and re-infused into patients to mediate cancer rejection. This highly promising novel approach with curative potential encompasses multiple strategies, including the adoptive transfer of tumor-infiltrating lymphocytes, natural killer cells, or engineered immune components such as chimeric antigen receptor (CAR) constructs and engineered T-cell receptors. Technical advances in genomics and immuno-engineering have made possible neoantigen-based ACT strategies, as well as CAR-T cells with increased cell persistence and intratumoral trafficking, which have the potential to broaden the opportunity for patients with EOC. Furthermore, dendritic cell-based immunotherapies have been tested in patients with EOC with modest but encouraging results, while the combination of DC-based vaccination as a priming modality for other cancer therapies has shown encouraging results. In this manuscript, we provide a clinically oriented historical overview of various forms of cell therapies for the treatment of EOC, with an emphasis on T-cell therapy.
Prostate cancer is the second most common cancer in men and represents a significant healthcare burden worldwide. Therapeutic options in the metastatic castration-resistant setting remain limited, despite advances in androgen deprivation therapy, precision medicine and targeted therapies. In this review, we summarize the role of immunotherapy in prostate cancer and offer perspectives on opportunities for future development, based on current knowledge of the immunosuppressive tumor microenvironment. Furthermore, we discuss the potential for synergistic therapeutic strategies with modern radiotherapy, through modulation of the tumor microenvironment. Emerging clinical and pre-clinical data suggest that radiation can convert immune desert tumors into an inflamed immunological hub, potentially sensitive to immunotherapy.
cases have been stained and reviewed (Table). The sensitivity and specificity was 71% and 100%, respectively. The PPV and NPV were 100% and 69%, respectively. We expect to complete our analysis of all patients prior to the IASLC World Conference. Conclusion: Positive PD-L1 IHC staining on EBUS-TBNA aspirates appears to have a strong correlation with resected tumor specimen. When EBUS-TBNA aspirates are negative for PD-L1 staining, additional tumor specimens are required to confirm the PD-L1 status.
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