The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
Pembrolizumab (Keytruda)
Open accessAbstract
The programmed cell death protein 1 (PD1) is one of the checkpoints that regulates the immune response. Ligation of PD1 with its ligands PDL1 and PDL2 results in transduction of negative signals to T-cells. PD1 expression is an important mechanism contributing to the exhausted effector T-cell phenotype. The expression of PD1 on effector T-cells and PDL1 on neoplastic cells enables tumor cells to evade anti-tumor immunity. Blockade of PD1 is an important immunotherapeutic strategy for cancers. Pembrolizumab (Keytruda) is a humanized monoclonal anti-PD1 antibody that has been extensively investigated in numerous malignancies. In melanoma refractory to targeted therapy, pembrolizumab induced overall response rates (ORRs) of 21-34%. It was superior to another immune checkpoint inhibitor ipilimumab (Yervoy) in stage III/IV unresectable melanoma. In refractory non-small cell lung cancer (NSCLC), pembrolizumab induced ORRs of 19-25%. Based on these results, pembrolizumab was approved by the USA FDA for the treatment of advanced melanoma and NSCLC. Tumor cell PDL1 expression may be a valid response predictor. Molecular analysis also showed that tumors with high gene mutation burdens, which might result in the formation of more tumor-related neo-antigens, had better responses to pembrolizumab. In malignancies including lymphomas and other solid tumors, preliminary data showed that ORRs of around 20-50 % could be achieved. Adverse events occurred in up to 60% of patients, but grade 3/4 toxicities were observed in <10% of cases. Immune-related adverse events including thyroid dysfunction, hepatitis and pneumonitis are more serious and may lead to cessation of treatment.
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Cites
Siegel, R. L., Miller, K. D., & Jemal, A. (2016) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21332 · Cited by 16,003
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency
Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., Skora, A. D., Luber, B. S., Azad, N. S., Laheru, D., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500596 · Cited by 9,377
Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer
Brahmer, J., Reckamp, K. L., Baas, P., Crinò, L., Eberhardt, W. E. E., Poddubskaya, E., Antonia, S., Pluzanski, A., Vokes, E. E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504627 · Cited by 8,447
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer
Brahmer, J. R., Tykodi, S. S., Chow, L. Q. M., Hwu, W.-J., Topalian, S. L., Hwu, P., Drake, C. G., Camacho, L. H., Kauh, J., Odunsi, K., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200694 · Cited by 7,945 · cited 1×
“Treatment with the anti-PDL1 antibody BMS-936559 in a variety of relapsed/refractory solid tumors yielded an overall response rate (ORR) of merely 6–17%.(28) In another clinical trial of the anti-PDL1 antibody MPDL3280A in patients with bladder cancer, the ORR varied from 11–43%.”
BackgroundMutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer
Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J. J., Lee, W., Yuan, J., Wong, P., Ho, T. S., et al. (2015) · Science · doi:10.1126/science.aaa1348 · Cited by 7,802
Herbst, R. S., Baas, P., Kim, D.-W., Felip, E., Pérez-Gracia, J. L., Han, J.-Y., Molina, J., Kim, J.-H., Arvis, C. D., Ahn, M.-J., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01281-7 · Cited by 6,449
Pembrolizumab for the Treatment of Non–Small-Cell Lung Cancer
Garon, E. B., Rizvi, N. A., Hui, R., Leighl, N., Balmanoukian, A. S., Eder, J. P., Patnaik, A., Aggarwal, C., Gubens, M., Horn, L., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1501824 · Cited by 6,198
Pembrolizumab versus Ipilimumab in Advanced Melanoma
Robert, C., Schachter, J., Long, G. V., Arance, A., Grob, J. J., Mortier, L., Daud, A., Carlino, M. S., McNeil, C., Lotem, M., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1503093 · Cited by 5,887
Cited by
Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4
Qin, S., Xu, L., Yi, M., Yu, S., Wu, K., & Luo, S. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1091-2 · Cited by 1,145
Mack, C. L., Adams, D., Assis, D. N., Kerkar, N., Manns, M. P., Mayo, M. J., Vierling, J. M., Alsawas, M., Murad, M. H., & Czaja, A. J. (2020) · Hepatology · doi:10.1002/hep.31065 · Cited by 983
Regulatory mechanisms of PD-1/PD-L1 in cancers
Lin, X., Kang, K., Chen, P., Zeng, Z., Li, G., Xiong, W., Yi, M., & Xiang, B. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02023-w · Cited by 784
Nanda, R., Liu, M. C., Yau, C., Shatsky, R., Pusztai, L., Wallace, A., Chien, A. J., Forero-Torres, A., Ellis, E., Han, H., et al. (2020) · JAMA Oncology · doi:10.1001/jamaoncol.2019.6650 · Cited by 710
Kwong, Y.-L., Chan, T. S. Y., Tan, D., Kim, S. J., Poon, L.-M., Mow, B., Khong, P.-L., Loong, F., Au-Yeung, R., Iqbal, J., et al. (2017) · Blood · doi:10.1182/blood-2016-12-756841 · Cited by 494
Self-citation
Metadata
- Authors
- Kwok, G., Yau, T. C. C., Chiu, J. W., Tse, E., & Kwong, Y.-L.
- Venue
- Human Vaccines & Immunotherapeutics
- Publisher
- Informa UK Limited
- Published
- 2016-07-11
- Volume
- 12
- Issue
- 11
- Pages
- 2777-2789
- ISSN
- 2164-5515 (ISSN-L)
- 2164-554X
- OpenAlex
- W4232349440
- Cited by
- 498
- References
- 25
- FWCI
- 4.64
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Kwok, G., Yau, T. C. C., Chiu, J. W., Tse, E., & Kwong, Y.-L. (2016). Pembrolizumab (Keytruda). Human Vaccines & Immunotherapeutics. https://doi.org/10.1080/21645515.2016.1199310
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
