PEMBROLIZUMAB - REVIEW OF USE AND EFFECTIVENESS IN THE TREATMENT OF SELECTED NEOPLASM

Keywords: Pembrolizumab, Cancer, Neoplasm, PD-1, PD-L1

Abstract

The growing number of oncological patients worldwide pushes the need to research new possibilities in cancer treatment. Cancer cells use various mechanisms to avoid destruction. One of them is the PD-1/PD-L1 pathway which is used by neoplasm cells to inhibit immune response from T-cells. Pembrolizumab, a monoclonal antibody, is targeted against PD-1 receptors, therefore enhances anti-cancer T-cell activity by disabling PD-1/PD-L1 interaction. This study summarizes the current state of knowledge on clinical usefulness and efficiency of pembrolizumab monotherapy, therapy combined with chemotherapy and perioperative use  in melanoma, non-small cell lung cancer, pleural mesothelioma, classic Hodgkin lymphoma, urothelial cancer, head and neck squamous cell carcinoma, renal cell carcinoma, high-level microsatellite instability (MSI-H) or demismatch repair deficiency (dMMR) neoplasm, esophageal cancer, triple negative breast cancer, endometrial cancer, cervical cancer, adenocarcinoma of the stomach or gastroesophageal junction and bile duct cancer. Patients who received pembrolizumab during clinical trials had longer median overall survival and progression free survival rates than patients in placebo groups. Higher expression levels of PD-L1 on tumor cells correlated with greater clinical response, however pembrolizumab therapy was also beneficial in patients with lower expression levels.

References

Kwok G, Yau TC, Chiu JW, Tse E, Kwong YL. Pembrolizumab (Keytruda). Hum Vaccin Immunother. 2016;12(11):2777-2789. doi:10.1080/21645515.2016.1199310

Liu J, Chen Z, Li Y, Zhao W, Wu J, Zhang Z. PD-1/PD-L1 Checkpoint Inhibitors in Tumor Immunotherapy. Front Pharmacol. 2021;12:731798. Published 2021 Sep 1. doi:10.3389/fphar.2021.731798

Centanni M, Moes DJAR, Trocóniz IF, Ciccolini J, van Hasselt JGC. Clinical Pharmacokinetics and Pharmacodynamics of Immune Checkpoint Inhibitors. Clin Pharmacokinet. 2019;58(7):835-857. doi:10.1007/s40262-019-00748-2

Hamid O, Robert C, Daud A, et al. Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Ann Oncol. 2019;30(4):582-588. doi:10.1093/annonc/mdz011

Long GV, Carlino MS, McNeil C, et al. Pembrolizumab versus ipilimumab for advanced melanoma: 10-year follow-up of the phase III KEYNOTE-006 study. Ann Oncol. 2024;35(12):1191-1199. doi:10.1016/j.annonc.2024.08.2330

Eggermont AM, Kicinski M, Blank CU, et al. Seven-year analysis of adjuvant pembrolizumab versus placebo in stage III melanoma in the EORTC1325 / KEYNOTE-054 trial. Eur J Cancer. 2024;211:114327. doi:10.1016/j.ejca.2024.114327

Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016;375(19):1823-1833. doi:10.1056/NEJMoa1606774

Mok TSK, Wu YL, Kudaba I, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019;393(10183):1819-1830. doi:10.1016/S0140-6736(18)32409-7

Wakelee H, Liberman M, Kato T, et al. Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer. N Engl J Med. 2023;389(6):491-503. doi:10.1056/NEJMoa2302983

Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378(22):2078-2092. doi:10.1056/NEJMoa1801005

Chu Q, Perrone F, Greillier L, et al. Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial. Lancet. 2023;402(10419):2295-2306. doi:10.1016/S0140-6736(23)01613-6

Kuruvilla J, Ramchandren R, Santoro A, et al. Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study. Lancet Oncol. 2021;22(4):512-524. doi:10.1016/S1470-2045(21)00005-X

Armand P, Zinzani PL, Lee HJ, et al. Five-year follow-up of KEYNOTE-087: pembrolizumab monotherapy for relapsed/refractory classical Hodgkin lymphoma. Blood. 2023;142(10):878-886. doi:10.1182/blood.2022019386

Balar AV, Castellano D, O'Donnell PH, et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2017;18(11):1483-1492. doi:10.1016/S1470-2045(17)30616-2

Fradet Y, Bellmunt J, Vaughn DJ, et al. Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up. Ann Oncol. 2019;30(6):970-976. doi:10.1093/annonc/mdz127

Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med. 2017;376(11):1015-1026. doi:10.1056/NEJMoa1613683

Apolo AB, Ballman KV, Sonpavde G, et al. Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma. N Engl J Med. 2025;392(1):45-55. doi:10.1056/NEJMoa2401726

Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394(10212):1915-1928. doi:10.1016/S0140-6736(19)32591-7

Uppaluri R, Haddad RI, Tao Y, et al. Neoadjuvant and Adjuvant Pembrolizumab in Locally Advanced Head and Neck Cancer. N Engl J Med. 2025;393(1):37-50. doi:10.1056/NEJMoa2415434

Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019;380(12):1116-1127. doi:10.1056/NEJMoa1816714

Choueiri TK, Tomczak P, Park SH, et al. Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma. N Engl J Med. 2024;390(15):1359-1371. doi:10.1056/NEJMoa2312695

Marabelle A, Le DT, Ascierto PA, et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2020;38(1):1-10. doi:10.1200/JCO.19.02105

Kojima T, Shah MA, Muro K, et al. Randomized Phase III KEYNOTE-181 Study of Pembrolizumab Versus Chemotherapy in Advanced Esophageal Cancer. J Clin Oncol. 2020;38(35):4138-4148. doi:10.1200/JCO.20.01888

Sun JM, Shen L, Shah MA, et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021;398(10302):759-771. doi:10.1016/S0140-6736(21)01234-4

Cortes J, Cescon DW, Rugo HS, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817-1828. doi:10.1016/S0140-6736(20)32531-9

Pusztai L, Denkert C, O'Shaughnessy J, et al. Event-free survival by residual cancer burden with pembrolizumab in early-stage TNBC: exploratory analysis from KEYNOTE-522. Ann Oncol. 2024;35(5):429-436. doi:10.1016/j.annonc.2024.02.002

Makker V, Colombo N, Casado Herráez A, et al. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. N Engl J Med. 2022;386(5):437-448. doi:10.1056/NEJMoa2108330

O'Malley DM, Bariani GM, Cassier PA, et al. Pembrolizumab in Patients With Microsatellite Instability-High Advanced Endometrial Cancer: Results From the KEYNOTE-158 Study. J Clin Oncol. 2022;40(7):752-761. doi:10.1200/JCO.21.01874

Colombo N, Dubot C, Lorusso D, et al. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021;385(20):1856-1867. doi:10.1056/NEJMoa2112435

Monk BJ, Colombo N, Tewari KS, et al. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023;41(36):5505-5511. doi:10.1200/JCO.23.00914

Lorusso D, Xiang Y, Hasegawa K, et al. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial. Lancet. 2024;403(10434):1341-1350. doi:10.1016/S0140-6736(24)00317-9

Rha SY, Oh DY, Yañez P, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2023;24(11):1181-1195. doi:10.1016/S1470-2045(23)00515-6

Janjigian YY, Kawazoe A, Bai Y, et al. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet. 2023;402(10418):2197-2208. doi:10.1016/S0140-6736(23)02033-0

Casak SJ, Kumar V, Song C, et al. FDA Approval Summary: Durvalumab and Pembrolizumab, Immune Checkpoint Inhibitors for the Treatment of Biliary Tract Cancer. Clin Cancer Res. 2024;30(16):3371-3377. doi:10.1158/1078-0432.CCR-24-0517

Park CS, Sung MJ, Kim SJ, et al. Prognostic Factors in Patients Treated with Pembrolizumab as a Second-Line Treatment for Advanced Biliary Tract Cancer. Cancers (Basel). 2022;14(17):4323. Published 2022 Sep 3. doi:10.3390/cancers14174323

Views:

12

Downloads:

8

Published
2025-12-29
Citations
How to Cite
Konrad Kulka, Wiktoria Król, Zuzanna Kafara, Donata Kowalczyk, Zuzanna Lechowska, Agnieszka Kafara, Rafał Szarek, Julia Koronczok-Matusiak, Katarzyna Michta, & Dominika Jurczak. (2025). PEMBROLIZUMAB - REVIEW OF USE AND EFFECTIVENESS IN THE TREATMENT OF SELECTED NEOPLASM. International Journal of Innovative Technologies in Social Science, 4(4(48). https://doi.org/10.31435/ijitss.4(48).2025.4453

Most read articles by the same author(s)