pembrolizumab (Keytruda)
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Introduction
FDA-approved Sept. 2014
Indications
- cutaneous melanoma
- stage 3 cutaneous melanoma[8]
- treatment of cutaneous melanoma BRAF V600 mutation positive with or without previous treatment with ipilimumab (NICE)[1]
- treatment of metastatic non-small cell lung carcinoma (NSCLC) regardless of programmed death ligand 1 (PD-L1) expression on tumor cells[2]
- treatment of metastatic head & neck squamous cell carcinoma (HNSCC) or recurrent HNSCC with with disease progression on or after platinum-containing chemotherapy[3]
- advanced urothelial carcinoma that has failed platinum-based chemotherapy[3][7]
- treatment of any unresectable or metastatic solid tumor with microsatellite instability or mismatch repair deficiency[4]
- PD-L1 positive advanced esophageal cancer[6]
- partial response in 30% of patients
- PD-L1 positive advanced esophageal cancer[6]
- triple-negative breast cancer (HER2-, ER-, PR-) in combination with niraparib[11]
- niraparib + pembrolizumab may elicit a durable response in refractory (platinum-resistant) ovarian cancer[11]
- cervical cancer, gastric cancer, hepatocellular carcinoma,
- Hodgkin's lymphoma, diffuse large B-cell lymphoma[13]
- Merkel cell carcinoma (FDA-approved)
- recurrent or metastatic cutaneous squamous cell carcinoma (FDA-approved)[14]
Contraindications
- not approved for treatment of multiple myeloma[5]
Dosage
- 10 mg/kg every 2 or 3 weeks (cutaneous melanoma)[1]
- 200 mg every 3 weeks (NSCLC)[2]
- up to 1 year duration for adjuvant chemotherapy after surgical resection of stage 3 cutaneous melanoma[10]
- 35 cycles every 3 weeks ~ 2 years (NSCLC)
- q6weeks infusion frequency approved (NSCLC)
Adverse effects
- pneumonitis, hypothyroidism, arthralgia, vitiligo common with PD-1 inhibitors[13]
- immune-mediated colitis, autoimmune hepatitis
- drug adverse effects of checkpoint inhibitor(s)
- drug adverse effects of pharmaceutical monoclonal antibodies
Mechanism of action
- blocks ligand activation of programmed cell death-1 receptor (PD-1 receptor) on activated T cells (PD-L1 inhibitor)
Notes
- cost ~ $150,000/year (2014)
More general terms
References
- ↑ 1.0 1.1 1.2 Robert C, Schachter J, Long GV et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015 Apr 19; [e-pub] <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25891173 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1503093
Postow MA et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med 2015 Apr 20 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25891304 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1414428 - ↑ 2.0 2.1 2.2 Chustecka Z Earthquake in Lung Cancer: Immunotherapy First-Line. Medscape. Oct 14, 2016. http://www.medscape.com/viewarticle/870289
Reck M, Rodriguez-Abreu D, Robinson AG et al Pembrolizumab versus Chemotherapy for PD-L1-positive non-Small-Cell Lung Cancer. N Engl J Med. Oct 9, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27718847 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1606774
Elia J, Fairchild DG, Di Francesco L FDA Approves Pembrolizumab for Non-Small-Cell Lung Cancer Physician's First Watch, Oct 26, 2016 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
US Food and Drug Administration. October 2, 2015. FDA approves Keytruda for advanced non-small cell lung cancer. First drug approved in lung cancer patients whose tumors express PD-L1. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm465444.htm
Phull H 'Exciting But Very Real Possibility of Metastatic NSCLC Becoming a Chronic Illness' Impressive 5-year OS outcomes in this study certainly point to promising forecast. MedPage Today. ASCO Reading Room. August 6, 2021 https://www.medpagetoday.com/reading-room/asco/lung-cancer/93925
Pal S Keytruda in Advanced NSCLC -- Still on Target for Upping Long-Term Survival. Clinically meaningful 5-year results from the KEYNOTE-024 trial. MedPage Today. ASCO Reading Room. August 6, 2021 https://www.medpagetoday.com/asco/lung-cancer/93926 - ↑ 3.0 3.1 3.2 Bellmunt A, de Wit R, Vaughn DJ et al Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med 2017; 376:1015-1026. March 16, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28212060 Free full text <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1613683
- ↑ 4.0 4.1 Bankhead C FDA Breaks New Ground with Expanded Keytruda Indication - Pembrolizumab for genetic defect, not tumor type. MedPage Today. May 23, 2017 https://www.medpagetoday.com/PublicHealthPolicy/FDAGeneral/65530
FDA News Release. May 23, 2017 FDA approves first cancer treatment for any solid tumor with a specific genetic feature. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm560167.htm
Lemery S, Keegan P, Pazdur R First FDA Approval Agnostic of Cancer Site - When a Biomarker Defines the Indication. N Engl J Med 2017; 377:1409-1412. October 12, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29020592 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMp1709968 - ↑ 5.0 5.1 FDA Safety Alert. Aug 31, 2017 Keytruda (pembrolizumab) in Patients with Multiple Myeloma: FDA Statement - Two Clinical Trials on Hold. https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm574347.htm
- ↑ 6.0 6.1 George J, Pembrolizumab Promising in Advanced Esophageal Cancer. 30% of PD-L1-positive patients achieve partial response in small study. MedPage Today. January 07, 2018 https://www.medpagetoday.com/hematologyoncology/othercancers/70332
- ↑ 7.0 7.1 Bankhead C Survival Bump in Bladder Cancer with Keytruda. But no outcome advantage for Tecentriq in metastatic urothelial cancer. MedPage Today. Feb 11, 2018 https://www.medpagetoday.com/meetingcoverage/mgucs/71089
Bellmunt J et al Two-year follow-up from the phase III KEYNOTE 045 trial of pembrolizumab vs investigators choice in recurrent, advanced urothelial cancer. Genitourinary Cancers Symposium (GUCS) 2018; Abstract 410. - ↑ 8.0 8.1 8.2 8.3 Castellino AM Adjuvant Pembrolizumab for Melanoma -- Approval Imminent? Medscape - Apr 16, 2018. https://www.medscape.com/viewarticle/895204
- ↑ HIGHLIGHTS OF KEYTRUDA PRESCRIBING INFORMATION. Oct 2016 http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125514s012lbl.pdf
- ↑ 10.0 10.1 Eggermont AMM et al Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma. N Engl J Med 2018; 378:1789-1801. May 10, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29658430 Free full text https://www.nejm.org/doi/full/10.1056/NEJMoa1802357
- ↑ 11.0 11.1 11.2 Fuerst ML with expert critique by Sumrall AL Advanced TNBC: 'Durable Activity' for Niraparib + Pembrolizumab. Also benefit for platinum-resistant/refractory ovarian cancer. MedPage Today. ASCO Reading Room 06.21.2018 https://www.medpagetoday.com/reading-room/asco/immunotherapy/73611
- ↑ Kuznar W with critique by Hermel D Pembrolizumab Approved in Merkel Cell Carcinoma: Higher Response Rates, Less Toxicity Compared With Chemotherapy. Accelerated approval for both adults and children with recurrent locally advanced or metastatic disease. MedPage Today. ASCO Reading Room 01.26.2019 https://www.medpagetoday.com/reading-room/asco/skin-cancer/77620
- ↑ 13.0 13.1 13.2 Marin-Acevedo JA, Chirila RM, Dronca RS. Immune Checkpoint Inhibitor Toxicities. Mayo Clinic Proc. July 2019. 94(7):1321-1329 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31272574
- ↑ 14.0 14.1 Worcester S Latest FDA Pembrolizumab Approval Expands Label to Cutaneous SCCs. Medscape - Jul 13, 2021 https://www.medscape.com/viewarticle/954715