Difference between revisions of "Pembrolizumab (Keytruda)"

Revision as of 03:09, 11 June 2019

General information

Class/mechanism: PD-1 antibody. Pembrolizumab is a humanized monoclonal antibody which binds to the PD-1 receptor on T-cells. In some cancers, the PD-1 ligands are upregulated, which results in inhibition of T-cell immune surveillance of tumors. By blocking the interaction between the PD-1 receptor and its ligands PD-L1 and PD-L2, pembrolizumab decreases this immune system inhibition and facilitates anti-tumor immune response.^[1]^[2]^[3]
Route: IV
Extravasation: no information

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.^[1]

Diseases for which it is used

Patient drug information

Management checklist

CBC, comprehensive metabolic panel, Mg, Phos, LDH, TSH. Consider baseline EKG and troponin.

History of changes in FDA indication

Bladder cancer

5/18/2017: Regular approval for patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. (New disease indication)
5/18/2017: Accelerated approval for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.
6/19/2018: Label revised for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing therapy and whose tumors express PD-L1 (Combined Positive Score ≥ 10), or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.

Cervical cancer

6/12/2018: Approved for patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. (New disease indication)

Gastric or gastroesophageal junction adenocarcinoma

9/22/2017: Accelerated approval for patients with recurrent locally advanced or metastatic, gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 as determined by an FDA-approved test. Patients must have had disease progression on or after two or more prior systemic therapies, including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER2/neu-targeted therapy. (New disease indication)

Classical Hodgkin lymphoma (cHL)

3/14/2017: Accelerated approval for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or those who have relapsed after three or more prior lines of therapy. (New disease indication)

Head and neck squamous cell carcinoma

8/5/2016: Label expanded for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. (New disease indication)
6/10/2019: Approved for the first-line treatment of patients with metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) in combination with platinum and fluorouracil (FU) for all patients and as a single agent for patients whose tumors express PD‑L1 (Combined Positive Score [CPS] ≥1) (Approval extended to first-line setting)

Hepatocellular carcinoma

11/9/2018: Accelerated approval for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. (New disease indication)

Melanoma

9/4/2014: Initial accelerated FDA approval for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor.
12/18/2015: Label expanded for the treatment of patients with unresectable or metastatic melanoma. (Requirement for progression removed)
2/15/2019: Approved for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection. (Indication expanded to adjuvant setting)

Merkel cell carcinoma

12/19/2018: Approved for adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). (New disease indication)

MSI-H or dMMR tumors (tissue-agnostic)

5/23/2017: Granted FDA accelerated approval for adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options or with MSI-H or dMMR colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. (New disease-agnostic indication)

Non-small cell lung cancer

10/2/2015: Accelerated approval for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express programmed death ligand 1 (PD-L1) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab. (New disease indication)
10/24/2016: Label expanded for the following indications:
- Patients with metastatic NSCLC whose tumors have high PD-L1 expression (Tumor Proportion Score [TPS] greater than or equal to 50%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and no prior systemic chemotherapy treatment for metastatic NSCLC. (first-line indication with biomarker requirement)
- Patients with metastatic NSCLC whose tumors express PD-L1 (TPS greater than or equal to 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.
5/10/2017: FDA accelerated approval to be used in combination with pemetrexed and carboplatin for the treatment of patients with previously untreated metastatic non-squamous non-small cell lung cancer (NSCLC). (first-line indication with histology requirement)
8/20/2018: Granted regular approval in combination with pemetrexed and platinum as first-line treatment of patients with metastatic, non-squamous non-small cell lung cancer (NSqNSCLC), with no EGFR or ALK genomic tumor aberrations. (conversion to regular approval)
10/30/2018: Approval expanded in combination with carboplatin and either paclitaxel or nab-paclitaxel as first-line treatment of metastatic squamous non-small cell lung cancer (NSCLC). (first-line indication with histology requirement)
4/11/2019: Approval expanded for the first-line treatment of patients with stage III non-small cell lung cancer (NSCLC) who are not candidates for surgical resection or definitive chemoradiation or metastatic NSCLC. Patients’ tumors must have no EGFR or ALK genomic aberrations and express PD-L1 (Tumor Proportion Score [TPS] greater than or equal to 1%) (approval expanded to the non-metastatic setting)

Primary mediastinal B-cell lymphoma

6/13/2018: FDA approval expanded for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after two or more prior lines of therapy. (New disease indication)

Renal cell carcinoma

4/19/2019: FDA approved to be used together with axitinib for the first-line treatment of patients with advanced renal cell carcinoma (RCC). (New disease indication)

Also known as

Code names: MK-3475, SCH 900475
Generic names: lambrolizumab
Brand name: Keytruda

References

[insert-1] 1.0 ^1.1 ^1.2 Pembrolizumab (Keytruda) package insert

[2] Pembrolizumab (Keytruda) package insert (locally hosted backup)

[3] Keytruda manufacturer's website

[4] Pembrolizumab (Keytruda) patient drug information (Chemocare)

[5] Keytruda wallet card about side effects

[6] Pembrolizumab (Keytruda) patient drug information (UpToDate)

[1]

[2]

[3]

[4]

[5]

[6]

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 ==History of changes in FDA indication==
 ===[[Bladder cancer]]===
-*5/18/2017: [https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm559300.htm FDA regular approval] for "patients with locally advanced or metastatic [[Bladder cancer|urothelial carcinoma]] who have disease progression during or following [[:Category:Platinum_agents|platinum-containing]] chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with [[:Category:Platinum_agents|platinum-containing]] chemotherapy."
+*5/18/2017: [https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm559300.htm Regular approval] for patients with locally advanced or metastatic [[Bladder cancer|urothelial carcinoma]] who have disease progression during or following [[:Category:Platinum_agents|platinum-containing]] chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with [[:Category:Platinum_agents|platinum-containing]] chemotherapy. ''(New disease indication)''
-*5/18/2017: [https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm559300.htm Granted FDA accelerated approval] for "patients with locally advanced or metastatic [[Bladder cancer|urothelial carcinoma]] who are not eligible for [[Cisplatin (Platinol)|cisplatin-containing]] chemotherapy."
+*5/18/2017: [https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm559300.htm Accelerated approval] for patients with locally advanced or metastatic [[Bladder cancer|urothelial carcinoma]] who are not eligible for [[Cisplatin (Platinol)|cisplatin-containing]] chemotherapy.
-*6/19/2018: [https://www.fda.gov/drugs/resources-information-approved-drugs/fda-limits-use-tecentriq-and-keytruda-some-urothelial-cancer-patients FDA label revised] for the treatment of patients with locally advanced or metastatic [[bladder cancer|urothelial carcinoma]] who are not eligible for [[Cisplatin (Platinol)|cisplatin-containing]] therapy and whose tumors express PD-L1 (Combined Positive Score ≥ 10), or in patients who are not eligible for any [[:Category:Platinum_agents|platinum-containing]] chemotherapy regardless of PD-L1 status.
+*6/19/2018: [https://www.fda.gov/drugs/resources-information-approved-drugs/fda-limits-use-tecentriq-and-keytruda-some-urothelial-cancer-patients Label revised] for the treatment of patients with locally advanced or metastatic [[bladder cancer|urothelial carcinoma]] who are not eligible for [[Cisplatin (Platinol)|cisplatin-containing]] therapy and whose tumors express PD-L1 (Combined Positive Score ≥ 10), or in patients who are not eligible for any [[:Category:Platinum_agents|platinum-containing]] chemotherapy regardless of PD-L1 status.
 ===[[Cervical cancer]]===
-*6/12/2018: [https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-advanced-cervical-cancer-disease-progression-during-or-after-chemotherapy FDA approved] "for patients with recurrent or metastatic [[cervical cancer]] with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test."
+*6/12/2018: [https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-advanced-cervical-cancer-disease-progression-during-or-after-chemotherapy Approved] for patients with recurrent or metastatic [[cervical cancer]] with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. ''(New disease indication)''
 ===[[Gastric cancer|Gastric or gastroesophageal junction adenocarcinoma]]===
-*9/22/2017: [https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pembrolizumab-advanced-gastric-cancer FDA accelerated approval] "for patients with recurrent locally advanced or metastatic, [[Gastric cancer|gastric or gastroesophageal junction adenocarcinoma]] whose tumors express PD-L1 as determined by an FDA-approved test. Patients must have had disease progression on or after two or more prior systemic therapies, including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER2/neu-targeted therapy."
+*9/22/2017: [https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pembrolizumab-advanced-gastric-cancer Accelerated approval] for patients with recurrent locally advanced or metastatic, [[Gastric cancer|gastric or gastroesophageal junction adenocarcinoma]] whose tumors express PD-L1 as determined by an FDA-approved test. Patients must have had disease progression on or after two or more prior systemic therapies, including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER2/neu-targeted therapy. ''(New disease indication)''
 ===[[Hodgkin lymphoma|Classical Hodgkin lymphoma (cHL)]]===
-*3/14/2017: [https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm558604.htm Granted accelerated FDA approval] "for the treatment of adult and pediatric patients with refractory [[Hodgkin lymphoma|classical Hodgkin lymphoma (cHL)]], or those who have relapsed after three or more prior lines of therapy."
+*3/14/2017: [https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm558604.htm Accelerated approval] for the treatment of adult and pediatric patients with refractory [[Hodgkin lymphoma|classical Hodgkin lymphoma (cHL)]], or those who have relapsed after three or more prior lines of therapy. ''(New disease indication)''
 ===[[Head and neck cancer|Head and neck squamous cell carcinoma]]===
-*8/5/2016: [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm515627.htm Label expanded] for the treatment of patients with recurrent or metastatic [[Head and neck cancer|head and neck squamous cell carcinoma (HNSCC)]] with disease progression on or after [[:Category:Platinum_agents|platinum-containing]] chemotherapy. ''(New disease entity)''
+*8/5/2016: [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm515627.htm Label expanded] for the treatment of patients with recurrent or metastatic [[Head and neck cancer|head and neck squamous cell carcinoma (HNSCC)]] with disease progression on or after [[:Category:Platinum_agents|platinum-containing]] chemotherapy. ''(New disease indication)''
 *6/10/2019: Approved for the first-line treatment of patients with metastatic or unresectable recurrent [[Head and neck cancer|head and neck squamous cell carcinoma (HNSCC)]] in combination with platinum and fluorouracil (FU) for all patients and as a single agent for patients whose tumors express PD‑L1 (Combined Positive Score [CPS] ≥1) ''(Approval extended to first-line setting)''
 ===[[Hepatocellular carcinoma]]===
-*11/9/2018: [https://www.fda.gov/drugs/fda-grants-accelerated-approval-pembrolizumab-hepatocellular-carcinoma FDA accelerated approval] "for patients with [[Hepatocellular carcinoma|hepatocellular carcinoma (HCC)]] who have been previously treated with [[Sorafenib (Nexavar)|sorafenib]]."
+*11/9/2018: [https://www.fda.gov/drugs/fda-grants-accelerated-approval-pembrolizumab-hepatocellular-carcinoma Accelerated approval] for patients with [[Hepatocellular carcinoma|hepatocellular carcinoma (HCC)]] who have been previously treated with [[Sorafenib (Nexavar)|sorafenib]]. ''(New disease indication)''
 ===[[Melanoma]]===
 *9/4/2014: Initial [http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm412802.htm accelerated FDA approval] for the treatment of patients with unresectable or metastatic [[Melanoma|melanoma]] and disease progression following [[Ipilimumab (Yervoy)|ipilimumab]] and, if BRAF V600 mutation positive, a [[:Category:BRAF_inhibitors|BRAF inhibitor]].
-*12/18/2015: FDA label expanded for the treatment of patients with unresectable or metastatic [[Melanoma|melanoma]].
+*12/18/2015: Label expanded for the treatment of patients with unresectable or metastatic [[Melanoma|melanoma]]. ''(Requirement for progression removed)''
-*2/15/2019: [https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adjuvant-treatment-melanoma FDA approved] "for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection."
+*2/15/2019: [https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adjuvant-treatment-melanoma Approved] for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection. ''(Indication expanded to adjuvant setting)''
 ===[[Merkel cell carcinoma]]===
-*12/19/2018: [https://www.fda.gov/drugs/fda-approves-pembrolizumab-merkel-cell-carcinoma FDA approved] for adult and pediatric patients with recurrent locally advanced or metastatic [[Merkel cell carcinoma|Merkel cell carcinoma (MCC)]]. ''(New disease entity)''
+*12/19/2018: [https://www.fda.gov/drugs/fda-approves-pembrolizumab-merkel-cell-carcinoma Approved] for adult and pediatric patients with recurrent locally advanced or metastatic [[Merkel cell carcinoma|Merkel cell carcinoma (MCC)]]. ''(New disease indication)''
 ===[[MSI-H or dMMR|MSI-H or dMMR tumors (tissue-agnostic)]]===
-*5/23/2017: [https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm560040.htm Granted FDA accelerated approval] for "adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options or with MSI-H or dMMR [[Colon cancer|colorectal cancer]] that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan."
+*5/23/2017: [https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm560040.htm Granted FDA accelerated approval] for adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options or with MSI-H or dMMR [[Colon cancer|colorectal cancer]] that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. ''(New disease-agnostic indication)''
 ===[[Non-small cell lung cancer]]===
-*10/2/2015: [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm465650.htm Accelerated FDA approval] for the treatment of patients with metastatic [[Non-small_cell_lung_cancer|non-small cell lung cancer (NSCLC)]] whose tumors express programmed death ligand 1 (PD-L1) as determined by an FDA-approved test, with disease progression on or after [[:Category:Platinum_agents|platinum-containing]] chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.
+*10/2/2015: [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm465650.htm Accelerated approval] for the treatment of patients with metastatic [[Non-small_cell_lung_cancer|non-small cell lung cancer (NSCLC)]] whose tumors express programmed death ligand 1 (PD-L1) as determined by an FDA-approved test, with disease progression on or after [[:Category:Platinum_agents|platinum-containing]] chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab. ''(New disease indication)''
-*10/24/2016: [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm526430.htm FDA label expanded] for the following indications:
+*10/24/2016: [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm526430.htm Label expanded] for the following indications:
 **Patients with metastatic [[Non-small_cell_lung_cancer|NSCLC]] whose tumors have high PD-L1 expression (Tumor Proportion Score [TPS] greater than or equal to 50%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and no prior systemic chemotherapy treatment for metastatic NSCLC. (''first-line indication with biomarker requirement'')
 **Patients with metastatic [[Non-small_cell_lung_cancer|NSCLC]] whose tumors express PD-L1 (TPS greater than or equal to 1%) as determined by an FDA-approved test, with disease progression on or after [[:Category:Platinum_agents|platinum-containing]] chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.