Difference between revisions of "Pembrolizumab (Keytruda)"

Revision as of 20:39, 27 October 2021

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

Diseases for which it was used

Small cell lung cancer

Patient drug information

Management checklist

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

History of changes in FDA indication

Dosing

4/28/2020: FDA accelerated approval to a new "dosage of 400 mg every 6 weeks for all approved adult indications."

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; based on KEYNOTE-045)
5/18/2017: Accelerated approval for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy. (New disease indication; based on KEYNOTE-052)
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). (Biomarker restriction; based on KEYNOTE-361)
6/19/2018: Label revised for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. (Based on KEYNOTE-361)
1/8/2020: Approved for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy. (Based on KEYNOTE-057)

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; based on KEYNOTE-158)
10/13/2021: Approved in combination with chemotherapy, with or without bevacizumab, for patients with persistent, recurrent or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) (Based on KEYNOTE-826)

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; based on KEYNOTE-087)
10/15/2020: FDA extended approval for the treatment of: "adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL) and pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy." (Approval extended to third-line setting; based on KEYNOTE-204)

Colorectal cancer

5/23/2017: Granted FDA accelerated approval for adult and pediatric patients with MSI-H or dMMR colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. (New disease indication)
6/29/2020: Approved for the first-line treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer. (Converted to regular approval; expanded to first-line setting; based on KEYNOTE-177)

Cutaneous squamous cell carcinoma

6/24/2020: Approved for patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation. (New disease indication; based on KEYNOTE-629)

Endometrial cancer

9/17/2019: Accelerated approval in combination with Lenvatinib (Lenvima) for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) and who have disease progression following prior systemic therapy but are not candidates for curative surgery or radiation. (New disease indication; based on KEYNOTE-146)
7/21/2021: Full approval in combination with Lenvatinib (Lenvima) for patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation. (Based on KEYNOTE-775)

Esophageal cancer

7/30/2019: Approved for patients with recurrent, locally advanced or metastatic, squamous cell carcinoma of the esophagus (ESCC) whose tumors express PD-L1 (Combined Positive Score [CPS] ≥10), as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy. (New disease indication; based on KEYNOTE-180 and KEYNOTE-181)
3/22/2021: Approved in combination with platinum and fluoropyrimidine-based chemotherapy for patients with metastatic or locally advanced esophageal or gastroesophageal (GEJ) (tumors with epicenter 1 to 5 centimeters above the gastroesophageal junction) carcinoma who are not candidates for surgical resection or definitive chemoradiation. (Histology-specific restriction removed; protein expression requirement removed; prior therapy requirement removed; surgery and radiation eligibility restriction added; drug combination requirement added; based on KEYNOTE-590)

Gastric or gastroesophageal junction adenocarcinoma

5/5/2021: Granted accelerated approval in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. (Based on KEYNOTE-811)

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; based on KEYNOTE-012)
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; based on KEYNOTE-048)

Hepatocellular carcinoma

11/9/2018: Accelerated approval for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. (New disease indication; based on KEYNOTE-224)

Melanoma

9/4/2014: Initial accelerated FDA approval for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab (Based on KEYNOTE-002)
- 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; based on KEYNOTE-006)
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; based on KEYNOTE-054)

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; based on KEYNOTE-017)

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. (New disease-agnostic indication; based on KEYNOTE-016, KEYNOTE-164, KEYNOTE-012, KEYNOTE-028, and KEYNOTE-158)
6/16/2020: FDA accelerated approval "for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options." (based on KEYNOTE-158)

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. (New disease indication; based on KEYNOTE-010)
- Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.
10/24/2016: Label expanded for 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; based on KEYNOTE-024)
10/24/2016: Label expanded for 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. (Indication with biomarker requirement; based on KEYNOTE-042)
- 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; based on KEYNOTE-189)
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; based on KEYNOTE-407)
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; based on KEYNOTE-170)

Renal cell carcinoma

4/19/2019: Approved to be used together with Axitinib (Inlyta) for the first-line treatment of patients with advanced renal cell carcinoma (RCC). (New disease indication; based on KEYNOTE-426)
8/10/2021: Approved in combination with Lenvatinib (Lenvima) for first-line treatment of adult patients with advanced renal cell carcinoma (RCC). (Based on CLEAR)

TMB-H (tissue agnostic)

6/16/2020: Accelerated approval for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. (New disease-agnostic indication; based on KEYNOTE-158)

Triple-negative breast cancer (TNBC)

11/13/2020: Accelerated approval in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (CPS ≥10) as determined by an FDA approved test. (New disease indication; based on KEYNOTE-355)
7/26/2021: Regular approval for high-risk, early-stage, triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery. (Based on KEYNOTE-522)
7/26/2021: Regular approval in combination with chemotherapy for patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (Combined Positive Score [CPS] ≥10) as determined by an FDA approved test. (Based on KEYNOTE-522)

Withdrawn indications

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; based on KEYNOTE-059)
2022: Indication withdrawn by manufacturer.

Small cell lung cancer

6/17/2019: Accelerated approval for patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy. (New disease indication; based on KEYNOTE-028)
3/1/2021: Indication withdrawn by manufacturer.

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]

@@ Line 1: / Line 1: @@
 ==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.<ref name="insert">[http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf Pembrolizumab (Keytruda) package insert]</ref><ref>[[:File:Pembrolizumab.pdf | Pembrolizumab (Keytruda) package insert (locally hosted backup)]]</ref><ref>[http://www.keytruda.com/hcp/ Keytruda manufacturer's website]</ref>
+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.<ref name="insert">[http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf Pembrolizumab (Keytruda) package insert]</ref><ref>[[:File:Pembrolizumab.pdf | Pembrolizumab (Keytruda) package insert (locally hosted backup)]]</ref><ref>[http://www.keytruda.com/hcp/ Keytruda manufacturer's website]</ref>
 <br>Route: IV
 <br>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 [http://www.thomsonhc.com/home/dispatch Micromedex], [http://online.lexi.com/ Lexicomp], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.<ref name="insert"></ref>
 ==Diseases for which it is used==
 *[[Bladder cancer]]
 *[[Cervical cancer]]
@@ Line 27: / Line 25: @@
 *[[TMB-H|TMB-H solid tumors (tissue-agnostic)]]
 *[[Breast cancer, triple negative|Triple-negative breast cancer (TNBC)]]
 ==Diseases for which it was used==
 *[[Small cell lung cancer]]
 ==Patient drug information==
 *[http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf Pembrolizumab (Keytruda) package insert]<ref name="insert" />
 *[http://www.chemocare.com/chemotherapy/drug-info/Pembrolizumab.aspx Pembrolizumab (Keytruda) patient drug information (Chemocare)]<ref>[http://www.chemocare.com/chemotherapy/drug-info/Pembrolizumab.aspx Pembrolizumab (Keytruda) patient drug information (Chemocare)]</ref>
 *[https://www.keytruda.com/static/pdf/patient-wallet-card.pdf Keytruda wallet card about side effects]<ref>[https://www.keytruda.com/static/pdf/patient-wallet-card.pdf Keytruda wallet card about side effects]</ref>
 *[http://www.uptodate.com/contents/pembrolizumab-patient-drug-information Pembrolizumab (Keytruda) patient drug information (UpToDate)]<ref>[http://www.uptodate.com/contents/pembrolizumab-patient-drug-information Pembrolizumab (Keytruda) patient drug information (UpToDate)]</ref>
 ==[[Management checklist]]==
 *CBC, comprehensive metabolic panel, Mg, Phos, LDH, TSH. Consider baseline EKG and troponin.
 ==History of changes in FDA indication==
 ===Dosing===
 *4/28/2020: [https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-new-dosing-regimen-pembrolizumab FDA accelerated approval] to a new "dosage of 400 mg every 6 weeks for all approved adult indications."
 ===[[Bladder cancer]]===
 *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 [[Regimen_classes#Platinum-based_regimen|platinum-containing chemotherapy]] or within 12 months of neoadjuvant or adjuvant treatment with [[Regimen_classes#Platinum-based_regimen|platinum-containing chemotherapy]]. ''(New disease indication; based on KEYNOTE-045)''
 *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. ''(New disease indication; based on KEYNOTE-052)''
@@ Line 54: / Line 43: @@
 *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 any [[Regimen_classes#Platinum-based_regimen|platinum-containing chemotherapy]] regardless of PD-L1 status. ''(Based on KEYNOTE-361)''
 *1/8/2020: [https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-bcg-unresponsive-high-risk-non-muscle-invasive-bladder-cancer Approved] for the treatment of patients with [[Bacillus Calmette-Guérin (BCG)|Bacillus Calmette-Guerin (BCG)]]-unresponsive, high-risk, non-muscle invasive [[bladder cancer]] (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy. ''(Based on KEYNOTE-057)''
 ===[[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 Approved] for patients with recurrent or metastatic [[cervical cancer]] with disease progression on or after chemotherapy whose tumors [[Biomarkers#Expression|express]] [[Biomarkers#PD-L1|PD-L1]] (CPS ≥1) as determined by an FDA-approved test. ''(New disease indication; based on KEYNOTE-158)''
 *10/13/2021: Approved in combination with chemotherapy, with or without bevacizumab, for patients with persistent, recurrent or metastatic [[cervical cancer]] whose tumors [[Biomarkers#Expression|express]] [[Biomarkers#PD-L1|PD-L1]] (CPS ≥1) ''(Based on KEYNOTE-826)''
 ===[[Hodgkin lymphoma|Classical Hodgkin lymphoma (cHL)]]===
 *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; based on KEYNOTE-087)''
 *10/15/2020: [https://www.fda.gov/drugs/drug-approvals-and-databases/fda-extends-approval-pembrolizumab-classical-hodgkin-lymphoma FDA extended approval] for the treatment of: "adult patients with relapsed or refractory [[Hodgkin lymphoma|classical Hodgkin lymphoma (cHL)]] and pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy." ''(Approval extended to third-line setting; based on KEYNOTE-204)''
 ===[[:Category:Colorectal_cancers|Colorectal cancer]]===
 *5/23/2017: [https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm560040.htm Granted FDA accelerated approval] for adult and pediatric patients with [[Biomarkers#MSI-H|MSI-H]] or [[Biomarkers#dMMR|dMMR]] [[:Category:Colorectal_cancers|colorectal cancer]] that has progressed following treatment with a [[Regimen_classes#Fluoropyrimidine-based_regimen|fluoropyrimidine]], [[Regimen_classes#Oxaliplatin-based_regimen|oxaliplatin]], and [[Regimen_classes#Irinotecan-based_regimen|irinotecan]]. ''(New disease indication)''
 *6/29/2020: Approved for the first-line treatment of patients with unresectable or metastatic [[Biomarkers#MSI-H|microsatellite instability-high (MSI-H)]] or [[Biomarkers#dMMR|mismatch repair deficient (dMMR)]] [[:Category:Colorectal_cancers|colorectal cancer]]. ''(Converted to regular approval; expanded to first-line setting; based on KEYNOTE-177)''
 ===[[Cutaneous squamous cell carcinoma]]===
 *6/24/2020: Approved for patients with recurrent or metastatic [[Cutaneous squamous cell carcinoma|cutaneous squamous cell carcinoma (cSCC)]] that is not curable by surgery or radiation. ''(New disease indication; based on KEYNOTE-629)''
 ===[[Endometrial cancer]]===
 *9/17/2019: Accelerated approval in combination with [[Lenvatinib (Lenvima)]] for the treatment of patients with advanced [[Endometrial cancer|endometrial carcinoma]] that is not microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) and who have disease progression following prior systemic therapy but are not candidates for curative surgery or radiation. ''(New disease indication; based on KEYNOTE-146)''
 *7/21/2021: Full approval in combination with [[Lenvatinib (Lenvima)]] for patients with advanced [[Endometrial cancer|endometrial carcinoma]] that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation. ''(Based on KEYNOTE-775)''
 ===[[Esophageal cancer]]===
 *7/30/2019: Approved for patients with recurrent, locally advanced or metastatic, [[Esophageal squamous cell carcinoma|squamous cell carcinoma of the esophagus (ESCC)]] whose tumors [[Biomarkers#Expression|express]] [[Biomarkers#PD-L1|PD-L1]] (Combined Positive Score [CPS] ≥10), as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy. ''(New disease indication; based on KEYNOTE-180 and KEYNOTE-181)''
 *3/22/2021: Approved in combination with platinum and fluoropyrimidine-based chemotherapy for patients with metastatic or locally advanced [[Esophageal cancer|esophageal]] or gastroesophageal (GEJ) (tumors with epicenter 1 to 5 centimeters above the gastroesophageal junction) carcinoma who are not candidates for surgical resection or definitive chemoradiation. ''(Histology-specific restriction removed; protein expression requirement removed; prior therapy requirement removed; surgery and radiation eligibility restriction added; drug combination requirement added; based on KEYNOTE-590)''
 ===[[Gastric cancer|Gastric or gastroesophageal junction adenocarcinoma]]===
 *5/5/2021: Granted accelerated approval in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic [[Biomarkers#HER2|HER2]] [[Biomarkers#Overexpression|positive]] [[Gastric cancer|gastric]] or gastroesophageal junction (GEJ) adenocarcinoma. ''(Based on KEYNOTE-811)''
 ===[[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 [[Regimen_classes#Platinum-based_regimen|platinum-containing chemotherapy]]. ''(New disease indication; based on KEYNOTE-012)''
 *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 [[Biomarkers#Expression|express]] [[Biomarkers#PD-L1|PD‑L1]] (Combined Positive Score [CPS] ≥1) ''(Approval extended to first-line setting; based on KEYNOTE-048)''
 ===[[Hepatocellular carcinoma]]===
 *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; based on KEYNOTE-224)''
 ===[[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]] ''(Based on KEYNOTE-002)''
 **If [[Biomarkers#BRAF|BRAF]] [[Biomarkers#V600|V600 mutation positive]], a [[Regimen_classes#BRAF_TKI_therapy|BRAF inhibitor]].
 *12/18/2015: Label expanded for the treatment of patients with unresectable or metastatic [[Melanoma|melanoma]]. ''(Requirement for progression removed; based on KEYNOTE-006)''
 *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; based on KEYNOTE-054)''
 ===[[Merkel cell carcinoma]]===
 *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; based on KEYNOTE-017)''
 ===[[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, [[Biomarkers#MSI-H|microsatellite instability-high (MSI-H)]] or [[Biomarkers#dMMR|mismatch repair deficient (dMMR)]] [[:Category:Malignant solid neoplasm|solid tumors]] that have progressed following prior treatment and who have no satisfactory alternative treatment options. ''(New disease-agnostic indication; based on KEYNOTE-016, KEYNOTE-164, KEYNOTE-012, KEYNOTE-028, and KEYNOTE-158)''
+*6/16/2020: [https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors FDA accelerated approval] "for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options." (''based on KEYNOTE-158'')
 ===[[Non-small cell lung cancer]]===
 *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 [[Biomarkers#Expression|express]] [[Biomarkers#PD-L1|programmed death ligand 1 (PD-L1)]] as determined by an FDA-approved test, with disease progression on or after [[Regimen_classes#Platinum-based_regimen|platinum-containing chemotherapy]]. ''(New disease indication; based on KEYNOTE-010)''
 **Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.
@@ Line 123: / Line 87: @@
 *10/30/2018: Approval expanded in combination with carboplatin and either paclitaxel or nab-paclitaxel as first-line treatment of metastatic [[Non-small cell lung cancer, Squamous|squamous non-small cell lung cancer (NSCLC)]]. ''(First-line indication with histology requirement; based on KEYNOTE-407)''
 *4/11/2019: Approval expanded for the first-line treatment of patients with stage III [[Non-small_cell_lung_cancer|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 [[Biomarkers#Expression|express]] [[Biomarkers#PD-L1|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: [https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-treatment-relapsed-or-refractory-pmbcl FDA approval expanded] for the treatment of adult and pediatric patients with refractory [[Primary mediastinal B-cell lymphoma|primary mediastinal large B-cell lymphoma (PMBCL)]], or who have relapsed after two or more prior lines of therapy. ''(New disease indication; based on KEYNOTE-170)''
 ===[[Renal cell carcinoma]]===
 *4/19/2019: [https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-plus-axitinib-advanced-renal-cell-carcinoma Approved] to be used together with [[Axitinib (Inlyta)]] for the first-line treatment of patients with advanced [[Renal cell carcinoma|renal cell carcinoma (RCC)]]. ''(New disease indication; based on KEYNOTE-426)''
 *8/10/2021: Approved in combination with [[Lenvatinib (Lenvima)]] for first-line treatment of adult patients with advanced [[Renal cell carcinoma|renal cell carcinoma (RCC)]]. ''(Based on CLEAR)''
 ===[[TMB-H|TMB-H (tissue agnostic)]]===
 *6/16/2020: Accelerated approval for the treatment of adult and pediatric patients with unresectable or metastatic [[TMB-H|tumor mutational burden-high (TMB H)]] [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. ''(New disease-agnostic indication; based on KEYNOTE-158)''
 ===[[Breast cancer, triple negative|Triple-negative breast cancer (TNBC)]]===
 *11/13/2020: Accelerated approval in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic [[Breast cancer, triple negative|triple-negative breast cancer (TNBC)]] whose tumors [[Biomarkers#Expression|express]] [[Biomarkers#PD-L1|PD-L1]] (CPS ≥10) as determined by an FDA approved test. ''(New disease indication; based on KEYNOTE-355)''
 *7/26/2021: Regular approval for high-risk, early-stage, [[Breast cancer, triple negative|triple-negative breast cancer (TNBC)]] in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery. ''(Based on KEYNOTE-522)''
 *7/26/2021: Regular approval in combination with chemotherapy for patients with locally recurrent unresectable or metastatic [[Breast cancer, triple negative|TNBC]] whose tumors [[Biomarkers#Expression|express]] [[Biomarkers#PD-L1|PD-L1]] (Combined Positive Score [CPS] ≥10) as determined by an FDA approved test. ''(Based on KEYNOTE-522)''
 ==Withdrawn indications==
 ===[[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 Accelerated approval] for patients with recurrent locally advanced or metastatic, [[Gastric cancer|gastric]] or gastroesophageal junction adenocarcinoma whose tumors [[Biomarkers#Expression|express]] [[Biomarkers#PD-L1|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 [[Regimen_classes#Fluoropyrimidine-based_regimen|fluoropyrimidine-]] and [[Regimen_classes#Platinum-based_regimen|platinum-containing chemotherapy]] and, if appropriate, HER2/neu-targeted therapy. ''(New disease indication; based on KEYNOTE-059)''
 *2022: Indication withdrawn by manufacturer.
 ===[[Small cell lung cancer]]===
 *6/17/2019: Accelerated approval for patients with metastatic [[Small cell lung cancer|small cell lung cancer (SCLC)]] with disease progression on or after [[Regimen_classes#Platinum-based_regimen|platinum-based chemotherapy]] and at least one other prior line of therapy. ''(New disease indication; based on KEYNOTE-028)''
 *3/1/2021: Indication withdrawn by manufacturer.
 ==Also known as==
 *'''Code names:''' MK-3475, SCH 900475
 *'''Generic names:''' lambrolizumab
 *'''Brand name:''' Keytruda
 ==References==
 <references />
 [[Category:Drugs]]
 [[Category:Intravenous medications]]
 [[Category:Mutation-specific medications]]
 [[Category:Protein expression-specific medications]]
 [[Category:Anti-PD-1 antibodies]]
 [[Category:Bladder cancer medications]]
 [[Category:Breast cancer medications]]
@@ Line 180: / Line 127: @@
 [[Category:Hepatocellular carcinoma medications]]
 [[Category:Hodgkin lymphoma medications]]
 [[Category:Melanoma medications]]
 [[Category:Merkel cell carcinoma medications]]
 [[Category:MSI-H or dMMR medications]]
@@ Line 187: / Line 134: @@
 [[Category:Renal cell carcinoma medications]]
 [[Category:TMB-H medications]]
 [[Category:FDA approved in 2014]]
 [[Category:EMA approved drugs]]
 [[Category:PMDA approved drugs]]
 [[Category:WHO Essential Cancer Medicine]]
 [[Category:Merck product]]

Difference between revisions of "Pembrolizumab (Keytruda)"

Revision as of 20:39, 27 October 2021

Contents

General information

Diseases for which it is used

Diseases for which it was used

Patient drug information

Management checklist

History of changes in FDA indication

Dosing

Bladder cancer

Cervical cancer

Classical Hodgkin lymphoma (cHL)

Colorectal cancer

Cutaneous squamous cell carcinoma

Endometrial cancer

Esophageal cancer

Gastric or gastroesophageal junction adenocarcinoma

Head and neck squamous cell carcinoma

Hepatocellular carcinoma

Melanoma

Merkel cell carcinoma

MSI-H or dMMR tumors (tissue-agnostic)

Non-small cell lung cancer

Primary mediastinal B-cell lymphoma

Renal cell carcinoma

TMB-H (tissue agnostic)

Triple-negative breast cancer (TNBC)

Withdrawn indications

Gastric or gastroesophageal junction adenocarcinoma

Small cell lung cancer

Also known as

References

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