Instructions for Pembrolizumab

1. Generic name: pembrolizumab

Product name:Keytruda

All names: Pembrolizumab, Pembrolizumab, Keytruda, Pembrolizumab, Jianxude

2. Indications:

1. Melanoma:

Pembrolizumab is used to treat patients with unresectable or metastatic melanoma, and also includes adjuvant therapy for adults and children (12 years and older) with stage IIB, IIC, or III melanoma after complete resection.

2. Non-small cell lung cancer (NSCLC):

(1) Pembrolizumab combined with pemetrexed and platinum-based chemotherapy is suitable for first-line treatment of patients with metastatic non-squamous non-small cell lung cancer without EGFR or ALK genomic tumor abnormalities.

(2) Pembrolizumab combined with carboplatin and paclitaxel or paclitaxel protein conjugate is suitable for first-line treatment of patients with metastatic squamous non-small cell lung cancer.

(3) As a single agent, pembrolizumab is indicated for the first-line treatment of patients with non-small cell lung cancer that expresses PD-L1 [Tumor Proportion Score (TPS) ≥1%], has no EGFR or ALK genomic tumor abnormalities, as determined by an FDA-approved trial, and whose cancer is stage III with fever and is not suitable for surgical resection or definitive chemoradiotherapy, or is metastatic.

(4) As a single agent, pembrolizumab is indicated for the treatment of patients with metastatic non-small cell lung cancer whose tumors express PD-L1 (TPS ≥ 1%) as determined by an FDA-approved trial and who have disease progression during or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor abnormalities should have disease progression on an FDA-approved treatment for these abnormalities before receiving pembrolizumab.

(5) As a single agent, pembrolizumab is indicated for the adjuvant treatment of adult patients with stage IB (T2a ≥ 4 cm), stage II or IIIA non-small cell lung cancer after resection and platinum-based chemotherapy.

3. Head and neck squamous cell carcinoma (HNSCC):

(1) Pembrolizumab (FU) combined with platinum and fluorouracil is suitable for the first-line treatment of patients with metastatic or unresectable recurrent head and neck squamous cell carcinoma.

(2) As a single agent, pembrolizumab is indicated for the first-line treatment of patients with metastatic or unresectable recurrent HNSCC whose tumors express PD-L1 [trial-determined composite positivity score (CPS) ≥1], and for the treatment of patients with recurrent or metastatic HNSCC who have experienced disease progression during or after platinum-containing chemotherapy.

4. Classic Hodgkin lymphoma (cHL):

Pembrolizumab is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma and for the treatment of pediatric patients with refractory cHL or cHL that has relapsed after 2 or more courses of therapy.

5. Primary large mediastinumB-cell lymphoma (PMBCL):

Pembrolizumab is indicated for the treatment of adult and pediatric patients with primary mediastinal large B-cell lymphoma that is refractory or has relapsed after 2 or more prior lines of therapy. However, it is not recommended for the treatment of PMBCL patients who require urgent cytoreductive therapy.

6. Urothelial carcinoma:

(1) The combination of pembrolizumab and ennosumab is suitable for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who are not suitable for cisplatin-containing chemotherapy.

(2) As a single agent, pembrolizumab is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma, including patients who are ineligible for any platinum-containing chemotherapy or who have disease progression during or after platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

(3) As a single agent, pembrolizumab is indicated for the treatment of patients with BCG-unresponsive, high-risk, non-muscle-invasive bladder cancer (NMIBC), carcinoma in situ (CIS), with or without papillary tumors, who are not suitable for or choose not to undergo cystectomy.

7. Microsatellite instability-high or mismatch repair deficient cancers:

Pembrolizumab is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors who have progressed after prior therapy and who have no satisfactory alternative treatment options, as determined by an FDA-approved trial.

8. Microsatellite instability-high or mismatch repair-deficient colorectal cancer (CRC):

Pembrolizumab is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer determined in an FDA-approved trial.

9. Gastric cancer: Pembrolizumab combined with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy is suitable for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

10. Esophageal cancer:

Pembrolizumab is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumor center 1 to 5 cm above the GEJ) cancer who are not candidates for surgical resection. or definitive chemoradiotherapy: may be used in combination with platinum- and fluoropyrimidine-based chemotherapy or as a single agent after one or more systemic therapies in patients with tumors with squamous cell histology determined by FDA-approved trials to express PD-L1 (CPS ≥ 10).

11. Cervical cancer:

Pembrolizumab is indicated for use in combination with chemotherapy, with or without bevacizumab, for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors have been determined to express PD-L1 (CPS ≥ 1) as determined by an FDA-approved trial.

As a single agent, pembrolizumab is indicated for the treatment of patients with recurrent or metastatic cervical cancer whose disease has progressed during or after chemotherapy and whose tumors express PD-L1 (CPS ≥ 1) as determined by an FDA-approved test

12. Hepatocellular carcinoma (HCC):

Pembrolizumab is indicated for patients with hepatocellular carcinoma who have been previously treated with sorafenib.

13. Merkel cell carcinoma (MCC):

Pembrolizumab is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastaticMerkel cell carcinoma.

14. Renal cell carcinoma (RCC):

Pembrolizumab combined with axitinib is suitable for the first-line treatment of adult patients with advanced renal cell carcinoma(RCC), and combined with lenvatinib is suitable for the first-line treatment of adult patients with advanced renal cell carcinoma. Also applicable to patients with moderate or high risk of recurrence after nephrectomy or nephrectomy and metastasis resectionAdjuvant therapy for patients with RCC.

15. Endometrial cancer

(1) Pembrolizumab in combination with lenvatinib is indicated for the treatment of patients with advanced endometrial cancer determined by FDA-approved trials to be mismatch repair proficient (pMMR) or non-MSI-H, who have disease progression after prior systemic therapy in any setting and are not candidates for curative surgery or radiation therapy.

(2)As a single agent, pembrolizumab is indicated for the treatment of patients with advanced endometrial cancer determined to be MSI-H or dMMR in an FDA-approved trial who have progressed on systemic therapy in any setting and are not candidates for curative surgery or radiation therapy.

16. Tumor mutation burden-High cancer:

Pembrolizumab is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutation burden-high (TMB-H) [≥10 mutations per megabase (mut/Mb)] solid tumors as determined byFDA-approved trials who have progressed after prior therapy and for whom satisfactory alternative treatment options are not available.

17. Cutaneous squamous cell carcinoma (cSCC):

Pembrolizumab is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma or locally advanced cSCC that cannot be cured by surgery or radiotherapycSCC.

18. Triple negative breast cancer (TNBC):

Pembrolizumab is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer as neoadjuvant therapy in combination with chemotherapy and then continued as a single agent as adjuvant therapy after surgery. Pembrolizumab is indicated in combination with chemotherapy for the treatment of patients with locally recurrent, unresectable, or metastatic TNBC whose tumors express PD-L1 (CPS ≥ 10) as determined by an FDA-approved test.

19. Adult classic Hodgkin lymphoma and adult primary mediastinal large B-cell lymphomaB-cell lymphoma: Pembrolizumab is suitable for adults with classic Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. The additional recommended dose is 400 mg every 6 weeks.

3. Usage and dosage:

The recommended dose of pembrolizumab in adults is 200 mg every three weeks or 400 mg every six weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. The pembrolizumab dose for children and adolescents is 2 mg/kg, up to a maximum of 200mg.

4. Adverse reactions:

Common side effects of pembrolizumab include fatigue, musculoskeletal pain, decreased appetite, itchy skin, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. People have had serious infusion-related reactions to pembrolizumab, as well as serious immune-related side effects, including inflammation of the lungs and endocrine organs, leading to inflammation of the pituitary gland, thyroid gland (hypothyroidism and hyperthyroidism), and pancreatitis, leading to type 1 diabetes and diabetic ketoacidosis, which has forced some people to undergo lifelong hormone therapy (insulin therapy or thyroid hormones).

5. Storage:

Store pembrolizumab vials in the original carton under refrigerated conditions2°C to 8°C (36°F to 46°F) to avoid light. Do not freeze. Don't shake.

6. Mechanism of action:

Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing the suppression of immune responses mediated by the PD-1 pathway, including anti-tumor immune responses. In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth.