Pembrolizumab (Keytruda)

How is this drug name pronounced?

Pembrolizumab: pem-broh-LIH-zoo-mab

Keytruda: kee-TROO-duh


What cancer(s) does this drug treat?

Keytruda has been approved for a number of cancer types and stages, in some cases as a single therapy, and in some cases in combination with another therapy.

Keytruda is approved for:

Melanoma
Non-small cell lung cancer
Small cell lung cancer
Head and neck squamous cell cancer
Classical Hodgkin lymphoma
Primary mediastinal B cell lymphoma
Bladder and urinary tract (urothelial cell) cancer
Microsatellite instability-high cancer
Stomach cancer
Esophagus cancer
Cervical cancer
Liver cancer
Merkel cell carcinoma
Kidney cancer
Endometrial carcinoma

Advanced melanoma

Keytruda is approved for:

  • Patients with advanced melanoma that is metastatic (cancer has spread from the original cancer site to other parts of the body) or cannot be completely removed by surgery.
  • Patients with melanoma that, together with the lymph nodes that contain cancer, was completely removed by surgery. In such cases, Keytruda is used to help keep melanoma from coming back.

Advanced non-small cell lung cancer

Keytruda is approved for:

  • Patients with nonsquamous non-small cell lung cancer that has spread and does not have an abnormal EGFR or ALK gene. In such cases, Keytruda may be used in combination with the chemotherapy drug pemetrexed (Alimta) and a platinum chemotherapy as a first treatment.
  • Patients with squamous non-small cell lung cancer that has spread. In such cases, Keytruda may be used in combination with the chemotherapies carboplatin (Paraplatin) and paclitaxel (Taxol or Onxal) as a first treatment.
  • Patients with non-small cell lung cancer that:

    • tests positive for the PD-L1 molecule, AND
    • does not have an abnormal EGFR or ALK gene, AND
    • either has not spread outside the chest (stage III) but cannot be treated with surgery or chemotherapy with radiation, or has spread outside the chest.

In such cases, Keytruda may be used alone as a first treatment.

  • Patients with non-small cell lung cancer that tests positive for the PD-L1 molecule and has spread. The patient must have already tried chemotherapy containing platinum and it either did not work or stopped working. If the patient’s tumor has an abnormal EGFR or ALK gene, the patient has to have also tried an FDA-approved therapy for tumors with such abnormal genes prior to receiving Keytruda.

Advanced small cell lung cancer

Keytruda is approved for:

  • Patients with small cell lung cancer that has come back or spread after treatment with at least two different types of therapies, including chemotherapy containing platinum.

Head and neck squamous cell cancer

Keytruda is approved for:

  • Patients with head and neck squamous cell cancer that has spread or come back, cannot be removed by surgery, and tests positive for the PD-L1 molecule. In such cases, Keytruda may be used alone as a first treatment.
  • Patients with head and neck squamous cell carcinoma whose cancer has spread or come back after treatment with chemotherapy that contains platinum.
  • Patients with head and neck squamous cell cancer that has spread or come back and cannot be removed by surgery. In such cases, Keytruda may be used in combination with the chemotherapy drug fluorouracil (Adrucil) and a chemotherapy containing platinum as a first treatment.

Classical Hodgkin lymphoma

Keytruda is approved for:

  • Adult and pediatric patients with classical Hodgkin lymphoma that either has not responded to treatment, or has gotten better, but has then come back after three or more types of treatment.

Primary mediastinal B cell lymphoma

Keytruda is approved for:

  • Adult and pediatric patients with primary mediastinal B cell lymphoma that either has not responded to treatment, or has gotten better but then came back after two or more types of treatment. Keytruda is NOT recommended for patients with primary mediastinal B cell lymphoma who require urgent cytoreductive therapy to control the blood cell count.

Bladder and urinary tract (urothelial cell) cancer

Keytruda is approved for:

  • Patients with advanced urothelial carcinoma (the most common type of bladder and urinary tract cancer) that has grown or spread and cannot be removed by surgery:

    • who have been treated with chemotherapy containing platinum, and it did not work or stopped working, OR
    • whose cancer tests positive for the PD-L1 molecule and who cannot be treated with a chemotherapy containing cisplatin, OR
    • who cannot be treated with any chemotherapy containing platinum.
  • Patients with bladder cancer that has not yet spread to nearby tissue (called carcinoma in situ), but is at a high risk for spreading (high-risk, non-muscle invasive bladder cancer):

    • who have tried Bacillus Calmette-Guerin treatment, and it either did not work or stopped working, AND
    • who either cannot or choose not to have their bladder surgically removed.

Microsatellite instability-high cancer

Keytruda is approved for:

  • Adult and pediatric patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors whose cancer has spread or cannot be removed by surgery AND:

    • whose cancer responded to treatment, but then came back or got worse, and there are no satisfactory treatment options available, OR
    • who have colon or rectal cancer and have been treated with a fluoropyrimidine, oxaliplatin, and irinotecan, and the treatment did not work or stopped working.

Advanced stomach cancer

Keytruda is approved for:

  • Patients with a type of stomach cancer called gastric or gastroesophageal junction adenocarcinoma that has grown or spread and tests positive for the PD-L1 molecule, and who have been treated with at least two types of chemotherapy, including fluoropyrimidine and chemotherapy containing platinum, and it did not work or stopped working. If the patient has a cancer with an abnormal HER2/neu gene, the patient also has to have received a medicine targeting HER2/neu, and it either did not work or stopped working.

Advanced esophagus cancer

Keytruda is approved for:

  • Patients with esophageal squamous cell carcinoma that has come back or spread and that tests positive for the PD-L1 molecule, and who have received at least one treatment that either did not work or stopped working.

Advanced cervical cancer

Keytruda is approved for:

  • Patients with cervical cancer that has come back or spread or cannot be removed by surgery and tests positive for the PD-L1 molecule, and who have received chemotherapy that either did not work or stopped working.

Advanced liver cancer

Keytruda is approved for:

  • Patients with hepatocellular carcinoma (liver cancer) who have been treated with sorafenib (Nexavar).

Advanced Merkel cell carcinoma

Keytruda is approved for:

  • Adult and pediatric patients with Merkel cell carcinoma (a type of skin cancer) that has come back or spread.

Advanced kidney cancer

Keytruda is approved for:

  • Patients with renal cell carcinoma (kidney cancer) that has spread or cannot be removed by surgery. In such cases, Keytruda may be used in combination with Inlyta (axitinib) as a first treatment.

Advanced endometrial carcinoma

Keytruda is approved for:

Limitations of Use

Age: The safety and efficacy of Keytruda has been established in pediatric patients with classical Hodgkin lymphoma, primary mediastinal B cell lymphoma, microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) cancers, and Merkel cell carcinoma. The safety and efficacy of Keytruda in pediatric patients with MSI-H central nervous system cancers have not been established. The safety and efficacy of Keytruda in pediatric patients with all other cancer types approved for treatment with Keytruda have not been established.
Pregnancy/Breastfeeding: Keytruda can cause harm to a fetus, and is not recommended for use during pregnancy. The risks associated with Keytruda during breastfeeding are not known and cannot be ruled out; due to the potential for serious adverse reactions in the breastfed child, women are advised not to breastfeed during treatment and for 4 months after the last dose of Keytruda.


What type of immunotherapy is this?

Checkpoint Blockade

  • PD-1 blockade

How does this drug work?

  • Target: PD-1

Keytruda is an antibody that attaches to a molecule called PD-1, which is present on the surface of T cells – the primary immune cells involved in killing cancer cells. In healthy tissues, PD-1 acts as a brake that keeps T cells from creating an immune reaction that gets out of control. However, cancers can hijack this safety mechanism and prevent T cells from doing their job – killing the cancer cells. This can happen when cancer cells or other cells within the tumor mass display molecules called PD-L1 or PD-L2 on their surface. When PD-L1 or PD-L2 interact with PD-1 on T cells, the T cells become inactive and do not attack the cancer cells. Keytruda binds to the PD-1 molecules on T cells in such a way that it prevents the interaction between PD-1 and PD-L1/PD-L2 and allows the T cells to be active and attack the cancer cells.

Illustration that shows how Keytruda works


How is this drug given to the patient?

Keytruda is administered via a tube into a vein (intravenous infusion, or I.V.) over 30 minutes every three weeks.


What are the observed clinical results?

For:

Advanced melanoma (metastatic or not removable by surgery)
Advanced melanoma (completely removed by surgery)
Advanced non-small cell lung cancer (squamous and non-squamous)
Advanced small cell lung cancer
Head and neck squamous cell cancer
Classical Hodgkin lymphoma
Primary mediastinal B cell lymphoma
Bladder and urinary tract (urothelial cell) cancer
Microsatellite instability-high cancer
Advanced stomach cancer
Advanced esophagus cancer
Advanced cervical cancer
Advanced liver cancer
Advanced Merkel cell carcinoma
Advanced kidney cancer
Advanced endometrial carcinoma

It is important to keep in mind that each patient’s actual outcome is individual and may be different from the results found in the clinical studies. In addition, with immunotherapy, sometimes it takes several months for responses to be observed. The long-term clinical trial data currently available is limited, and more clinical trials are ongoing.

Advanced melanoma (metastatic or not removable by surgery)

In a clinical trial, 834 patients with unresectable or metastatic melanoma and no prior ipilimumab treatment received either Keytruda or Yervoy (ipilimumab – another form of immunotherapy). At a median follow-up of 23 months:

Advanced melanoma metastatic fig 1 (diagram)

In another clinical trial, 540 patients with unresectable or metastatic melanoma that did not respond to or progressed on Yervoy (ipilimumab) received either Keytruda or chemotherapy. At a median follow-up of 18 months:

Advanced melanoma metastatic fig 2 (diagram)

Advanced melanoma (completely removed by surgery)

In a clinical trial of 1019 patients with completely resected melanoma who received Keytruda or placebo:

Keytruda data vs placebo (diagram)

Advanced non-small cell lung cancer (squamous and non-squamous)

Keytruda with chemotherapy

In a clinical trial, 616 patients with metastatic non-squamous non-small cell lung cancer who had not received treatment for metastatic disease were treated with Keytruda plus chemotherapy or placebo plus chemotherapy. At a median follow-up of 11 months:

Clinical trial data for treatment with Keytruda + chemotherapy or placebo + chemotherapy (diagram)

In another clinical trial, 559 patients with metastatic squamous non-small cell lung cancer who had not received treatment for metastatic disease were treated with Keytruda plus chemotherapy or placebo plus chemotherapy. At a median follow-up of 8 months:

Clinical trial data for treatment with Keytruda + chemotherapy or placebo + chemotherapy (diagram)

Keytruda alone as a first treatment

In a clinical trial, 1274 patients with non-small cell lung cancer that tested positive for PD-L1 and that was either stage III and could not be treated with surgery or chemoradiation or was metastatic were treated with Keytruda or chemotherapy. In that trial:

Keytruda vs chemotherapy prognosis (diagram)

In another clinical trial, 305 patients with metastatic non-small cell lung cancer that had high levels of PD-L1 and that was previously untreated were treated with Keytruda or chemotherapy. At a median follow-up of 25 months:

Keytruda vs chemotherapy prognosis (diagram)

Keytruda for previously treated non-small cell lung cancer

In a clinical trial, 1033 patients with metastatic non-small cell lung cancer that tested positive for PD-L1 who had tried chemotherapy containing platinum, and it either did not work or stopped working were treated either with Keytruda or docetaxel (a chemotherapy). At a median follow-up of 43 months:

Data showing results of clinical trials after patients were first treated with chemotherapy and then treated with Keytruda or chemotherapy (diagram)

Advanced small cell lung cancer

In two clinical trials, 83 patients with small cell lung cancer whose cancer had come back or spread after treatment with at least two different types of therapies, including chemotherapy containing platinum, were treated with Keytruda. The following results were observed:

Results after being treated with Keytruda (diagram)

Head and neck squamous cell cancer

Keytruda as a first treatment, either alone or with chemotherapy

In a clinical trial, 882 patients with head and neck squamous cell cancer that had spread who had not previously received treatment for metastatic disease, or whose cancer came back and could not be removed by surgery were treated with either Keytruda alone, Keytruda with chemotherapy, or cetuximab with chemotherapy. At a median follow-up of 13 months:

Results with Keytruda with chemotherapy or with Cetuximab with chemotherapy (diagram)

In patients with tumors that tested positive for PD-L1, at a median follow-up of 12 months:

PD-L1 positive: results with Keytruda with chemotherapy or with Cetuximab with chemotherapy (diagram)

Keytruda for previously treated head and neck squamous cell cancer

In a clinical trial, 174 patients with head and neck squamous cell carcinoma whose cancer had spread or come back after treatment with chemotherapy that contains platinum were treated with Keytruda. At a median follow-up of 9 months:

Results for Keytruda when patients were previously treated with chemotherapy (diagram)

In another clinical trial, 495 patients with head and neck squamous cell carcinoma whose cancer had spread or come back after treatment with chemotherapy that contains platinum were treated with either Keytruda or standard treatment (a choice of methotrexate, docetaxel, or cetuximab). For patients with high PD-L1 expression:

Results after receiving either Keytruda or standard treatment (diagram)

Classical Hodgkin lymphoma

In a clinical trial, 210 patients with classical Hodgkin lymphoma that either had not responded to treatment, or had gotten better, but then came back after treatment were treated with Keytruda. At a median follow-up of 9 months:

Results after being treated and then receiving Keytruda (diagram)

In another clinical trial, 31 patients with classical Hodgkin lymphoma that either had not responded to treatment, or had gotten better, but had then come back after treatment were treated with Keytruda. At a median follow-up of 53 months:

Primary mediastinal B cell lymphoma

In a clinical trial, 53 patients with primary mediastinal B cell lymphoma that either had not responded to treatment, or had gotten better but then came back after treatment were treated with Keytruda. At a median follow-up of 10 months:

Results after being treated and then receiving Keytruda (diagram)

Bladder and urinary tract (urothelial cell) cancer

Keytruda for advanced bladder and urinary tract (urothelial cell) cancer

In a clinical trial, 370 patients with advanced urothelial carcinoma that had grown or spread who could not be treated with a chemotherapy containing cisplatin were treated with Keytruda. At a median follow-up of 8 months:

Patients could not be treated with a chemotherapy containing cisplatin were treated with Keytruda (diagram)

In another clinical trial, 542 patients with advanced urothelial carcinoma that had grown or spread who had been treated with chemotherapy containing platinum, and it did not work or stopped working were treated with Keytruda or chemotherapy. At a median follow-up of 9 months:

Results Keytruda vs chemotherapy (diagram)

Keytruda for high-risk, non-muscle invasive bladder cancer

In a clinical trial, 96 patients with bladder cancer that had not yet spread to nearby tissue, but was at a high risk for spreading (high-risk, non-muscle invasive bladder cancer), who had tried Bacillus Calmette-Guerin treatment, and it either did not work or stopped working, and who either could not or chose not to have their bladder surgically removed, were treated with Keytruda. At a median follow-up of 28 months, 41% of patients had their tumors completely disappear. Of the patients who responded to treatment, 46% continued to respond for 12 months or longer.

Microsatellite instability-high cancer

A total of 149 patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors across five clinical trials were treated with Keytruda. The following results were observed:

Results for 5 clinical trials where patients were treated with Keytruda (diagram)

Advanced stomach cancer

In a clinical trial, 259 patients with gastric or gastroesophageal junction adenocarcinoma that had grown or spread after treatment with at least two types of chemotherapy were treated with Keytruda. Among 143 patients with cancer that tested positive for PD-L1:

Results after receiving Keytruda (diagram)

Advanced esophagus cancer

In a clinical trial, 628 patients with esophageal cancer that had come back or spread who had received at least one treatment, and it either did not work or stopped working were treated with Keytruda or chemotherapy. For the 167 patients whose esophageal squamous cell carcinoma tested positive for PD-L1:

Results Keytruda vs chemotherapy (diagram)

In another clinical trial, 121 patients with esophageal squamous cell carcinoma that had come back or spread who had received at least two treatments, and they either did not work or stopped working were treated with Keytruda. Among the 35 patients with cancers that tested positive for PD-L1:

20% had a response and 71% of responding patients continued to respond for 6 months or longer (diagram)

Advanced cervical cancer

In a clinical trial, 98 patients with cervical cancer that had come back or spread were treated with Keytruda. Among the 77 patients with cancers that tested positive for PD-L1, at a median follow-up time of 12 months:

Results after treatment with Keytruda (diagram)

Advanced liver cancer

In a clinical trial, 104 patients with hepatocellular carcinoma who had been treated with sorafenib (Nexavar), and it either did not work or stopped working, or it was not tolerated, were treated with Keytruda. The following results were observed:

Results after treatment with Keytruda (diagram)

Advanced Merkel cell carcinoma

In a clinical trial, 50 patients with Merkel cell carcinoma that had come back or spread who had not received previous treatment for advanced disease were treated with Keytruda. The following results were observed:

Results after treatment with Keytruda (diagram)

Advanced kidney cancer

In a clinical trial, 861 patients with advanced renal cell carcinoma who had not received previous treatment for advanced disease were treated with Keytruda plus axitinib or with sunitinib. At a median follow-up of 13 months:

Results for treatment with Keytruda plus axitinib or with sunitinib (diagram)

Advanced endometrial carcinoma

In a clinical trial, 108 patients with metastatic endometrial carcinoma who had received treatment, and it did not work or stopped working were treated with Keytruda plus lenvatinib (Lenvima). Among the subgroup of patients whose cancer was not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), at a median follow-up of 19 months:

Results for treatment with Keytruda with lenvatinib (diagram)


What are the side effects?

The most common side effects of Keytruda include fatigue, pain (in the muscles, bones, joints, and stomach area), itching, rash, decreased appetite, diarrhea, constipation, nausea, fever, cough, and shortness of breath.

Keytruda can cause the patient’s T cells to attack healthy cells throughout the body. Because of this, Keytruda can cause side effects that can become serious or life-threatening, and may lead to death. These side effects can happen anytime during treatment or after the treatment has ended. Some of the serious side effects related to Keytruda include inflammation of the lungs, liver, brain, kidneys (which can lead to kidney failure), or colon (which can result in tears or holes in the intestine). Additionally, problems can arise with hormone glands (including thyroid, pituitary, and adrenal glands, as well as the pancreas). Skin rash (which could become severe and life-threatening) and reactions related to the infusion may also occur. Patients should report any symptoms to their healthcare provider who can then initiate actions to limit or reverse the side effects.

Patients may experience other side effects when Keytruda is used in combination with other treatments. For a more complete list of possible side effects, see the full prescribing information.


Additional information

Manufacturer

Merck

Approval

FDA and EMA


Understanding Cancer Immunotherapy Research

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