Pembrolizumab (Keytruda)

Pembrolizumab: pem-broh-LIH-zoo-mab

Keytruda: kee-TROO-duh

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
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
Tumor mutational burden-high cancer
Cutaneous squamous cell carcinoma
Breast cancer

Advanced melanoma

Keytruda is approved for:

• Adult 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.
• Adult and pediatric patients (12 years and older) with stage IIB, IIC, or III melanoma that 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.
• Patients with stage IB, II, or IIIA non-small cell lung cancer. Keytruda is used by itself after surgical removal of all known disease and platinum-based chemotherapy.

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 cancer 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 patients with classical Hodgkin lymphoma that either has not responded to treatment, or got better, but then came back.
• Pediatric patients with classical Hodgkin lymphoma that either has not responded to treatment, or got better, but then came back after two 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
  • who cannot be treated with any chemotherapy containing platinum.
• Patients with advanced urothelial carcinoma (the most common type of bladder and urinary tract cancer) that has grown or spread, and who cannot be treated with cisplatin-containing chemotherapy. In such cases, Keytruda is used in combination with enfortumab vedotin (Padcev).

• 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 (MSI-H) or mismatch repair-deficient (dMMR) cancer, including colorectal cancer and endometrial cancer

Keytruda is approved for:

• Adult and pediatric patients with previously treated microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors (including colorectal, endometrial, biliary, gastric or gastroesophageal junction, pancreatic, small intestinal, prostate, breast, bladder, renal cell, small cell lung, sarcoma, mesothelioma, thyroid, brain, ovarian, cervical, neuroendocrine, and other cancers), whose cancer has spread or cannot be removed by surgery and who have no other satisfactory treatment options available.
• Patients with previously untreated microsatellite instability-high (MSI-H) or mismatch repair- deficient (dMMR) colon or rectal cancer that cannot be removed by surgery or has spread to other parts of the body. In such cases, Keytruda may be used as a first treatment.
• Patients with previously treated, advanced, microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) endometrial cancer that cannot be removed by surgery or treated with radiation. In such cases, Keytruda may be used by itself.

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 cannot be removed by surgery, and that tests positive for the HER2 molecule. In such cases, Keytruda is used in combination with trastuzumab (e.g., Herceptin) and chemotherapy containing platinum and fluoropyrimidine.

Advanced esophagus cancer

Keytruda is approved for:

• Patients with esophageal cancer that has spread to nearby lymph nodes or other parts of the body, cannot be removed by surgery or treated with concurrent chemotherapy and radiation, and tests positive for the PD-L1 molecule, and who have received at least one treatment that either did not work or stopped working. In such cases, Keytruda is used on its own.
• Patients with esophageal cancer that has spread to nearby lymph nodes or other parts of the body and cannot be removed by surgery or treated with concurrent chemotherapy and radiation. In such cases, Keytruda may be used in combination with chemotherapy containing platinum and fluoropyrimidine.

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.
• Patients with cervical cancer that has come back or spread to other parts of the body and tests positive for the PD-L1 molecule. In such cases, Keytruda is used in combination with chemotherapy and, in some cases, bevacizumab (Avastin, Mvasi, Zirabev).

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 axitinib (Inlynta) as a first treatment.
• Patients with renal cell carcinoma (kidney cancer) whose cancer-affected kidney and other tissue the cancer had spread to (metastases) had been partially or completely removed by surgery, and who are at intermediate or high risk for the cancer to come back. In such cases, patients may be treated with Keytruda following surgery.

Advanced endometrial carcinoma

Keytruda is approved for:

• Patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR), and who have received prior treatment that did not work or stopped working, and who cannot receive surgery or radiation. In such cases, Keytruda may be used in combination with lenvatinib (Lenvima).
• Patients with previously treated advanced endometrial cancer that is microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR), and whose cancer cannot be removed by surgery or treated with radiation. In such cases, Keytruda may be used by itself.

Tumor mutational burden-high cancer

Keytruda is approved for:

• Adult and pediatric patients with solid tumors whose cancer:

  • cannot be removed by surgery or has spread to other parts of the body, AND
  • has a high number of genetic mutations (changes) in the cancer cells, AND
  • who have received prior treatment, but it did not work or stopped working, and no other satisfactory treatment options are available.

Cutaneous squamous cell carcinoma

Keytruda is approved for:

• Patients with cutaneous squamous cell carcinoma (a type of skin cancer) that has spread or come back, and could not be removed by surgery or be cured by radiation.

Triple-negative breast cancer

Keytruda is approved for:

• Patients with triple-negative breast cancer (cancer that tests negative for estrogen hormone receptor, progesterone hormone receptor, and human epidermal growth factor receptor 2 [HER2]) that has come back and grown at the original tumor site or spread to other parts of the body, cannot be removed by surgery, and tests positive for the PD-L1 molecule. In such cases, Keytruda is used in combination with chemotherapy.
• Patients with early-stage triple-negative breast cancer who are at a high risk for the cancer to become worse. In such cases, Keytruda is used in combination with chemotherapy before surgical removal of all known disease and by itself after surgery. 

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, Merkel cell carcinoma, microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) cancers, and tumor mutational burden high (TMB-H) cancers. The safety and efficacy of Keytruda in pediatric patients with MSI-H and TMB-H central nervous system cancers have not been established. The safety and efficacy of Keytruda in pediatric patients with any other cancer type 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.
Complications of stem cell transplant: Serious and life-threatening complications, which can lead to death, can occur in patients who have received a stem cell transplant from a stem cell donor before or after being treated with Keytruda.
Solid organ transplant rejection: Treatment with Keytruda can increase the risk of rejection in patients who have received a solid organ transplant.

Checkpoint Blockade

• PD-1 blockade

• 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.

Keytruda is administered via a tube into a vein (intravenous infusion, or I.V.) over 30 minutes every three weeks or every six weeks, depending on the cancer type, treatment combination, dose, and the age of the patient (adult or pediatric).

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)
Head and neck squamous cell cancer
Classical Hodgkin lymphoma
Primary mediastinal B cell lymphoma
Bladder and urinary tract (urothelial cell) cancer
Microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) cancer, including colorectal cancer
Advanced stomach cancer
Advanced esophagus cancer
Advanced cervical cancer
Advanced liver cancer
Advanced Merkel cell carcinoma
Advanced kidney cancer
Advanced endometrial carcinoma
Tumor mutational burden-high (TMB-H) cancer
Cutaneous squamous cell carcinoma
Triple-negative breast cancer

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 melanoma that could not be removed by surgery or had spread to other parts of the body, and who had no prior treatment with Yervoy (ipilimumab) – another form of immunotherapy) received either Keytruda or Yervoy. At a median follow-up of 23 months:

In another clinical trial, 540 patients with melanoma that could not be removed by surgery or had spread to other parts of the body, and did not respond to or progressed on Yervoy (ipilimumab) received either Keytruda or chemotherapy. At a median follow-up of 18 months:

Advanced melanoma (completely removed by surgery)

In a clinical trial, 976 adult and pediatric patients (12 years and older) with previously untreated stage IIB or IIC melanoma (deep or ulcerated tumors at original site) that was completely removed by surgery, were treated with or placebo for up to one year. At a median follow-up of 14 months:

In another clinical trial, 1019 patients with stage III melanoma that was, together with the lymph nodes that contained cancer, completely removed by surgery, were treated with Keytruda or placebo. At a median follow-up of 15 months:

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 (pemetrexed and cisplatin or carboplatin), OR
• placebo plus chemotherapy.

At a median follow-up of 11 months:

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 (carboplatin and paclitaxel or paclitaxel protein-bound), OR
• placebo plus chemotherapy.  At a median follow-up of 8 months:

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 (pemetrexed and carboplatin followed by optional pemetrexed OR paclitaxel and carboplatin followed by optional pemetrexed). In that trial:

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 a platinum-based chemotherapy. At a median follow-up of 25 months:

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:

Keytruda for non-small cell lung cancer after surgical removal

In a clinical trial, 1010 patients with stage IB, II, or IIIA non-small cell lung cancer whose cancer was removed by surgery and who were treated with a short course of platinum-based chemotherapy following surgery, were treated with either Keytruda or placebo for up to one year.

(For the definition of “median”, click HERE.)

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 (carboplatin or cisplatin and fluorouracil), or cetuximab (Erbitux) with chemotherapy. At a median follow-up of 13 months:

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:

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:

In another clinical trial, 304 adult patients with patients with classical Hodgkin lymphoma that either has not responded to treatment, or got better, but then came back after at least one combination treatment were treated with either Keytruda or brentuximab vedotin. At a median follow-up of 25 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:

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 platinum-based chemotherapy were treated with Keytruda. At a median follow-up of 11 months:

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 (investigator's choice of paclitaxel, docetaxel, or vinflunine). At a median follow-up of 9 months:

Keytruda for advanced bladder and urinary tract (urothelial cell) cancer not suited for cisplatin-containing chemotherapy

In a clinical trial, 121 patients with bladder and urinary tract cancer (urothelial cancer) that had grown or spread to other parts of the body, who had not received treatment for their advanced disease and were not suited to receive cisplatin-containing chemotherapy, were treated with Keytruda and enfortumab vedotin (Padcev).

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 (MSI-H) or mismatch repair-deficient (dMMR) cancer

Keytruda for previously treated MSI-H or dMMR cancers, including colorectal cancer

A total of 504 patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors across three clinical trials were treated with Keytruda. At a median follow-up of 20 months, the following results were observed:

Keytruda for previously untreated MSI-H or dMMR colorectal cancer

In a clinical trial, 307 patients with previously untreated microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colon or rectal cancer that could not be removed by surgery or had spread to other parts of the body received either Keytruda or the investigator’s choice of the following chemotherapies:

• mFOLFOX6 (oxaliplatin, leucovorin, and fluorouracil)
• mFOLFOX6 (oxaliplatin, leucovorin, and fluorouracil) in combination with either bevacizumab (Avastin, Mvasi, Zirabev) or cetuximab (Erbitux)
• FOLFIRI (irinotecan, leucovorin, and fluorouracil)
• FOLFIRI (irinotecan, leucovorin, and fluorouracil) in combination with either bevacizumab (Avastin, Mvasi, Zirabev) or cetuximab (Erbitux)

At a median follow-up of 38 months:

Advanced stomach cancer

In a clinical trial, 264 patients with a gastric or gastroesophageal junction adenocarcinoma that had spread to nearby lymph nodes or other parts of the body, could not be removed by surgery  and tested positive for the HER2 molecule were treated with Keytruda plus trastuzumab (e.g., Herceptin) and chemotherapy (cisplatin and fluorouracil or oxaliplatin and capecitabine), or trastuzumab and chemotherapy alone.

(For the definition of "median" click HERE.)

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 (paclitaxel, docetaxel, or irinotecan). For the 167 patients whose esophageal squamous cell carcinoma tested positive for high levels of PD-L1:

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:

In another clinical trial, 749 patients with esophageal cancer that had spread to nearby lymph nodes or other parts of the body and could not be removed by surgery or treated with concurrent chemotherapy and radiation, were treated with Keytruda plus cisplatin and fluoropyrimidine chemotherapy, or with placebo plus chemotherapy.

(For the definition of “median”, click HERE.)

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:

In another clinical trial, 617 patients with cervical cancer that had come back or spread to other parts of the body (metastatic) and who had not yet been treated with chemotherapy (except radiochemotherapy) for their metastatic disease, were treated with either

• Keytruda plus chemotherapy (paclitaxel and cisplatin or carboplatin) with or without bevacizumab (Avastin, Mvasi, Zirabev), OR
• Placebo plus chemotherapy with or without bevacizumab

Among 548 patients whose tumor tested positive for the PD-L1 molecule, 63% of patients received bevacizumab as part of the treatment.

(For the definition of “median”, click HERE.)

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:

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:

Advanced kidney cancer

First treatment for 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:

In another clinical trial, 1069 patients with advanced renal cell carcinoma (kidney cancer) were treated with either: 

• Keytruda in combination with lenvatinib, OR
• lenvatinib in combination with everolimus, OR
• sunitinib as a first treatment.  

At a median follow-up o f 27 months:

Treatment following surgery for advanced kidney cancer

In a clinical trial, 994 patients with renal cell carcinoma (kidney cancer) whose cancer-affected kidney and other tissue the cancer had spread to (metastases) had been partially or completely removed by surgery, and who were at intermediate or high risk for the cancer to come back, were treated with Keytruda or placebo following surgery. After 2 years:

Advanced endometrial carcinoma

Endometrial cancer that is not MSI-H or dMMR

In a clinical trial, 697 patients with metastatic endometrial carcinoma whose cancer was not microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) who had received treatment (including platinum-based chemotherapy), and it did not work or stopped working, were treated with Keytruda plus lenvatinib (Lenvima) or chemotherapy (doxorubicin or paclitaxel) alone. At a median follow-up of 11 months:

Endometrial cancer that is not MSI-H or dMMR

In a clinical trial, 90 patients with previously treated advanced endometrial cancer that was microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR), and whose cancer could not be removed by surgery or treated with radiation, were treated with Keytruda. At a median follow-up of 16 months:

Tumor mutational burden-high (TMB-H) cancer

In a clinical trial, 102 patients with previously treated solid tumors (including small cell lung, cervical, endometrial, anal, vulvar, neuroendocrine, salivary, thyroid, and mesothelioma cancer) whose cancer could not be removed by surgery or had spread, and whose cancer had a high tumor mutational burden, were treated with Keytruda. At a median follow-up of 11 months:

Cutaneous squamous cell carcinoma

In a clinical trial, 105 patients with cutaneous squamous cell carcinoma (a type of skin cancer) that had spread to other parts of the body or had come back (metastatic or recurrent) and 54 patients with cutaneous squamous cell carcinoma that at grown (locally advanced), were treated with Keytruda. At a median follow-up of 24 months for patients with metastatic or recurrent disease and 13 months for patients with locally advanced disease:

Triple-negative breast cancer

In a clinical trial, 847 patients with triple-negative breast cancer that had come back and grown at the original tumor site or had spread to other parts of the body, could not be removed by surgery, and who had not been previously treated with chemotherapy for their advanced disease, were either treated with Keytruda or placebo in combination with chemotherapy (paclitaxel, OR paclitaxel protein-bound, OR gemcitabine and carboplatin). In 323 patients whose tumors were found to produce high levels of PD-L1, the following results were observed:

In another clinical trial, 1174 patients with newly diagnosed, previously untreated, early-stage triple-negative breast cancer who were at a high risk for the cancer to become worse, were treated with:

• Keytruda in combination with chemotherapy before surgical removal of all known disease and Keytruda alone after surgery, OR
• placebo in combination with chemotherapy before surgical removal of all known disease and placebo alone after surgery.

At a median follow-up of 39 months:

The most common side effects of Keytruda include fatigue, pain (in the muscles, bones, joints, and stomach area), headache, 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.

In patients who are treated with Keytruda before or after stem cell transplant, serious and life-threatening transplant-related complications can occur. These complications may arise even if patients have been treated with other types of therapy in between administration of Keytruda and stem cell transplant.

For a more complete list of possible side effects, see the full prescribing information.

Manufacturer

Merck

Approval

FDA and EMA

Links to drug websites

• US: https://www.keytruda.com/
• Europe: https://www.ema.europa.eu/en/medicines/human/EPAR/keytruda

Other references

• https://www.ashclinicalnews.org/on-location/other-meetings/keynote-204-pembrolizumab-superior-brentuximab-relapsed-refractory-classic-hodgkin-lymphoma/
• https://ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.1000
• Phase 3 KEYNOTE-775 Trial in Advanced Endometrial Cancer. Westin SN, et al. OncLive (2021)
• Event-Free Survival Improvement Noted in KEYNOTE-522 Study for Patients with Triple-Negative Breast Cancer. Cancer Network (2021)
• https://www.esmo.org/newsroom/press-office/adjuvant-immunotherapy-prolongs-recurrence-free-survival-in-resected-stage-ii-b-c-melanoma
• Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma. Eggermont AMM, et al. The New England Journal of Medicine (2018)
  
  Last updated: April 27, 2023.

Pembrolizumab: pem-broh-LIH-zoo-mab

Keytruda: kee-TROO-duh

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
Head and neck squamous cell cancer
Classical Hodgkin lymphoma
Bladder and urinary tract (urothelial cell) cancer
Kidney cancer
Microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) cancer, including colorectal, endometrial, gastric, small intestine, and biliary cancer
Esophagus cancer
Breast cancer
Endometrial cancer
Cervical cancer

Advanced melanoma

Keytruda is approved for:

• Adult and pediatric patients (12 years and older) 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.
• Adult and pediatric patients (12 years and older) with stage IIB, IIC, or III 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
  • has spread

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 grown or 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.

Head and neck squamous cell cancer

Keytruda is approved for:

• Patients with head and neck squamous cell cancer that has spread or come back after treatment with chemotherapy that contains platinum and tests positive for high amounts of the PD-L1 molecule.
• Patients with head and neck squamous cell cancer that has spread or come back after previous treatment and tests positive for high amounts of the PD-L1 molecule, and who have been treated for their advanced disease. In such cases, Keytruda is used on its own or in combination with chemotherapy containing platinum and 5-fluorouracil. 

Classical Hodgkin lymphoma

Keytruda is approved for:

• Adult and pediatric patients (3 years and older) with classical Hodgkin lymphoma who have been previously treated with autologous stem cell transplant and it did not work or stopped working, or who were not eligible to receive the transplant and have received at least two prior therapies.

Advanced 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:

  • 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.

Advanced kidney cancer

Keytruda is approved for:

• Patients with renal cell carcinoma (kidney cancer) that has grown or spread. In such cases, Keytruda may be used in combination with axitinib (Inlyta) OR lenvatinib (Lenvima) as a first treatment.
• Patients with renal cell carcinoma (kidney cancer) whose cancer-affected kidney and other tissue the cancer had spread to (metastases) has been partially or completely removed by surgery and who are at increased risk for the cancer to come back. In such cases, patients may be treated with Keytruda following surgery.

Microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) cancer, including colorectal , endometrial, gastric, small intestine, and biliary cancer

Keytruda is approved for: 

• Patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer that has spread to other parts of the body . In such cases, Keytruda may be used on its own as a first treatment.
• Patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer that cannot be removed by surgery or has spread to other parts of the body and has previously been treated with fluoropyrimidine-based chemotherapy. In such cases, Keytruda may be used by itself.
• Patients with advanced, microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) uterus (endometrial) cancer that has been previously treated with platinum-based chemotherapy and cannot be removed by surgery or treated with radiation. In such cases, Keytruda may be used by itself.
• Patients with previously treated microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) stomach (gastric), small bowel (small intestine), or bile duct or gallbladder (biliary) cancer, whose cancer has spread or cannot be removed by surgery.

Esophagus cancer

Keytruda is approved for:

• Patients with previously untreated esophageal cancer that has spread to nearby lymph nodes or other parts of the body, cannot be removed by surgery, and tests positive for the PD-L1 molecule. In such cases, Keytruda is used as a first treatment in combination with chemotherapy containing platinum and fluoropyrimidine. 
• Patients with previously untreated gastroesophageal junction adenocarcinoma that has spread to nearby lymph nodes or other parts of the body, cannot be removed by surgery, and tests positive for the PD-L1 molecule and negative for the HER-2 molecule. In such cases, Keytruda is used as a first treatment in combination with chemotherapy containing platinum and fluoropyrimidine. 

Triple-negative breast cancer

Keytruda is approved for:

• Patients with triple-negative breast cancer (cancer that tests negative for estrogen hormone receptor, progesterone hormone receptor, and human epidermal growth factor receptor 2 [HER2]) that

  • has come back and grown at the original tumor site or has spread to other parts of the body, cannot be removed by surgery,
  • tests positive for the PD-L1 molecule, and
  • who have not been treated with chemotherapy for their advanced disease.

In such cases, Keytruda is used in combination with chemotherapy.

• Patients with early-stage triple-negative breast cancer who are at a high risk for the cancer to become worse. In such cases, Keytruda is used in combination with chemotherapy before surgical removal of all known disease, and by itself after surgery.

Advanced endometrial carcinoma

Keytruda is approved for:

• Patients with endometrial carcinoma that has grown at the original tumor site or come back, and who have received prior treatment with platinum-containing chemotherapy that did not work or stopped working, and who cannot receive surgery or radiation. In such cases, Keytruda may be used in combination with lenvatinib (Lenvima).

Advanced cervical cancer

Keytruda is approved for:

• Patients with advanced cervical cancer that has come back or spread to other parts of the body and tests positive for the PD-L1 molecule. In such cases, Keytruda is used in combination with chemotherapy and, in some cases, bevacizumab (Avastin, Mvasi, Zirabev).

Limitations of use

Age: The safety and efficacy of Keytruda has been established in pediatric patients (12 years and older) with melanoma and pediatric patients (3 years and older) with classical Hodgkin lymphoma. The safety and efficacy of Keytruda in pediatric patients (under 12 years of age) with melanoma, pediatric patients (under 3 years of age) with classical Hodgkin lymphoma, and pediatric patients (under 18 years of age) with any other cancer type 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.
Complications of stem cell transplant: Serious and life-threatening complications, which can lead to death, can occur in patients who have received a stem cell transplant from a stem cell donor before or after being treated with Keytruda.
Solid organ transplant rejection: Treatment with Keytruda can increase the risk of rejection in patients who have received a solid organ transplant.

Checkpoint Blockade

• PD-1 blockade

• 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.

Keytruda is administered via a tube into a vein (intravenous infusion, or i.v.) over 30 minutes either every three weeks or every six weeks, depending on the cancer type, treatment combination, and dose.

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)
Head and neck squamous cell cancer
Classical Hodgkin lymphoma
Advanced bladder and urinary tract (urothelial cell) cancer
Advanced kidney cancer
Microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer
Microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) endometrial, gastric, small intestine, or biliary cancer
Esophagus cancer
Triple-negative breast cancer
Advanced endometrial cancer
Advanced cervical cancer

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 melanoma that could not be removed by surgery and had spread to other parts of the body, and who had no prior treatment with ipilimumab (Yervoy - another form of immunotherapy) received either Keytruda or Yervoy. At a median follow-up of 23 months:

In another clinical trial, 540 patients with melanoma that could not be removed by surgery, had spread to other parts of the body, and did not respond to or progressed on Yervoy (ipilimumab) received either Keytruda or chemotherapy. At a median follow-up of 18 months:

In another clinical trial, 276 patients with advanced melanoma who had been previously treated with ipilimumab (Yervoy) or who had not been treated with ipilimumab before, were treated with Keytruda. At a minimum follow-up of 30 months:

Advanced melanoma (completely removed by surgery)

In a clinical trial, 1019 adult patients with stage III melanoma that, together with the lymph nodes that contain cancer, was completely removed by surgery, were treated with either Keytruda or placebo:

At a median follow-up of 46 months:

In another clinical trial, 976 adults and pediatric patients (12 years and older) with stage IIB or IIC melanoma that, together with the lymph nodes that contain cancer, was completely removed by surgery, were treated with either Keytruda or placebo. At a median follow-up of 27 months:

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 19 months:

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 14 months:

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 had spread to other parts of the body, were treated with Keytruda or chemotherapy. Among 599 patients with high levels of PD-L1, at a median follow-up of 15 months:

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 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:

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, and 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:

At a median follow-up of 12 months:

Keytruda for previously treated head and neck squamous cell cancer

In a 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 129 patients with high PD-1 expression:

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 63 months:

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:

In another clinical trial, 304 adult patients with patients with classical Hodgkin lymphoma that either has not responded to treatment, or got better, but then came back after at least one combination treatment were treated with either Keytruda or brentuximab vedotin (Adcetris). Among the first 149 patients, at a median follow-up of 25 months:

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 11 months:

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:

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 38 months:

In another clinical trial, 1069 patients with advanced renal cell carcinoma were treated with either:

• Keytruda in combination with lenvatinib OR
• lenvatinib in combination with everolimus OR
• sunitinib as a first treatment.

At a median follow-up of 27 months:

Treatment following surgery for advanced kidney cancer

In a clinical trial, 994 patients with renal cell carcinoma (kidney cancer) whose cancer-affected kidney and other tissue the cancer had spread to (metastases) had been partially or completely removed by surgery, and who were at intermediate or high risk for the cancer to come back, were treated with Keytruda or placebo following surgery. At a median follow-up of 30 months:

Microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer

In a clinical trial, 124 patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer that could not be removed by surgery or had spread to other parts of the body and had previously been treated with fluoropyrimidine-based chemotherapy, were treated with Keytruda. At a median follow-up of 37 months:

Microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) endometrial, gastric, small intestine, or biliary cancer

In another clinical trial, 355 patients with previously treated microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid cancer, including patients with endometrial, gastric, small intestine, or biliary cancer, whose cancer has spread or cannot be removed by surgery, were treated with Keytruda.

For 83 patients with endometrial cancer at a median follow-up of 22 months:

For 51 patients with gastric cancer at a median follow-up of 14 months:

For 27 patients with small intestine cancer at a median follow-up of 29 months:

For 22 patients with biliary cancer at a median follow-up of 19 months:

In a clinical trial, 307 patients with previously untreated microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer that had spread to other parts of the body were treated with Keytruda or the investigator’s choice of the following chemotherapies:

• mFOLFOX6 (oxaliplatin, leucovorin, and fluorouracil)
• mFOLFOX6 (oxaliplatin, leucovorin, and fluorouracil) in combination with either bevacizumab (Avastin, Mvasi, Zirabev) or cetuximab (Erbitux)
• FOLFIRI (irinotecan, leucovorin, and fluorouracil)
• FOLFIRI (irinotecan, leucovorin, and fluorouracil) in combination with either bevacizumab (Avastin, Mvasi, Zirabev) or cetuximab (Erbitux)

At a median follow-up of 38 months: 

Esophagus cancer

In a clinical trial, 383 previously untreated patients with esophageal cancer or gastroesophageal junction adenocarcinoma that tested positive for the PD-L1 molecule and negative for the HER-2 molecule, were treated with either Keytruda and chemotherapy (cisplatin and fluorouracil (5-FU)) or placebo and chemotherapy. 

At a median follow-up of 14 months: 

Triple-negative breast cancer

In a clinical trial, 847 patients with triple-negative breast cancer that had come back and grown at the original tumor site or had spread to other parts of the body, could not be removed by surgery, and who had not been previously treated with chemotherapy for their advanced disease, were either treated with Keytruda or placebo in combination with chemotherapy (paclitaxel, OR paclitaxel protein-bound, OR gemcitabine and carboplatin). In 323 patients whose tumors were found to produce high levels of PD-L1, the following results were observed at a median follow-up of 20 months:

In another clinical trial, 1174 patients with newly diagnosed, previously untreated, early-stage triple-negative breast cancer who were at a high risk for the cancer to become worse, were treated with:

• Keytruda in combination with chemotherapy before surgical removal of all known disease and Keytruda alone after surgery, OR
• placebo in combination with chemotherapy before surgical removal of all known disease and placebo alone after surgery.

At a median follow-up of 38 months:

Advanced endometrial carcinoma

In a clinical trial, 827 patients with metastatic endometrial carcinoma who had received treatment (including platinum-based chemotherapy), and it did not work or stopped working, were treated with Keytruda plus lenvatinib (Lenvima) or chemotherapy (doxorubicin or paclitaxel) alone.
At a median follow-up of 11 months:

Advanced cervical cancer

In a clinical trial, 617 patients with cervical cancer that had come back or spread to other parts of the body (metastatic) and who had not yet been treated with chemotherapy (except radiochemotherapy) for their metastatic disease, were treated with either

• Keytruda plus chemotherapy (paclitaxel and cisplatin or carboplatin) with or without bevacizumab (Avastin, Mvasi, Zirabev), OR
• Placebo plus chemotherapy with or without bevacizumab

Among 548 patients whose tumor tested positive for the PD-L1 molecule, 63% of patients received bevacizumab as part of the treatment. At a median follow-up of 17 months:

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.

Manufacturer

Merck

Approval

FDA and EMA

Links to drug websites

• US: https://www.keytruda.com/
• Europe: https://www.ema.europa.eu/en/medicines/human/EPAR/keytruda

Last updated on January 30, 2023