Les renseignements du Formulaire de médicaments s’adressent aux professionnels de la santé. Il ne s’agit pas d’un avis médical. Certains des renseignements, y compris ceux sur le financement des médicaments anticancéreux, ne s’appliquent pas à tous les patients. Les plans de traitement du cancer sont propres à chaque patient. Si vous êtes un patient, veuillez parler avec votre équipe soignante pour comprendre comment ces renseignements s’appliquent à vous.
PEME+PEMB(MNT)
Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR). Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.
Maintenance treatment for patients who completed first-line pemetrexed and platinum chemotherapy for metastatic non-squamous NSCLC, in adults with no EGFR or ALK genomic tumour aberrations. Treatment should be for patients with good performance status.
pembrolizumab
New Drug Funding Program
(Pembrolizumab - In Combination with Platinum and Pemetrexed for First Line Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC))
After 4 to 6 cycles of CISPPEME+PEMB or CRBPPEME+PEMB - As maintenance treatment:
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pembrolizumab 1 | 2 mg /kg | IV (max 200 mg) | Day 1 |
| pemetrexed | 500 mg /m² | IV | Day 1 |
1Dosing based on NDFP funding criteria. Refer to NDFP form for alternative pembrolizumab dosing schedule.
REPEAT EVERY 21 DAYS
For up to 2 years of pembrolizumab treatment (e.g. 35 cycles given q3 weeks, including the 4-6 cycles combined with chemotherapy*) unless disease progression or unacceptable toxicity occurs**
*CISPPEME+PEMB or CRBPPEME+PEMB
**If chemotherapy is discontinued due to toxicity, pembrolizumab may be continued as single agent: PEMB(MNT).
Refer to NDFP form for details on pembrolizumab retreatment.
Low
- Also refer to CCO Antiemetic Recommendations.
Premedications:
Pemetrexed:
- Starting ≥ 1 week prior to pemetrexed administration, and continued until 3 weeks after last dose:
- Vitamin B12 1000 mcg IM every 9 weeks
- Folic acid 0.4 - 1 mg PO daily
- Dexamethasone 4mg PO BID for 3 days starting day before chemotherapy suggested for rash prophylaxis.
Pembrolizumab (prophylaxis for infusion reactions):
- Routine pre-medication is not recommended.
- May consider antipyretic and H1-receptor antagonist in patients who experienced a grade 1-2 infusion reaction.
Other Supportive Care:
Pemetrexed:
- NSAIDs should be held for 2-5 days prior and 2 days after pemetrexed (refer to pemetrexed drug monograph)
Doses should be modified according to the protocol by which the patient is being treated.
Dosage with toxicity
There are no dose reductions for pembrolizumab. Doses are either delayed or discontinued with toxicity. Dose modifications for pemetrexed are described below.
Pemetrexed:
Hematologic:
| Worst toxicity in previous cycle | Grade | Pemetrexed (% previous dose)* |
| Thrombocytopenic bleeding | 50% | |
| ANC | Grade 4 | 75% |
| Platelets | ≥ Grade 3 | |
| Recurrent myelosuppression after 2 dose reductions | ≥ Grade 3 | Discontinue |
*Start next cycle only when ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L and related organ/non-hematologic toxicity ≤ grade 2 (or recovery to baseline).
Non-hematologic:
| Worst toxicity in previous cycle | Grade | Pemetrexed (% previous dose)* |
| Neurotoxicity | Grade 2 | 100% |
| ≥ Grade 3 | Discontinue | |
| Mucositis | ≥ Grade 3 | 50% |
| Diarrhea | ≥ Grade 3 or requiring hospitalization | 75% |
| Pneumonitis | Any | Hold and investigate; discontinue if confirmed |
| All other related organ / non-hematologic toxicity | Grade 3 | 75% |
| Grade 4 | Discontinue | |
|
Stevens-Johnson syndrome |
Any | |
| Toxic epidermal necrolysis | ||
| Recurrent non-hematologic toxicity after 2 dose reductions | ≥ Grade 3 |
*Start next cycle only when ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L and related organ/non-hematologic toxicity ≤ grade 2 (or recovery to baseline).
Pembrolizumab:
Healthcare professionals should also consult the most recent pembrolizumab product monograph for additional information.
Summary of Principles of Management or immune-related adverse effects (iRAEs)
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Immune-related adverse effects (irAEs) are different in their presentation, onset and duration compared to conventional chemotherapy. Patient and provider education is essential.
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Initial irAE presentation can occur months after completion of treatment and affect multiple organs.
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Dose escalation or reduction is not recommended.
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If no other cause can be identified (such as infection), any new symptom should be considered immune-related and prompt treatment initiated.
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Organ-specific system-based toxicity management is recommended.
Refer to CCO's Immune Checkpoint Inhibitor Toxicity Management Guideline for detailed descriptions of Immune-related toxicities and their management.
Management of Pembrolizumab Infusion-related Reactions:
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
| Grade | Management | Re-challenge |
| 1 or 2 |
Restart:
|
|
| 3 or 4 |
|
|
Hepatic Impairment
No dosage adjustment is recommended for pemetrexed. Pemetrexed is not extensively metabolized in the liver, but has not been studied in hepatic impairment; use with caution. Pembrolizumab recommendations are outlined below.
Refer to CCO's Immune Checkpoint Inhibitor Toxicity Management Guideline for detailed descriptions for immune-related hepatitis management with pembrolizumab.
| Hepatic Impairment | Pembrolizumab Dose |
| Mild (bilirubin 1 - 1.5 x ULN or AST > ULN) | No dose adjustment necessary |
| Moderate (bilirubin >1.5 - 3 x ULN and any AST) | No dose adjustment necessary; limited data |
| Severe (bilirubin > 3 x ULN and any AST) | Caution; no data |
Renal Impairment
Refer to CCO's Immune Checkpoint Inhibitor Toxicity Management Guideline for detailed descriptions for immune-related nephritis management with pembrolizumab.
|
Creatinine clearance (mL/min)
|
Pemetrexed Dose*^
|
Pembrolizumab Dose^ |
| ≥ 45 | No dose adjustment necessary | No dose adjustment necessary |
|
30 to 44
|
Discontinue
|
No dose adjustment necessary |
| < 30 | Discontinue | Caution; no data |
*Exercise caution with co-administration of NSAIDs for patients with CrCl 45-79mL/min.
^Patients were excluded from clinical trials if CrCl was < 50 mL/min. (Gandhi 218, Chu 2023)
Dosage in the Elderly
No dose adjustments are needed for pemetrexed or pembrolizumab, but elderly patients should be monitored closely with pemetrexed as more myelosuppression, renal and severe GI effects were noted.
Refer to pembrolizumab, pemetrexed drug monograph(s) for additional details of adverse effects.
|
Common (25-49%) |
Less common (10-24%) |
Uncommon (< 10%), but may be severe or life-threatening |
|
|
|
Refer to pembrolizumab, pemetrexed drug monograph(s) for additional details.
- Nephrotoxic drugs (e.g. aminoglycosides) may increase the toxicity of pemetrexed and exacerbate nephro- and ototoxicity; caution and monitor closely if used together.
- NSAIDs may increase the toxicity of pemetrexed. Hold NSAIDs with shorter half-lives (e.g. ibuprofen) at least 2 days before to 2 days after pemetrexed. Hold NSAIDs with long half-lives (e.g. piroxicam) 5 days before to 2 days after pemetrexed.
Refer to pembrolizumab, pemetrexed drug monograph(s) for additional details.
Administration
Pembrolizumab:
-
Dilute in 0.9% sodium chloride or D5W to final concentration of 1 to 10 mg/mL; mix by gentle inversion.
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Administer IV over 30 minutes using sterile, non-pyrogenic, low protein-binding 0.2 to 5 micron in-line or add-on filter.
- Administer pembrolizumab before pemetrexed.
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Do not co-administer other drugs through the same infusion line.
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Unopened vials should be stored under refrigeration (2 to 8oC). Protect from light. Do not freeze.
Pemetrexed:
-
Reconstitute as directed with Normal Saline.
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Dilute to a total volume of 100mL (Normal Saline only); infuse IV over 10 minutes.
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Incompatible with calcium-containing solutions.
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Do not co-administer with other drugs and diluents.
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Keep unopened vials at room temperature. Pemetrexed is not light sensitive.
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
Contraindications
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Patients who have a hypersensitivity to these drugs or any of their components.
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Concomitant use of yellow fever vaccine.
Warnings/ Precautions
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Patients with pre-existing cardiovascular risk factors or moderate-severe renal dysfunction.
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Avoid the use of live or live-attenuated vaccines.
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Pembrolizumab may cause serious immune-mediated reactions affecting multiple organ systems, including GI, hepatic, renal, respiratory, endocrine and others. Use with caution and monitor closely in patients with pre-existing conditions such as colitis, hepatic impairment, respiratory or endocrine disorders, such as hypo or hyperthyroidism or diabetes mellitus.
Pregnancy and Lactation:
- This regimen is not recommended for use in pregnancy. Adequate contraception should be used by patients and their partners while on treatment and after the last treatment dose. Recommended methods and duration of contraception may differ depending on the treatment. Refer to the drug monograph(s) for more information.
- Breastfeeding is not recommended during this treatment and after the last treatment dose. Refer to the drug monograph(s) for recommendations after the last treatment dose (if available).
- Fertility effects:
- Pemetrexed: Yes (may be irreversible; Sperm preservation should be considered prior to starting treatment)
- Pembrolizumab: Unknown
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Recommended Clinical Monitoring
- CBC; Baseline and before each cycle
- Liver function tests; Baseline and before each cycle
- Renal function tests, including serum creatinine and urine protein; Baseline and before each cycle
- Electrolytes; Baseline and as clinically indicated
- Blood glucose; Baseline and as clinically indicated
- Thyroid function tests; Baseline and as clinically indicated
- Clinical toxicity assessment for fatigue, infusion-related and immune-mediated reactions, thromboembolism, infection, bleeding, ocular, endocrine, skin, GI, neurologic, musculoskeletal, cardiac and respiratory effects ; At each visit
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Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
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Pembrolizumab drug monograph. Ontario Health (Cancer Care Ontario).
Pemetrexed drug monograph. Ontario Health (Cancer Care Ontario).
Gandhi et al. Pembrolizumab plus chemotherapy in metastatic non-small cell lung cancer. N Engl J Med;378(22):2078-92.
February 2026 Expanded to full regimen monograph
Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph. Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.