Keytruda vs. OPDIVO: Head-to-Head Comparison of Leading PD-1 Inhibitors

Keytruda (pembrolizumab) and OPDIVO (nivolumab) are the two most widely used PD-1 checkpoint inhibitors, with similar mechanisms but important differences in approvals, dosing, and clinical data.

**Mechanism of Action - Nearly Identical**

Both Are PD-1 Inhibitors:
- Block PD-1 receptor on T-cells
- Prevent cancer cells from evading immune system
- Enable immune destruction of tumors
- Humanized monoclonal antibodies

Chemical Differences:
- Keytruda: Humanized IgG4-kappa antibody
- OPDIVO: Fully human IgG4 antibody
- Clinical significance minimal

**FDA-Approved Cancers**

Keytruda Approvals (20+ cancer types):
- Melanoma, NSCLC, Head & neck, Hodgkin lymphoma
- Urothelial carcinoma, MSI-H/dMMR solid tumors
- Gastric/GEJ cancer, Cervical cancer
- Hepatocellular carcinoma, Merkel cell carcinoma
- Renal cell carcinoma, Endometrial carcinoma
- Cutaneous squamous cell carcinoma
- Triple-negative breast cancer
- Tumor Mutational Burden-High (TMB-H) cancers

OPDIVO Approvals (15+ cancer types):
- Melanoma, NSCLC, Renal cell carcinoma
- Hodgkin lymphoma, Head & neck cancer
- Urothelial carcinoma, MSI-H/dMMR colorectal
- Hepatocellular carcinoma, Esophageal cancer
- Gastric/GEJ cancer, Mesothelioma

Unique to Keytruda:
- TMB-H solid tumors (tissue-agnostic)
- Triple-negative breast cancer
- Cervical cancer
- Several others

Unique to OPDIVO:
- Mesothelioma
- Approved for OPDIVO + Yervoy combinations in more settings

Winner: Keytruda (more FDA approvals overall)

**Efficacy Comparison by Cancer Type**

Melanoma:

Keytruda:
- 5-year survival: 43% (monotherapy)
- Approved first-line and adjuvant

OPDIVO:
- 5-year survival: 44% (monotherapy)
- 5-year survival: 52% (+ Yervoy combination)
- OPDIVO + Yervoy most effective melanoma immunotherapy

Winner: OPDIVO + Yervoy combination superior; monotherapy comparable

NSCLC:

Keytruda:
- First approved for PD-L1 ≥50%
- Median OS: 30 months (PD-L1 high)
- Approved with chemotherapy all PD-L1 levels

OPDIVO:
- Initially second-line only
- Now approved first-line with chemo/Yervoy
- Similar efficacy to Keytruda combinations

Winner: Keytruda (more established first-line)

Renal Cell Carcinoma:

Keytruda:
- Keytruda + axitinib combination approved
- Effective first-line option

OPDIVO:
- OPDIVO + Yervoy most effective immunotherapy combination
- OPDIVO + cabozantinib also very effective
- More extensive RCC data

Winner: OPDIVO (more combination data)

Head & Neck Cancer:

Keytruda:
- Approved first-line monotherapy (PD-L1 ≥1)
- Approved with chemotherapy
- Improved survival vs. chemotherapy alone

OPDIVO:
- Second-line after platinum failure
- Approved first-line in some settings

Winner: Keytruda (broader first-line use)

**Dosing and Administration**

Keytruda:
- 200 mg IV every 3 weeks, OR
- 400 mg IV every 6 weeks
- Flat dosing (not weight-based)
- 30-minute infusion

OPDIVO:
- 240 mg IV every 2 weeks, OR
- 480 mg IV every 4 weeks
- Flat dosing
- 30-60 minute infusion

Convenience:
- Keytruda every 6 weeks: Most convenient
- OPDIVO every 4 weeks: Second best
- Keytruda every 3 weeks / OPDIVO every 2 weeks: Similar

Winner: Keytruda (option for every 6 weeks)

**Side Effect Profile**

Overall Toxicity - Very Similar:

Immune-Related Adverse Events:
- Keytruda: 27-37% any grade, 9-17% Grade 3-4
- OPDIVO: 25-35% any grade, 7-15% Grade 3-4
- Practically equivalent

Common Side Effects Both Drugs:
- Fatigue (25-30%)
- Rash/pruritus (15-25%)
- Diarrhea (12-20%)
- Nausea (10-15%)
- Decreased appetite (10-15%)

Specific Toxicity Rates:

Pneumonitis:
- Keytruda: 3-5%
- OPDIVO: 3-4%
- Similar rates

Colitis:
- Keytruda: 2-3%
- OPDIVO: 2-3%
- Similar rates

Hepatitis:
- Keytruda: 1-2%
- OPDIVO: 2-3%
- OPDIVO slightly higher

Thyroid Dysfunction:
- Keytruda: 8-10%
- OPDIVO: 7-9%
- Similar rates

Winner: Tie (virtually identical safety profiles)

**Treatment Duration**

Keytruda:
- FDA label: up to 24 months (2 years)
- Can stop at 2 years if responding
- Durable responses off-treatment common
- Some continue beyond 2 years off-label

OPDIVO:
- No specific duration limit in label
- Continue until progression or toxicity
- Practice varies by oncologist
- Some treat for 2 years similar to Keytruda

Winner: Keytruda (clearer endpoint)

**Cost Comparison**

Both Extremely Expensive:
- Keytruda: ~$12,000-14,000 per dose
- OPDIVO: ~$11,000-13,000 per dose

Annual Cost:
- Keytruda every 3 weeks: ~$190,000-220,000/year
- Keytruda every 6 weeks: ~$95,000-110,000/year
- OPDIVO every 2 weeks: ~$260,000-300,000/year
- OPDIVO every 4 weeks: ~$130,000-150,000/year

Winner: Keytruda every 6 weeks (lowest annual cost)

Note: Insurance coverage and patient assistance programs make actual patient cost variable.

**Clinical Trial Data - Quality and Quantity**

Keytruda:
- Earlier market entry for some indications
- Larger trials in some cancers (KEYNOTE series)
- More aggressive clinical development

OPDIVO:
- Extensive clinical trial program (CheckMate series)
- More combination studies with Yervoy
- Strong data in melanoma and RCC

Winner: Tie (both have robust clinical data)

**Combination Potential**

Keytruda Combinations:
- + Chemotherapy (multiple cancers)
- + Targeted therapies (lenvatinib, axitinib)
- + Other immunotherapies (investigational)

OPDIVO Combinations:
- + Yervoy (CTLA-4 inhibitor) - multiple approvals
- + Chemotherapy
- + Targeted therapies (cabozantinib, etc.)
- More dual checkpoint blockade approvals

Winner: OPDIVO (established dual checkpoint combinations)

**Which One Should You Choose?**

Factors Favoring Keytruda:
- Your cancer type has Keytruda approval but not OPDIVO
- Prefer every 6-week dosing schedule
- TMB-H or MSI-H tumor (Keytruda approved)
- NSCLC with high PD-L1 (strong first-line data)

Factors Favoring OPDIVO:
- Melanoma or RCC needing aggressive dual therapy (+ Yervoy)
- Your cancer type approved for OPDIVO but not Keytruda
- Mesothelioma
- Your oncologist more experienced with OPDIVO

Factors That Don't Matter (Same for Both):
- Side effect profile
- Efficacy in most cancers (equivalent)
- Mechanism of action

**Can You Switch Between Them?**

Cross-Resistance:
- Usually cross-resistant
- If one PD-1 inhibitor fails, the other unlikely to work
- Exception: Some patients respond after long break

Reasons to Switch:
- Insurance coverage issues
- Availability/access
- Participation in clinical trial
- Side effect profile (rare individual differences)

**Questions for Your Oncologist**

- Is my cancer approved for both drugs?
- Which do you recommend for my situation?
- Does my cancer have biomarkers favoring one vs. other?
- What's your experience with each drug?
- What's the dosing schedule?
- Does my insurance cover both?

**Bottom Line**

For Most Patients: Choice between Keytruda and OPDIVO should be based on:
1. FDA approval for your specific cancer
2. Clinical trial data for your situation
3. Dosing convenience preference
4. Your oncologist's recommendation
5. Insurance coverage

Both Are Excellent: You can't go wrong with either drug when both are appropriate for your cancer. They represent the greatest advances in cancer treatment in decades.

The "best" PD-1 inhibitor is the one that's approved for your cancer type and accessible to you.

Our team can help you access either Keytruda or OPDIVO and navigate insurance coverage.