Opdivo (nivolumab) and Keytruda (pembrolizumab) are two of the most widely used and recognizable names in cancer immunotherapy. As programmed death-1 (PD-1) inhibitors, they both work by unleashing the body's immune system to attack and destroy cancer cells. Given their similar mechanism of action, the question of whether a patient can switch from Opdivo to Keytruda is complex and depends on specific clinical factors rather than a simple substitution for better results. The decision rests on the careful judgment of an oncologist, taking into account the patient's individual condition, the cancer type, and their treatment history.
Understanding Opdivo and Keytruda: The PD-1 Inhibitors
Opdivo and Keytruda belong to a class of drugs known as immune checkpoint inhibitors (ICIs). Their mechanism of action involves blocking the PD-1 protein on T-cells. Cancer cells often overexpress a corresponding ligand, PD-L1, which binds to PD-1 and effectively 'hides' the cancer from the immune system. By blocking this pathway, both drugs help restore the immune system's ability to recognize and target cancer cells.
Despite this fundamental similarity, key differences exist, such as different active ingredients (nivolumab vs. pembrolizumab), varying dosing schedules, and distinct FDA-approved indications. These differences, alongside a patient's unique response and side effect profile, are what an oncologist weighs when considering a switch.
Primary Reasons to Switch from Opdivo to Keytruda
Managing Severe Side Effects
The most common and clinically supported reason for a physician to consider switching from Opdivo to Keytruda is a severe or persistent immune-related adverse event (irAE). While both medications can cause irAEs, including colitis, pneumonitis, or endocrinopathies, the specific side effect profile, frequency, and severity can vary between the two. In some instances, a patient may experience a specific irAE or an infusion-related reaction that is intolerable or unmanageable with one drug. Case reports have documented successful switches. For example, one report detailed a patient with heart inflammation (myocarditis) that resolved after switching from Keytruda to Opdivo, and another a patient with an infusion reaction who successfully switched to Keytruda.
Exploring Treatment Options After Disease Progression
Switching from one PD-1 inhibitor to another after the initial drug has failed to control the cancer (disease progression) is generally not standard practice. The rationale is that if the PD-1 blockade strategy was unsuccessful with one drug, it is unlikely to be effective with another that works via the same mechanism. However, some smaller case series and studies have investigated this strategy in select patients, particularly those with advanced non-small cell lung cancer (NSCLC) who have limited treatment options after initial ICI progression. These studies are not supported by randomized clinical trial data and require careful consideration, and current guidelines do not recommend this approach. In such cases, other treatment strategies, like chemotherapy, are typically preferred.
Unique Approved Indications or Tumor Biomarkers
Keytruda has been granted FDA approval for a wider range of cancers than Opdivo. Furthermore, Keytruda has specific approvals for cancers with certain genetic characteristics, such as high tumor mutational burden (TMB-H), microsatellite-instability high (MSI-H), or deficient mismatch repair (dMMR). Opdivo's indication for MSI-H/dMMR is narrower, applying only to colorectal cancer. If a patient's tumor testing reveals a specific biomarker for which Keytruda has a proven indication, but Opdivo does not, a switch may be a valid option. This is especially true for second-line or later treatment settings when other therapies have been exhausted.
Key Differences: Opdivo vs. Keytruda
To understand the basis for a potential switch, it is helpful to compare the two medications directly:
| Feature | Opdivo (Nivolumab) | Keytruda (Pembrolizumab) |
|---|---|---|
| Active Ingredient | Nivolumab | Pembrolizumab |
| Drug Class | Immune Checkpoint Inhibitor (PD-1) | Immune Checkpoint Inhibitor (PD-1) |
| Dosing Schedule | Every 2, 3, or 4 weeks (IV infusion) | Every 3 or 6 weeks (IV infusion) |
| Combinations | Often used in combination with another ICI, Yervoy (ipilimumab) | Not typically combined with other ICIs |
| FDA-Approved Indications | Treats a growing list of cancers (approx. 20 specific uses) | Treats a broader list of cancers (approx. 40 specific uses) |
| Biomarker-Driven Indications | Narrower approvals (e.g., MSI-H/dMMR colorectal cancer) | Broader approvals (MSI-H, dMMR, TMB-H across multiple cancers) |
| Notable Side Effect Differences | Can be associated with more frequent and severe overall side effects in some studies; more back/joint pain, headaches, respiratory infections reported | More likely to cause low thyroid function in some studies |
The Decision-Making Process for Switching
When a switch is being considered, the oncologist performs a thorough evaluation of the patient's medical history, the reason for discontinuing the first drug, and the goals of the new treatment. This process involves:
- Reviewing Side Effects: Detailed assessment of the irAE or infusion reaction that occurred with Opdivo to determine if Keytruda might be better tolerated.
- Evaluating Disease Status: Assessing whether the cancer has progressed. If it has, alternative non-PD-1 inhibitor therapies might be more appropriate.
- Biomarker Analysis: Examining tumor biomarker status (e.g., MSI-H, TMB-H) to see if Keytruda has a specific indication that Opdivo does not.
- Considering Patient Preference: Some patients may prefer the longer dosing interval of Keytruda, which can reduce the number of clinic visits.
- Assessing Patient Health and Performance Status: Evaluating the overall health of the patient, which might impact their ability to tolerate another immunotherapy or alternative treatments.
The Importance of Monitoring
If a switch is made, the patient will be closely monitored for any new or recurring side effects. The risk of repeating a severe irAE is a key concern, though some studies suggest that manageable irAEs during the first ICI treatment are not always repeated with a switch. In many cases, managing a severe irAE on the first drug involves a temporary stop in treatment and the use of steroids or immunosuppressants before resuming treatment or considering a switch.
Conclusion
While switching from Opdivo to Keytruda is possible, it is not a routine or interchangeable strategy. Given their similar mechanism, a switch is generally not recommended solely for lack of efficacy. However, for a patient experiencing intolerable immune-related side effects on Opdivo, switching to Keytruda under the guidance of an oncologist can be a viable treatment strategy. Additionally, in specific cases where Keytruda has a unique approved indication based on a patient's tumor characteristics, a switch may be medically appropriate. Ultimately, the decision should be made collaboratively between the patient and their oncology team after a thorough review of the patient's health and cancer status.
For more information on the differences between Opdivo and Keytruda, you can consult resources like GoodRx, which offers a useful comparison: https://www.goodrx.com/compare/keytruda-vs-opdivo.
Potential Reasons to Switch to a Different PD-1 Inhibitor
- Severe IrAEs: Switching due to unmanageable side effects like pneumonitis, colitis, or myocarditis.
- Infusion Reactions: Experiencing an allergic or infusion-related reaction to one drug but not the other.
- Differential Indications: Accessing treatment for a specific cancer or biomarker (e.g., TMB-H) where Keytruda has an approval that Opdivo does not.
- Access Issues: In rare cases, switching might be necessary due to limited access to a specific brand of anti-PD-1 antibodies.
- Alternative Dosing Schedule: Switching to a regimen with less frequent infusions, such as Keytruda's every 6-week option.
