Key Trial Results
| Outcome | Nivolumab | Placebo | Improvement |
|---|---|---|---|
| Median overall survival | 9.2 months | 6.6 months | +40% |
| 1-year survival | 39.5% | 26.9% | +12.6 percentage points |
| Hazard ratio (death) | 0.72 | : | 28% risk reduction |
| Disease control rate | 44.6% | 23.8% | Nearly doubled |
The CONFIRM trial was a landmark Phase 3 study that established nivolumab (Opdivo) as an effective option for patients with relapsed mesothelioma who had progressed on prior chemotherapy. Published in The Lancet Oncology, this trial provides crucial data about who benefits most from immunotherapy.
Why CONFIRM Mattered
The Treatment Gap
Before CONFIRM, patients whose mesothelioma returned after chemotherapy had limited options:
| Treatment Line | Standard Options | Response Rate |
|---|---|---|
| First-line | Pemetrexed + platinum | ~40% |
| Second-line | No standard | Variable |
| Relapsed | Clinical trials only | Unknown |
CONFIRM addressed this critical gap by testing whether immunotherapy could help patients who had exhausted standard chemotherapy.
Trial Design
| Characteristic | Detail |
|---|---|
| Phase | 3 (randomized, double-blind) |
| Patients | 332 |
| Randomization | 2:1 nivolumab:placebo |
| Population | Relapsed after 1-2 prior lines |
| Primary endpoint | Overall survival |
| Location | UK (multicenter) |
Detailed Results
Survival Benefits
Nivolumab demonstrated clear survival advantages:
| Timepoint | Nivolumab | Placebo | Benefit |
|---|---|---|---|
| Median OS | 9.2 months | 6.6 months | +2.6 months |
| 6-month OS | 63.7% | 55.4% | +8.3% |
| 1-year OS | 39.5% | 26.9% | +12.6% |
The hazard ratio of 0.72 means nivolumab reduced the risk of death by 28% compared to placebo.
Response Rates
| Response | Nivolumab | Placebo |
|---|---|---|
| Objective response rate | 8.9% | 0.5% |
| Disease control rate | 44.6% | 23.8% |
| Progressive disease | 52.9% | 75.2% |
While objective tumor shrinkage was modest (8.9%), the disease control rate, patients whose tumors didn’t grow, was nearly double that of placebo.
Biomarker Analysis: Who Benefits Most?
PD-L1 Expression
The trial explored whether PD-L1 levels on tumor cells predicted response:
| PD-L1 Status | Benefit with Nivolumab |
|---|---|
| PD-L1 1% or higher | Survival benefit observed |
| PD-L1 below 1% | Also showed benefit |
| PD-L1 unknown | Consistent with overall results |
Key finding: Unlike some other cancers, mesothelioma patients benefited from nivolumab regardless of PD-L1 status. This means PD-L1 testing alone shouldn’t determine treatment eligibility.
Unlike other cancers where PD-L1 expression guides immunotherapy decisions, CONFIRM showed mesothelioma patients benefited regardless of PD-L1 status. Don’t let a low PD-L1 result exclude you from considering immunotherapy.
Histological Subtype
| Cell Type | Nivolumab Benefit |
|---|---|
| Epithelioid | Yes |
| Non-epithelioid | Yes |
Both major histological subtypes showed survival benefits, though the trial was not powered to detect subgroup differences.
Other Exploratory Biomarkers
Researchers examined additional potential predictors:
| Biomarker | Finding |
|---|---|
| Tumor mutational burden | Higher TMB may predict response |
| BAP1 loss | May influence outcomes |
| NF2 alterations | Being studied |
| Inflammatory gene signatures | May predict benefit |
These exploratory analyses suggest that mesothelioma immunotherapy response may depend on multiple factors beyond PD-L1 expression.
Clinical Implications
What CONFIRM Means for Patients
- Immunotherapy works in relapsed mesothelioma: Provides a new treatment option
- PD-L1 testing isn’t required: Benefit seen regardless of PD-L1 status
- Durable responses possible: Some patients have prolonged benefit
- Manageable side effects: Most patients tolerated treatment well
Treatment Sequencing Considerations
| Scenario | Consideration |
|---|---|
| First relapse after chemo | Nivolumab is an option |
| Multiple prior treatments | May still respond |
| Epithelioid subtype | Expected to benefit |
| Non-epithelioid subtype | Also likely to benefit |
Safety Profile
| Adverse Event | Grade 3-4 (Nivolumab) | Grade 3-4 (Placebo) |
|---|---|---|
| Any treatment-related | 11.8% | 4.5% |
| Fatigue | 1.4% | 0% |
| Rash | 0.5% | 0% |
| Pneumonitis | 0.5% | 0% |
Immunotherapy-related adverse events were manageable, with most patients able to continue treatment.
Comparison to Other Immunotherapy Data
CONFIRM vs CheckMate-743
| Trial | Setting | Drugs | Median OS |
|---|---|---|---|
| CONFIRM | Relapsed | Nivolumab alone | 9.2 months |
| CheckMate-743 | First-line | Nivo + Ipi | 18.1 months |
CheckMate-743 tested combination immunotherapy in previously untreated patients, while CONFIRM tested single-agent immunotherapy in the relapsed setting.
Building the Evidence Base
Together, these trials establish immunotherapy as a treatment option across multiple settings:
| Setting | Evidence | Regimen |
|---|---|---|
| First-line | CheckMate-743 | Nivo + Ipi |
| Relapsed | CONFIRM | Nivolumab |
| Perioperative | Ongoing trials | Various combinations |
Current Treatment Landscape
Where Nivolumab Fits
Based on CONFIRM and other data, nivolumab is now an option for:
- Patients who progress after platinum-based chemotherapy
- Those unable to receive combination immunotherapy
- Selected patients in clinical trials
Limitations
- Not FDA-approved specifically for mesothelioma based on CONFIRM
- CheckMate-743 (Opdivo + Yervoy) is the approved first-line regimen
- Access may vary by insurance and geography
What This Means for You
If You Have Relapsed Mesothelioma
- Ask about immunotherapy options: Discuss whether nivolumab or combination immunotherapy is appropriate
- Don’t rely solely on PD-L1 testing: Benefits occur regardless of PD-L1 status
- Consider clinical trials: Many trials are building on CONFIRM results
- Discuss biomarker testing: Comprehensive profiling may identify other options
Questions for Your Oncologist
- Am I a candidate for immunotherapy?
- Should I have biomarker testing beyond PD-L1?
- What clinical trials are available for relapsed mesothelioma?
- What are the expected benefits and risks for my specific situation?
The Future of Biomarker-Guided Treatment
CONFIRM established immunotherapy as effective in relapsed mesothelioma, but the search for better predictive biomarkers continues:
| Research Direction | Goal |
|---|---|
| Multi-gene signatures | Predict responders |
| Tumor microenvironment analysis | Understand resistance |
| Circulating biomarkers | Monitor response |
| Combination strategies | Overcome resistance |
As we learn more about mesothelioma biology, treatment selection will become increasingly personalized.
What did the CONFIRM trial prove?▼
CONFIRM was a Phase 3 trial of 332 patients that established nivolumab as effective for relapsed mesothelioma. It showed a 40% improvement in survival (9.2 vs 6.6 months) and a 28% reduction in risk of death compared to placebo. This addressed a critical treatment gap for patients who had progressed on chemotherapy.
Does PD-L1 testing predict who will respond?▼
No—and this is a key finding. Unlike some other cancers, mesothelioma patients benefited from nivolumab regardless of PD-L1 status. Patients with low PD-L1 (below 1%) still showed benefit. This means PD-L1 testing alone shouldn’t determine treatment eligibility for mesothelioma patients.
How does CONFIRM relate to CheckMate-743?▼
They address different treatment settings. CheckMate-743 tested combination immunotherapy (nivolumab + ipilimumab) in previously untreated patients and showed 18.1 months median survival. CONFIRM tested single-agent nivolumab in relapsed patients. Together, they establish immunotherapy as an option across multiple treatment lines.
What questions should I ask my oncologist?▼
Ask: Am I a candidate for immunotherapy? Should I have biomarker testing beyond PD-L1? What clinical trials are available for relapsed mesothelioma? What are the expected benefits and risks for my specific situation? Don’t let a low PD-L1 result alone exclude you from considering immunotherapy.