Key Findings
| Metric | Result |
|---|---|
| Median overall survival | 28.6 months |
| Average mesothelioma survival | 18 months |
| Survival improvement | +10.6 months (59%) |
| Patients completing surgery | 80%+ |
| Recurrence-free at follow-up | 36% |
A first-of-its-kind clinical trial from Johns Hopkins has demonstrated that combining immunotherapy before and after surgery can extend mesothelioma survival by nearly 60% compared to historical averages. The results, published in Nature Medicine in September 2025, offer new hope for patients with operable disease.
The Trial Design
The phase 2 trial, designed by Joshua Reuss, M.D., during his fellowship at the Johns Hopkins Kimmel Cancer Center, tested a novel approach: giving immunotherapy both before (neoadjuvant) and after (adjuvant) surgical removal of mesothelioma tumors.
Treatment Protocol
Patients received:
- Neoadjuvant phase: Nivolumab plus ipilimumab before surgery
- Surgery: Pleurectomy/decortication or extrapleural pneumonectomy
- Adjuvant phase: Continued immunotherapy after recovery
This “sandwich” approach aims to shrink tumors before surgery, then eliminate any remaining cancer cells afterward.
Survival Results
The combination immunotherapy arm achieved remarkable outcomes:
| Outcome | Combination (Nivo+Ipi) | Historical Average |
|---|---|---|
| Median overall survival | 28.6 months | 18 months |
| Alive and recurrence-free | 36% | ~15% |
| Surgical completion rate | >80% | Variable |
The 28.6-month median survival represents a 59% improvement over the typical 18-month survival for mesothelioma patients.
Liquid Biopsy Breakthrough
Perhaps equally important, the trial demonstrated that circulating tumor DNA (ctDNA) testing, a type of “liquid biopsy”, could predict which patients would benefit most.
ctDNA Findings
- Patients with undetectable ctDNA after neoadjuvant treatment had significantly longer survival
- A 95%+ drop in ctDNA during treatment predicted better outcomes
- Persistent ctDNA signaled early disease progression, even when imaging looked stable
This molecular monitoring could help doctors identify patients who need more aggressive treatment or different approaches.
Why This Matters for Patients
For Surgical Candidates
If you have operable mesothelioma, this trial suggests asking your oncologist about:
- Neoadjuvant immunotherapy before surgery
- ctDNA monitoring to track treatment response
- Adjuvant immunotherapy after surgery
Not all cancer centers offer this approach yet, but the Hopkins data may accelerate adoption.
Current Standard of Care
For comparison, current first-line treatments for unresectable mesothelioma include:
| Treatment | Median Survival | FDA Approved |
|---|---|---|
| Opdivo + Yervoy | 18.1 months | Oct 2020 |
| Chemotherapy (pem/cis) | 12-14 months | 2004 |
| Hopkins trial (surgery + IO) | 28.6 months | Trial only |
The Hopkins approach achieved the longest survival reported in a mesothelioma trial to date, though it applies only to patients whose tumors can be surgically removed.
The Researchers
The trial was led by researchers at Johns Hopkins Kimmel Cancer Center:
- Joshua Reuss, M.D.: Trial designer, now at Georgetown Lombardi
- Results presented at the 2025 World Conference on Lung Cancer (Barcelona)
- Published simultaneously in Nature Medicine
Limitations
Important caveats:
- Small sample size: Phase 2 trials involve fewer patients than Phase 3
- Selected population: Only patients with resectable tumors were eligible
- Single-arm comparison: Results compared to historical data, not a randomized control group
- Access: This approach requires specialized thoracic surgery expertise
What Comes Next
Based on these results, researchers are planning:
- Larger Phase 3 trials to confirm findings
- Studies combining this approach with other treatments
- Expanded ctDNA monitoring protocols
For patients with operable mesothelioma, the Hopkins trial represents a potential new treatment paradigm that dramatically extends survival.
If you have operable mesothelioma, ask your oncologist about neoadjuvant immunotherapy before surgery, ctDNA monitoring to track response, and adjuvant immunotherapy after surgery. Not all cancer centers offer this approach yet, but the Hopkins data may accelerate adoption.
What is neoadjuvant immunotherapy?▼
Neoadjuvant therapy is treatment given before surgery. In this trial, patients received nivolumab plus ipilimumab before surgical tumor removal, then continued immunotherapy afterward. This “sandwich” approach aims to shrink tumors before surgery and eliminate remaining cancer cells after.
How does this compare to standard treatment?▼
The 28.6-month median survival is 59% longer than the typical 18-month survival for mesothelioma patients. It’s also significantly longer than the 18.1 months achieved with Opdivo + Yervoy alone (without surgery) in the FDA approval trial.
What is ctDNA and why does it matter?▼
Circulating tumor DNA (ctDNA) is cancer DNA that can be detected in blood samples—a “liquid biopsy.” The Hopkins trial found that patients with undetectable ctDNA after treatment had significantly longer survival. This molecular monitoring could help identify patients who need different treatment approaches.
Who is eligible for this treatment approach?▼
This approach applies only to patients with surgically resectable (operable) mesothelioma—not all patients qualify. It requires specialized thoracic surgery expertise. Ask your oncologist whether you might be a candidate and if there are trials or treatment centers offering this approach.