The FDA has granted priority review to a new supplemental biologics license application (sBLA) for pembrolizumab (Keytruda) in combination with chemotherapy as a frontline treatment for patients with unresectable or metastatic malignant pleural mesothelioma. This decision is based on promising results from the pivotal phase 2/3 IND.227/KEYNOTE-483 trial.
Key Takeaways
- Priority Review: The FDA has accepted the sBLA for pembrolizumab plus chemotherapy, setting a target action date of September 25, 2024.
- Clinical Trial Results: The combination therapy showed a statistically significant improvement in overall survival (OS) and progression-free survival (PFS) compared to chemotherapy alone.
- Potential Impact: If approved, this treatment could offer new hope for patients with advanced malignant pleural mesothelioma, a disease often diagnosed at an advanced stage with limited treatment options.
Clinical Trial Insights
The IND.227/KEYNOTE-483 trial was a randomized, open-label phase 2/3 study that evaluated the efficacy of pembrolizumab combined with chemotherapy versus chemotherapy alone in patients with unresected advanced pleural mesothelioma. The primary endpoint was overall survival (OS), while secondary endpoints included progression-free survival (PFS) and objective response rate (ORR).
Trial Results
- Overall Survival (OS): The combination therapy led to a median OS of 17.3 months compared to 16.1 months for chemotherapy alone.
- Progression-Free Survival (PFS): The median PFS was 7.13 months for the combination therapy versus 7.16 months for chemotherapy alone.
- Objective Response Rate (ORR): Patients experienced a higher ORR with the combination therapy (62%) compared to chemotherapy alone (38%).
Patient Demographics and Eligibility
To be eligible for the trial, patients needed to meet specific criteria, including an ECOG performance status of 0 or 1, adequate hematologic, liver, and renal function, and measurable disease by modified RECIST criteria. Patients with prior systemic therapy in the advanced setting or more than 10 mg of prednisone daily were excluded.
Baseline Characteristics
- Gender: 74% male
- Race: 79% White
- ECOG Performance Status: 55% had a status of 1
- Median Age: 71 years (range, 33-87)
- Histological Subtype: 78% epithelioid
- PD-L1 Positive: 59%
Safety Profile
The safety profile of the combination therapy was consistent with previously reported studies. Common adverse reactions included fatigue, nausea, and rash. Serious adverse reactions were rare but included immune-mediated adverse reactions such as pneumonitis and colitis.
Future Implications
If approved, the combination of pembrolizumab and chemotherapy could become a new standard of care for patients with advanced malignant pleural mesothelioma. This would provide a significant advancement in the treatment of this aggressive cancer, offering improved survival outcomes and quality of life for patients.
Conclusion
The FDA’s priority review of pembrolizumab plus chemotherapy for advanced pleural mesothelioma marks a significant step forward in cancer treatment. With promising clinical trial results, this combination therapy has the potential to offer new hope to patients facing this challenging disease.
Sources
- FDA Grants Priority Review to Pembrolizumab Plus Chemotherapy for Advanced Pleural Mesothelioma, OncLive.
- FDA Prioritizes Keytruda Chemotherapy Mesothelioma Combo, Mesothelioma Center.
- FDA Grants Priority Review to Merck’s Application for KEYTRUDA® (pembrolizumab) Plus Chemotherapy as First-Line Treatment of Patients With Unresectable Advanced or Metastatic Malignant Pleural Mesothelioma, Yahoo Finance.
