FDA D.I.S.C.O. Burst Edition: FDA approval of Keytruda (pembrolizumab) for unresectable advanced or metastatic malignant pleural mesothelioma
Regulatory approval: On Sept 17, 2024, the FDA approved pembrolizumab (Keytruda) with pemetrexed and platinum chemotherapy as first-line treatment for unresectable advanced or metastatic malignant pleural mesothelioma. The decision was based on KEYNOTE-483, a randomized open-label trial in patients without prior systemic therapy for advanced/metastatic disease, showing a statistically significant overall survival improvement versus chemotherapy alone (median OS 17.3 vs 16.1 months).
FDA approval (Sept 17, 2024): pembrolizumab + pemetrexed/platinum for malignant pleural mesothelioma
The FDA approved pembrolizumab (Keytruda) in combination with pemetrexed and platinum chemotherapy as first-line treatment for unresectable advanced or metastatic malignant pleural mesothelioma (MPM) (Sept 17, 2024). This update was reported via the FDA D.I.S.C.O. Burst Edition.
Supporting evidence: KEYNOTE-483
KEYNOTE-483 was a randomized, open-label trial in patients with unresectable advanced or metastatic MPM and no prior systemic therapy for advanced/metastatic disease. Patients were randomized 1:1 to:
- Pembrolizumab (up to 2 years) + pemetrexed/platinum (up to 6 cycles), or
- Pemetrexed/platinum alone (up to 6 cycles).
Primary endpoint: overall survival (OS). Additional endpoints included progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) assessed by blinded independent central review per modified RECIST 1.1 for mesothelioma.
Results:
- OS: statistically significant improvement with pembrolizumab + chemotherapy; median 17.3 vs 16.1 months.
- PFS: median 7.1 vs 7.1 months.
- Confirmed ORR: 52% vs 29%.
- Median DOR: 6.9 vs 6.8 months.
Safety: adverse reactions in MPM were reported as similar to those seen with pembrolizumab plus pemetrexed/platinum chemotherapy; full details are in prescribing information.
The review was conducted under Project Orbis; reviews at other agencies were stated as ongoing.