On September 17, 2024, the Food and Drug Administration authorized pembrolizumab (Keytruda, Merck) in conjunction with pemetrexed and platinum-based chemotherapy as the initial treatment for unresectable advanced or metastatic malignant pleural mesothelioma (MPM).
Effectiveness and Safety
The efficacy was examined in KEYNOTE-483 (NCT02784171), a randomized, open-label trial involving patients with unresectable advanced or metastatic malignant pleural mesothelioma (MPM) who had not had prior systemic therapy for advanced or metastatic illness. Patients were randomized (1:1) to receive either pembrolizumab for a maximum of 2 years in conjunction with pemetrexed and platinum-based chemotherapy for up to 6 cycles (n=222) or pemetrexed and platinum-based chemotherapy alone for up to 6 cycles (n=218).
The primary effectiveness endpoint was overall survival (OS). The supplementary efficacy outcome variables included progression-free survival (PFS), objective response rate (ORR), and duration of response (DoR), evaluated by blinded independent central review in accordance with modified RECIST 1.1 for mesothelioma.
The trial exhibited a statistically significant enhancement in overall survival for individuals administered pembrolizumab in conjunction with chemotherapy, in contrast to those who got chemotherapy solely. The median overall survival (OS) was 17.3 months (95% confidence interval [CI]: 14.4, 21.3) compared to 16.1 months (95% CI: 13.1, 18.2), with a hazard ratio (HR) of 0.79 (95% CI: 0.64, 0.98; p=0.0162).
The median progression-free survival (PFS) was 7.1 months (95% CI: 6.9, 8.1) for the pembrolizumab plus chemotherapy group and 7.1 months (95% CI: 6.8, 7.7) for the chemotherapy alone group, respectively (HR 0.80 [95% CI: 0.65, 0.99]; p=0.0194).
The confirmed overall response rate (ORR) was 52% (95% confidence interval: 45.5, 59.0) in the pembrolizumab plus chemotherapy group and 29% (95% confidence interval: 23.0, 35.4) in the chemotherapy-only group. The median duration of response (DoR) was 6.9 months (95% confidence interval: 5.8, 8.3) and 6.8 months (95% confidence interval: 5.5, 8.5), respectively.
Adverse effects in people with MPM were comparable to those in those taking pembrolizumab in conjunction with pemetrexed and platinum-based chemotherapy. Refer to the prescription information for comprehensive details.
The advised dosage of pembrolizumab is 200 mg every three weeks or 400 mg every six weeks, continuing until disease progression or intolerable toxicity, for a maximum duration of two years.
Dr. Nishant Mittal is a highly accomplished researcher with over 13 years of experience in the fields of cardiovascular biology and cancer research. His career is marked by significant contributions to stem cell biology, developmental biology, and innovative research techniques.
Research Highlights
Dr. Mittal's research has focused on several key areas:
1) Cardiovascular Development and Regeneration: He studied coronary vessel development and regeneration using zebrafish models1.
2) Cancer Biology: At Dartmouth College, he developed zebrafish models for studying tumor heterogeneity and clonal evolution in pancreatic cancer.
3) Developmental Biology: His doctoral work at Keio University involved identifying and characterizing medaka fish mutants with cardiovascular defects.
4) Stem Cell Research: He investigated the effects of folic acid on mouse embryonic stem cells and worked on cryopreservation techniques for hematopoietic stem cells.
Publications and Presentations
Dr. Mittal has authored several peer-reviewed publications in reputable journals such as Scientific Reports, Cardiovascular Research, and Disease Models & Mechanisms1. He has also presented his research at numerous international conferences, including the Stanford-Weill Cornell Cardiovascular Research Symposium and the Weinstein Cardiovascular Development Conference.
In summary, Dr. Nishant Mittal is a dedicated and accomplished researcher with a strong track record in cardiovascular and cancer biology, demonstrating expertise in various model systems and a commitment to advancing scientific knowledge through innovative research approaches.
