IND227
Trial question
What is the role of the addition of pembrolizumab to standard platinum-pemetrexed chemotherapy in patients with untreated advanced malignant pleural mesothelioma?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
24.0% female
76.0% male
N = 440
440 patients (107 female, 333 male).
Inclusion criteria: adult patients with previously untreated advanced malignant pleural mesothelioma.
Key exclusion criteria: untreated CNS metastases; pneumonitis; receipt of corticosteroids equivalent to > 10 mg/day of prednisone within 7 days before the first dose of study treatment; concurrent serious illness or cancer.
Interventions
N=222 pembrolizumab plus chemotherapy (IV cisplatin 75 mg/m² or carboplatin with pemetrexed 500 mg/m² every 3 weeks for up to 6 cycles, with IV pembrolizumab 200 mg every 3 weeks for up to 2 years).
N=218 chemotherapy alone (IV cisplatin 75 mg/m² or carboplatin with pemetrexed 500 mg/m² every 3 weeks for up to 6 cycles).
Primary outcome
Median overall survival
17.3 months
16.1 months
17.3 months
13.0 months
8.7 months
4.3 months
0.0 months
Pembrolizumab plus
chemotherapy
Chemotherapy
alone
Significant
increase ▲
Significant increase in median overall survival (17.3 months vs. 16.1 months; HR 1.27, 95% CI 1.02 to 1.56).
Secondary outcomes
Significant increase in median progression-free survival (7.13 months vs. 7.16 months; HR 1.25, 95% CI 1.01 to 1.54).
Significant increase in objective response rate (62% vs. 38%; OR 2.7, 95% CI 1.8 to 4).
No significant difference in duration of complete or partial response (5.8 months vs. 5.5 months; AD 0.3 months, 95% CI -0.14 to 0.74).
Safety outcomes
No significant difference in grade 5 adverse events.
Conclusion
In adult patients with previously untreated advanced malignant pleural mesothelioma, pembrolizumab plus chemotherapy was superior to chemotherapy alone with respect to median overall survival.
Reference
Nicholas J Vogelzang, James J Rusthoven, James Symanowski et al. Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma. J Clin Oncol. 2023 Apr 20;41(12):2125-2133.
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