Platinum-doublet in MPM
Trial question
What is the role of pemetrexed in combination with cisplatin in patients with malignant pleural mesothelioma?
Study design
Multi-center
Single blinded
RCT
Population
Characteristics of study participants
19.0% female
81.0% male
N = 448
448 patients (83 female, 365 male).
Inclusion criteria: adult patients with malignant pleural mesothelioma ineligible for curative surgery.
Key exclusion criteria: prior chemotherapy; second primary malignancy; brain metastases; unable to interrupt NSAIDs.
Interventions
N=226 pemetrexed plus cisplatin (IV pemetrexed 500 mg/m² and cisplatin 75 mg/m² on day 1 every 3 weeks).
N=222 cisplatin alone (IV cisplatin 75 mg/m² on day 1 every 3 weeks).
Primary outcome
Median survival time
12.1 months
9.3 months
12.1 months
9.1 months
6.0 months
3.0 months
0.0 months
Pemetrexed plus
cisplatin
Cisplatin
alone
Significant
increase ▲
Significant increase in median survival time (12.1 months vs. 9.3 months; HR 1.3, 95% CI 0.2 to 2.4).
Secondary outcomes
Significantly longer median time to progression (5.7 months vs. 3.9 months; HR 1.47, 95% CI 0.6 to 2.34).
Significant increase in response rate (41.3% vs. 16.7%; AD 24.6%, 95% CI 12.31 to 36.89).
Significant increase in survival at 1 year (50.3% vs. 38%; AD 12.3%, 95% CI 2.7 to 21.9).
Safety outcomes
No significant differences in fatigue, vomiting, anorexia, febrile neutropenia, infection, and rash.
Significant differences in hematologic laboratory toxicity (56.2% vs. 3.2%), nausea (14.6% vs. 6.3%), dehydration (4.0% vs. 0.5%), and diarrhea (4.4% vs. 0%).
Conclusion
In adult patients with malignant pleural mesothelioma ineligible for curative surgery, pemetrexed plus cisplatin was superior to cisplatin alone with respect to median survival time.
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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