(Pleural Mesothelioma) Cediranib Plus Pemetrexed Disodium Plus Cisplatin: Is It Effective?

• September 17, 2019
• 2 min read

On August 6, 2019, Dr. Anne S. Tsao published results in the Journal of Clinical Oncology from the SWOG S0905 Phase 2 clinical trial evaluating the efficacy and safety of combining the anti-VEGFR inhibitor Cediranib with pemetrexed disodium and cisplatin in unresectable, chemotherapy-naive malignant pleural mesothelioma patients.

The SWOG S0905 trial was a randomized Phase 2 study enrolling 92 patients with unresectable, chemotherapy-naive malignant pleural mesothelioma. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS) and objective response rate (ORR). Treatment was on a 21-day cycle:

• Cediranib group (N=45): Pemetrexed 500 mg/m² (Day 1) + Cisplatin 75 mg/m² (Day 1) + Cediranib 20 mg orally once daily (Days 1–21)
• Placebo group (N=47): Pemetrexed 500 mg/m² (Day 1) + Cisplatin 75 mg/m² (Day 1) + Placebo once daily (Days 1–21)

Background: Malignant pleural mesothelioma is a rare cancer with poor prognosis and limited treatment options. Systemic chemotherapy combined with VEGFR inhibitors was expected to enhance anti-tumor efficacy. This trial evaluated oral VEGFR inhibitor Cediranib combined with chemotherapy.

Patient Demographics:

Results at median follow-up of 31 months:

Primary endpoint median PFS: Cediranib 7.2 months vs. placebo 5.6 months — Cediranib improved disease progression risk by 29% (HR: 0.71).

Secondary endpoint median OS: Cediranib 10 months vs. placebo 8.5 months — Cediranib improved survival risk by 12%, but without statistical significance (HR: 0.88). ORR: Cediranib 50% vs. placebo 20% — statistically significant improvement.

Safety:

Overall adverse event incidence: Cediranib 100% vs. placebo 91%. Grade 3–4 adverse events: Cediranib 69% vs. placebo 57%. Higher rates in the Cediranib arm included: anorexia (51% vs. 38%), diarrhea (46.7% vs. 17%), epistaxis (13% vs. 0%), muscle atrophy (16% vs. 9%), hypertension (44% vs. 15%), nausea (76% vs. 66%), peripheral neuropathy (20% vs. 11%), weight loss (36% vs. 21%), myelosuppression (44% vs. 30%).

Conclusion: Based on the SWOG S0905 trial results, Dr. Tsao concluded that Cediranib combined with pemetrexed disodium and cisplatin improved PFS and ORR in unresectable, chemotherapy-naive malignant pleural mesothelioma patients.

Disclaimer: Medical Supporter translates overseas clinical trial data for informational purposes only. Please consult your healthcare provider for medical decisions.

Source: Phase II Trial of Cediranib in Combination With Cisplatin and Pemetrexed in Chemotherapy-Naïve Patients With Unresectable Malignant Pleural Mesothelioma (SWOG S0905). J Clin Oncol. 2019 Aug 6: JCO1900269.

Pleural Mesothelioma

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