Randomized Study of Maintenance Pemetrexed Versus Observation for Treatment of Malignant Pleural Mesothelioma: CALGB 30901.

Abstract

BACKGROUND:

The role of maintenance therapy for malignant pleural mesothelioma (MPM) is unknown. We performed a randomized phase II trial to determine if continuation of pemetrexed after first-line pemetrexed and platinum would improve progression-free survival (PFS).

PATIENTS AND METHODS:

Eligible patients with unresectable MPM, without disease progression following 4 to 6 cycles of pemetrexed and platinum were randomized 1:1 to observation or continuation of pemetrexed until progression, stratified by number of cycles (< 6 or 6), cis- or carboplatin containing regimen, and histology. Study size was calculated based on the assumption that observation would produce a median PFS of 3 months and pemetrexed would yield median PFS of 6 months.

RESULTS:

A total of 72 patients were registered from December 2010 to June 2016. The study closed early after 53 patients were randomized; 49 eligible (22 on the observation arm and 27 on the pemetrexed arm) were included in the analysis. The median PFS was 3 months (95% confidence interval [CI], 2.6-11.9 months) on observation and 3.4 months (95% CI, 2.8-9.8 months) on pemetrexed (hazard ratio [HR], 0.99; 95% CI, 0.51-1.90; P = .9733). The median overall survival (OS) was 11.8 months (95% CI, 9.3-28.7 months) for observation, and 16.3 months (95% CI, 10.5-26.0 months) for pemetrexed (HR, 0.86; 95% CI, 0.44-1.71; P = .6737). Grade 3 or 4 toxicities on the pemetrexed arm included anemia (8%), lymphopenia (8%), neutropenia (4%), and fatigue (4%). A higher baseline level of soluble mesothelin-related peptide was associated with worse PFS (HR, 1.86; 95% CI, 1.00-3.46; P = .049).

CONCLUSION:

Maintenance pemetrexed following initial pemetrexed and platinum chemotherapy does not improve PFS in patients with MPM.

• Authors: Arkadiusz Z Dudek, Xiaofei Wang, Lin Gu, Stephanie Duong, Thomas E Stinchcombe, Robert Kratzke, Hossein Borghaei, Everett E Vokes, Hedy L Kindler
• Journal: Clinical lung cancer (Clin Lung Cancer) Vol. 21 Issue 6 Pg. 553-561.e1 (11 2020) ISSN: 1938-0690 [Electronic] United States
• PMID: 32727707 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Pemetrexed
• Carboplatin
• Cisplatin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carboplatin (administration & dosage)
• Cisplatin (administration & dosage)
• Female
• Follow-Up Studies
• Humans
• Maintenance Chemotherapy (mortality)
• Male
• Mesothelioma, Malignant (drug therapy, metabolism, pathology)
• Middle Aged
• Observation
• Pemetrexed (administration & dosage)
• Pleural Neoplasms (drug therapy, metabolism, pathology)
• Prognosis
• Retrospective Studies
• Survival Rate