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Secondary malignant neoplasms, progression-free survival and overall survival in patients treated for Hodgkin lymphoma: a systematic review and meta-analysis of randomized clinical trials.

ABSTRACT: Treatment intensification to maximize disease control and reduced intensity approaches to minimize the risk of late sequelae have been evaluated in newly diagnosed Hodgkin lymphoma. The influence of these interventions on the risk of secondary malignant neoplasms, progression-free survival and overall survival is reported in the meta-analysis herein, based on individual patient data from 9498 patients treated within 16 randomized controlled trials for newly diagnosed Hodgkin lymphoma between 1984 and 2007. Secondary malignant neoplasms were meta-analyzed using Peto's method as time-to-event outcomes. For progression-free and overall survival, hazard ratios derived from each trial using Cox regression were combined by inverse-variance weighting. Five study questions (combined-modality treatment vs. chemotherapy alone; more extended vs. involved-field radiotherapy; radiation at higher doses vs. radiation at 20 Gy; more vs. fewer cycles of the same chemotherapy protocol; standard-dose chemotherapy vs. intensified chemotherapy) were investigated. After a median follow-up of 7.4 years, dose-intensified chemotherapy resulted in better progression-free survival rates (P=0.007) as compared with standard-dose chemotherapy, but was associated with an increased risk of therapy-related acute myeloid leukemia/myelodysplastic syndromes (P=0.0028). No progression-free or overall survival differences were observed between combined-modality treatment and chemotherapy alone, but more secondary malignant neoplasms were seen after combined-modality treatment (P=0.010). For the remaining three study questions, outcomes and secondary malignancy rates did not differ significantly between treatment strategies. The results of this meta-analysis help to weigh up efficacy and secondary malignancy risk for the choice of first-line treatment for Hodgkin lymphoma patients. However, final conclusions regarding secondary solid tumors require longer follow-up.

SUBMITTER: Eichenauer DA

PROVIDER: S-EPMC5622859 | biostudies-other | 2017 Oct

REPOSITORIES: biostudies-other

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Secondary malignant neoplasms, progression-free survival and overall survival in patients treated for Hodgkin lymphoma: a systematic review and meta-analysis of randomized clinical trials.

Eichenauer Dennis A DA Becker Ingrid I Monsef Ina I Chadwick Nicholas N de Sanctis Vitaliana V Federico Massimo M Fortpied Catherine C Gianni Alessandro M AM Henry-Amar Michel M Hoskin Peter P Johnson Peter P Luminari Stefano S Bellei Monica M Pulsoni Alessandro A Sydes Matthew R MR Valagussa Pinuccia P Viviani Simonetta S Engert Andreas A Franklin Jeremy J

Haematologica 20170914 10

Treatment intensification to maximize disease control and reduced intensity approaches to minimize the risk of late sequelae have been evaluated in newly diagnosed Hodgkin lymphoma. The influence of these interventions on the risk of secondary malignant neoplasms, progression-free survival and overall survival is reported in the meta-analysis herein, based on individual patient data from 9498 patients treated within 16 randomized controlled trials for newly diagnosed Hodgkin lymphoma between 198 ...[more]

PMID: 28912173

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Project description:Introduction: With a gap in a full understanding of the mechanisms by which survival is extended for patients with cancer who are treated with novel biologic and targeted agents, there is the risk that discordant progression-free and overall survival outcomes are observed due to poor clinical trial design or biases in the interpretation of data. This study was designed to examine the role of study quality and design on the outcomes observed with biologic and targeted agents. Methods: A review of studies in clinicaltrials.gov supplemented with a literature review in OVID Medline was conducted to identify all randomized trials of a biologic/targeted agent versus a non-biologic/targeted comparator in oncology that report both median overall and progression-free survival outcomes. Details of the study, design, population, drugs, and outcomes were extracted. Study quality was evaluated using the PEDro scale. Data were summarized using SPSS 22.0.0.0. Results: A total of 192 unique studies of 206 pairwise comparisons between a biologic/targeted and comparator were identified. The average absolute magnitude of post-progression survival (difference between OS and PFS) was 9.7 months for biologic/targeted therapy and 9.8 for the comparator. A total of 64 comparisons (31.1%) showed an increase in OS and decrease in PFS, or vice versa, and 25 (12.1%) showed a magnitude of more than 4 months difference between the delta of OS and delta of PFS between the biologic/targeted and comparator arms. Average study quality was high overall (7.7/10), and was comparable for studies with directional differences (7.2/10) as well as for those with the greatest magnitude in post-progression survival (7.4/10). Conclusion: This review and analysis specifically examined small PFS benefit with large OS benefit as well as small OS benefit with large PFS benefit, including differences in direction of PFS and OS outcomes. No evidence was identified that these are the result of poor study design, but may rather be due to the mechanism of action, specific disease, and population under study. Further work is needed to understand the mechanism of action of novel biologic/targeted agents to better understand their interaction with the tumor microenvironment.

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Secondary malignant neoplasms, progression-free survival and overall survival in patients treated for Hodgkin lymphoma: a systematic review and meta-analysis of randomized clinical trials.

Publications

Secondary malignant neoplasms, progression-free survival and overall survival in patients treated for Hodgkin lymphoma: a systematic review and meta-analysis of randomized clinical trials.

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