Risk and benefit for umbrella trials in oncology: a systematic review and meta-analysis
Abstract Background Umbrella clinical trials in precision oncology are designed to tailor therapies to the specific genetic changes within a tumor. Little is known about the risk/benefit ratio for umbrella clinical trials. The aim of our systematic review with meta-analysis was to evaluate the effic...
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | BMC Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12916-022-02420-2 |
| _version_ | 1811323731461537792 |
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| author | Karolina Strzebonska Mateusz Blukacz Mateusz T. Wasylewski Maciej Polak Bishal Gyawali Marcin Waligora |
| author_facet | Karolina Strzebonska Mateusz Blukacz Mateusz T. Wasylewski Maciej Polak Bishal Gyawali Marcin Waligora |
| author_sort | Karolina Strzebonska |
| collection | DOAJ |
| description | Abstract Background Umbrella clinical trials in precision oncology are designed to tailor therapies to the specific genetic changes within a tumor. Little is known about the risk/benefit ratio for umbrella clinical trials. The aim of our systematic review with meta-analysis was to evaluate the efficacy and safety profiles in cancer umbrella trials testing targeted drugs or a combination of targeted therapy with chemotherapy. Methods Our study was prospectively registered in PROSPERO (CRD42020171494). We searched Embase and PubMed for cancer umbrella trials testing targeted agents or a combination of targeted therapies with chemotherapy. We included solid tumor studies published between 1 January 2006 and 7 October 2019. We measured the risk using drug-related grade 3 or higher adverse events (AEs), and the benefit by objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). When possible, data were meta-analyzed. Results Of the 6207 records identified, we included 31 sub-trials or arms of nine umbrella trials (N = 1637). The pooled overall ORR was 17.7% (95% confidence interval [CI] 9.5–25.9). The ORR for targeted therapies in the experimental arms was significantly lower than the ORR for a combination of targeted therapy drugs with chemotherapy: 13.3% vs 39.0%; p = 0.005. The median PFS was 2.4 months (95% CI 1.9–2.9), and the median OS was 7.1 months (95% CI 6.1–8.4). The overall drug-related death rate (drug-related grade 5 AEs rate) was 0.8% (95% CI 0.3–1.4), and the average drug-related grade 3/4 AE rate per person was 0.45 (95% CI 0.40–0.50). Conclusions Our findings suggest that, on average, one in five cancer patients in umbrella trials published between 1 January 2006 and 7 October 2019 responded to a given therapy, while one in 125 died due to drug toxicity. Our findings do not support the expectation of increased patient benefit in cancer umbrella trials. Further studies should investigate whether umbrella trial design and the precision oncology approach improve patient outcomes. |
| first_indexed | 2024-04-13T14:00:31Z |
| format | Article |
| id | doaj.art-fde121abb1274be4bdfa675f15665d8f |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-04-13T14:00:31Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj.art-fde121abb1274be4bdfa675f15665d8f2022-12-22T02:44:04ZengBMCBMC Medicine1741-70152022-07-0120111610.1186/s12916-022-02420-2Risk and benefit for umbrella trials in oncology: a systematic review and meta-analysisKarolina Strzebonska0Mateusz Blukacz1Mateusz T. Wasylewski2Maciej Polak3Bishal Gyawali4Marcin Waligora5Research Ethics in Medicine Study Group (REMEDY), Faculty of Health Sciences, Jagiellonian University Medical CollegeInstitute of Psychology, University of SilesiaResearch Ethics in Medicine Study Group (REMEDY), Faculty of Health Sciences, Jagiellonian University Medical CollegeResearch Ethics in Medicine Study Group (REMEDY), Faculty of Health Sciences, Jagiellonian University Medical CollegeDepartment of Oncology and the Department of Public Health Sciences, Queen’s UniversityResearch Ethics in Medicine Study Group (REMEDY), Faculty of Health Sciences, Jagiellonian University Medical CollegeAbstract Background Umbrella clinical trials in precision oncology are designed to tailor therapies to the specific genetic changes within a tumor. Little is known about the risk/benefit ratio for umbrella clinical trials. The aim of our systematic review with meta-analysis was to evaluate the efficacy and safety profiles in cancer umbrella trials testing targeted drugs or a combination of targeted therapy with chemotherapy. Methods Our study was prospectively registered in PROSPERO (CRD42020171494). We searched Embase and PubMed for cancer umbrella trials testing targeted agents or a combination of targeted therapies with chemotherapy. We included solid tumor studies published between 1 January 2006 and 7 October 2019. We measured the risk using drug-related grade 3 or higher adverse events (AEs), and the benefit by objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). When possible, data were meta-analyzed. Results Of the 6207 records identified, we included 31 sub-trials or arms of nine umbrella trials (N = 1637). The pooled overall ORR was 17.7% (95% confidence interval [CI] 9.5–25.9). The ORR for targeted therapies in the experimental arms was significantly lower than the ORR for a combination of targeted therapy drugs with chemotherapy: 13.3% vs 39.0%; p = 0.005. The median PFS was 2.4 months (95% CI 1.9–2.9), and the median OS was 7.1 months (95% CI 6.1–8.4). The overall drug-related death rate (drug-related grade 5 AEs rate) was 0.8% (95% CI 0.3–1.4), and the average drug-related grade 3/4 AE rate per person was 0.45 (95% CI 0.40–0.50). Conclusions Our findings suggest that, on average, one in five cancer patients in umbrella trials published between 1 January 2006 and 7 October 2019 responded to a given therapy, while one in 125 died due to drug toxicity. Our findings do not support the expectation of increased patient benefit in cancer umbrella trials. Further studies should investigate whether umbrella trial design and the precision oncology approach improve patient outcomes.https://doi.org/10.1186/s12916-022-02420-2Umbrella trialRisk-benefit balanceEthicsTargeted therapy |
| spellingShingle | Karolina Strzebonska Mateusz Blukacz Mateusz T. Wasylewski Maciej Polak Bishal Gyawali Marcin Waligora Risk and benefit for umbrella trials in oncology: a systematic review and meta-analysis BMC Medicine Umbrella trial Risk-benefit balance Ethics Targeted therapy |
| title | Risk and benefit for umbrella trials in oncology: a systematic review and meta-analysis |
| title_full | Risk and benefit for umbrella trials in oncology: a systematic review and meta-analysis |
| title_fullStr | Risk and benefit for umbrella trials in oncology: a systematic review and meta-analysis |
| title_full_unstemmed | Risk and benefit for umbrella trials in oncology: a systematic review and meta-analysis |
| title_short | Risk and benefit for umbrella trials in oncology: a systematic review and meta-analysis |
| title_sort | risk and benefit for umbrella trials in oncology a systematic review and meta analysis |
| topic | Umbrella trial Risk-benefit balance Ethics Targeted therapy |
| url | https://doi.org/10.1186/s12916-022-02420-2 |
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