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Influence of companion diagnostics on efficacy and safety of targeted anti-cancer drugs: systematic review and meta-analyses.

ABSTRACT: Companion diagnostics aim to identify patients that will respond to targeted therapies, therefore increasing the clinical efficacy of such drugs. Less is known about their influence on safety and tolerability of targeted anti-cancer agents.Randomized trials evaluating targeted agents for solid tumors approved by the US Food and Drug Administration since year 2000 were assessed. Odds ratios (OR) and and 95% confidence intervals (CI) were computed for treatment-related death, treatment-discontinuation related to toxicity and occurrence of any grade 3/4 adverse events (AEs). The 12 most commonly reported individual AEs were also explored. ORs were pooled in a meta-analysis. Analysis comprised 41 trials evaluating 28 targeted agents. Seventeen trials (41%) utilized companion diagnostics. Compared to control groups, targeted drugs in experimental arms were associated with increased odds of treatment discontinuation, grade 3/4 AEs, and toxic death irrespective of whether they utilized companion diagnostics or not. Compared to drugs without available companion diagnostics, agents with companion diagnostics had a lower magnitude of increased odds of treatment discontinuation (OR = 1.12 vs. 1.65, p < 0.001) and grade 3/4 AEs (OR = 1.09 vs. 2.10, p < 0.001), but no difference in risk of toxic death (OR = 1.40 vs. 1.27, p = 0.69). Differences between agents with and without companion diagnostics were greatest for diarrhea (OR = 1.29 vs. 2.43, p < 0.001), vomiting (OR = 0.86 vs. 1.44, p = 0.005), cutaneous toxicity (OR = 1.82 vs. 3.88, p < 0.001) and neuropathy (OR = 0.64 vs. 1.60, p < 0.001).Targeted drugs with companion diagnostics are associated with improved safety, and tolerability. Differences were most marked for gastrointestinal, cutaneous and neurological toxicity.

SUBMITTER: Ocana A

PROVIDER: S-EPMC4741844 | biostudies-other | 2015 Nov

REPOSITORIES: biostudies-other

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Influence of companion diagnostics on efficacy and safety of targeted anti-cancer drugs: systematic review and meta-analyses.

Ocana Alberto A Ethier Josee-Lyne JL Díez-González Laura L Corrales-Sánchez Verónica V Srikanthan Amirrtha A Gascón-Escribano María J MJ Templeton Arnoud J AJ Vera-Badillo Francisco F Seruga Bostjan B Niraula Saroj S Pandiella Atanasio A Amir Eitan E

Oncotarget 20151101 37

<h4>Background</h4>Companion diagnostics aim to identify patients that will respond to targeted therapies, therefore increasing the clinical efficacy of such drugs. Less is known about their influence on safety and tolerability of targeted anti-cancer agents.<h4>Methods and findings</h4>Randomized trials evaluating targeted agents for solid tumors approved by the US Food and Drug Administration since year 2000 were assessed. Odds ratios (OR) and and 95% confidence intervals (CI) were computed fo ...[more]

PMID: 26446908

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Project description:Objective Non-steroidal anti-inflammatory drugs are used as first-line treatment of primary dysmenorrhea, but there has been no optimal clinical choice among non-steroidal anti-inflammatory drugs yet. The present study was to assess the relative benefits of different common non-steroidal anti-inflammatory drugs for primary dysmenorrhea patients with a network meta-analysis. Methods Randomized controlled trials were screened by our criteria and included in the network meta-analysis. Pain relief was considered as primary outcomes and adverse effect was supplied as a safety outcome, while additional rescue, assessment score, and pain intensity difference were secondary outcomes. All the indexes were evaluated with odds ratio or standardized mean difference. Surface under cumulative ranking curve result was used to calculate the ranking of each treatment. Results Totally, 72 randomized controlled trials of 5723 patients and 13 drugs were included in our study after screening. As for pain relief, all drugs except nimesulide, rofecoxib, and waldecoxib were superior to aspirin (odds ratio with 95% credible intervals, diclofenac: 0.28 (0.08, 0.86), flurbiprofen: 0.10 (0.03, 0.29), ibuprofen: 0.32 (0.14, 0.73), indomethacin: 0.21 (0.07, 0.58), ketoprofen: 0.25 (0.10, 0.64), mefenamic acid: 0.28 (0.09, 0.87), naproxen: 0.31 (0.15, 0.64), piroxicam: 0.15 (0.03, 0.59), and tiaprofenic acid: 0.17 (0.04, 0.63)). Aspirin also required additional rescue when compared with the majority of other drugs (flurbiprofen: 3.46 (1.15, 11.25), ibuprofen: 6.30 (2.08, 20.09), mefenamic acid: 7.32 (1.51, 37.71), naproxen: 2.66 (1.17, 6.55), and tiaprofenic acid: 9.58 (1.43, 94.63)). As for assessment of the whole treatment, ketoprofen, naproxen, rofecoxib, and ibuprofen got higher score significantly than placebo. In addition, ibuprofen performed better than placebo in pain intensity difference. Considering the safety, tiaprofenic acid and mefenamic acid were noticeable in low risk, and indomethacin revealed higher risk than any other drugs. According to the results of network analysis and surface under cumulative ranking curve, flurbiprofen was considered to be the best one among all the treatments in efficacy, and aspirin was worse than most of others. On the other hand, tiaprofenic acid and mefenamic acid were indicated as the safest drugs. Conclusion Considering the efficacy and safety, we recommended flurbiprofen and tiaprofenic acid as the optimal treatments for primary dysmenorrhea.

Project description:Companion diagnostics are an indispensable part of personalized medicine and will likely continue to rapidly increase in number and application to disease areas. The first companion diagnostics were launched in the 1980s and in the face of significant initial skepticism from drug developers as to whether segmenting a drug's market through a diagnostic was advisable. The commercial success of drugs such as Herceptin® (trastuzumab) and Gleevec® (imatinib), which both require testing with companion diagnostics before they can be prescribed, has moved the entire companion diagnostic field forward. From an initial start of a handful of oncology drugs with corresponding diagnostics, the field has expanded to include multiple therapeutic areas, and the number of combinations has grown by 12-fold. Based on drugs in clinical trials, the rapid growth will likely continue for the foreseeable future. This expansion of companion diagnostics will also have a global component as markets in Europe will evolve in a similar but not identical pattern as the US. One of the greatest challenges to future growth in companion diagnostics is aligning the incentives of all stakeholders. A major driver of growth will continue to be the economic incentives for drug developers to pair their products with diagnostics. However, diagnostic companies are caught between the conflicting demands of two major stakeholders, pharmaceutical companies on one hand and payers/providers on the other. Regulators are also becoming more demanding in aligning development time lines between drugs and diagnostics. In order to survive and prosper, diagnostic companies will need to think more broadly about companion diagnostics than the historical match between a specific drug and a single diagnostic. They will also have to continue the process of consolidation and global expansion that the industry has already begun. Despite these potential obstacles, companion diagnostics have become one of the hottest areas of deal making in the diagnostic space in recent years, and the future trends continue to look bright.

Dataset Information

Influence of companion diagnostics on efficacy and safety of targeted anti-cancer drugs: systematic review and meta-analyses.

Publications

Influence of companion diagnostics on efficacy and safety of targeted anti-cancer drugs: systematic review and meta-analyses.

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