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Neoadjuvant therapy versus upfront surgery in resectable pancreatic cancer according to intention-to-treat and per-protocol analysis: A systematic review and meta-analysis.

ABSTRACT: The effectiveness of neoadjuvant therapy (NAT) remains unclear in resectable pancreatic cancer (PC) as compared with upfront surgery (US). The aim of this study was to investigate the survival gain of NAT over US in resectable PC. PubMed and EMBASE were searched for studies comparing survival outcomes between NAT and US for resectable PC until June 2018. Overall survival (OS) was analyzed according to treatment strategy (NAT versus US) and analytic methods (intention-to-treat analysis (ITT) and per-protocol analysis (PP)). In 14 studies, 2,699 and 6,992 patients were treated with NAT and US, respectively. Although PP analysis showed the survival gain of NAT (HR 0.72, 95% CI 0.68-0.76), ITT analysis did not show the statistical significance (HR 0.96, 95% CI 0.82-1.12). However, NAT completed with subsequent surgery showed better survival over US completed with adjuvant therapy (HR 0.82, 95% CI 0.71-0.93). In conclusion, the supporting evidence for NAT in resectable PC was insufficient because the benefit was not demonstrated in ITT analysis. However, among the patients who completed both surgery and chemotherapy, NAT showed survival benefit over adjuvant therapy. Therefore, NAT could have a role of triaging the patients for surgery even in resectable PC.

SUBMITTER: Lee YS

PROVIDER: S-EPMC6821820 | biostudies-other | 2019 Oct

REPOSITORIES: biostudies-other

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Neoadjuvant therapy versus upfront surgery in resectable pancreatic cancer according to intention-to-treat and per-protocol analysis: A systematic review and meta-analysis.

Lee Yoon Suk YS Lee Jong-Chan JC Yang Se Yeol SY Kim Jaihwan J Hwang Jin-Hyeok JH

Scientific reports 20191030 1

The effectiveness of neoadjuvant therapy (NAT) remains unclear in resectable pancreatic cancer (PC) as compared with upfront surgery (US). The aim of this study was to investigate the survival gain of NAT over US in resectable PC. PubMed and EMBASE were searched for studies comparing survival outcomes between NAT and US for resectable PC until June 2018. Overall survival (OS) was analyzed according to treatment strategy (NAT versus US) and analytic methods (intention-to-treat analysis (ITT) and ...[more]

PMID: 31666626

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Project description:BackgroundIn non-inferiority trials, there is a concern that intention-to-treat (ITT) analysis, by including participants who did not receive the planned interventions, may bias towards making the treatment and control arms look similar and lead to mistaken claims of non-inferiority. In contrast, per protocol (PP) analysis is viewed as less likely to make this mistake and therefore preferable in non-inferiority trials. In a systematic review of antibiotic non-inferiority trials, we compared ITT and PP analyses to determine which analysis was more conservative.MethodsIn a secondary analysis of a systematic review, we included non-inferiority trials that compared different antibiotic regimens, used absolute risk reduction (ARR) as the main outcome and reported both ITT and PP analyses. All estimates and confidence intervals (CIs) were oriented so that a negative ARR favored the control arm, and a positive ARR favored the treatment arm. We compared ITT to PP analyses results. The more conservative analysis between ITT and PP analyses was defined as the one having a more negative lower CI limit.ResultsThe analysis included 164 comparisons from 154 studies. In terms of the ARR, ITT analysis yielded the more conservative point estimate and lower CI limit in 83 (50.6%) and 92 (56.1%) comparisons respectively. The lower CI limits in ITT analysis favored the control arm more than in PP analysis (median of - 7.5% vs. -6.9%, p = 0.0402). CIs were slightly wider in ITT analyses than in PP analyses (median of 13.3% vs. 12.4%, p < 0.0001). The median success rate was 89% (interquartile range IQR 82 to 93%) in the PP population and 44% (IQR 23 to 60%) in the patients who were included in the ITT population but excluded from the PP population (p < 0.0001).ConclusionsContrary to common belief, ITT analysis was more conservative than PP analysis in the majority of antibiotic non-inferiority trials. The lower treatment success rate in the ITT analysis led to a larger variance and wider CI, resulting in a more conservative lower CI limit. ITT analysis should be mandatory and considered as either the primary or co-primary analysis for non-inferiority trials.Trial registrationPROSPERO registration number CRD42020165040 .

Dataset Information

Neoadjuvant therapy versus upfront surgery in resectable pancreatic cancer according to intention-to-treat and per-protocol analysis: A systematic review and meta-analysis.

Publications

Neoadjuvant therapy versus upfront surgery in resectable pancreatic cancer according to intention-to-treat and per-protocol analysis: A systematic review and meta-analysis.

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