Evidence map›Paper›PMID 39966752›Full record

SynthesisBMC cancer2025

Optimal early endpoint for second-line or subsequent immune checkpoint inhibitors in previously treated advanced solid cancers: a systematic review.

Jingqiu Li, Xiaoding Zhou, Lei Wu, Jiabao Ma, Yan Tan, Songke Wu, Jie Zhu, Qifeng Wang, Qiuling Shi

Abstract readSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in BMC cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Jingqiu Li *Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China.
Xiaoding Zhou *Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China.
Lei WuDepartment of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China.
Jiabao MaDepartment of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China.
Yan TanDepartment of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China.
Songke WuDepartment of Oncology, People'S Hospital of Cangxi County, Guangyuan, China. 13688013882@163.com.
Jie ZhuDepartment of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China. zhujiescch@163.com.
Qifeng WangDepartment of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China. littlecancer@163.com.
Qiuling ShiCenter for Cancer Prevention Research, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China.

Funding

Science and Technology Department of Sichuan Province 2023YFQ0055
6 · The paper itself

Abstract

backgroundThe administration of second-line or subsequent immune checkpoint inhibitors (ICIs) in previously treated patients with advanced solid cancers has been clinically investigated. However, previous clinical trials lacked an appropriate primary endpoint for efficacy assessment. This systematic review aimed to explore the most optimal early efficacy endpoint for such trials.

methodsPhase 2 or 3 clinical trials involving patients with advanced solid cancers with disease progression following standard first-line therapy receiving second-line or subsequent ICI administration, with adequate survival outcome data, were included from PubMed, Embase, Web of Science, and Cochrane Library databases before February 2023. Quality assessment was conducted using the Cochrane tool and Newcastle-Ottawa Quality Assessment Scale for Cohort Studies for randomized controlled trials (RCTs) and non-randomized trials, respectively. Objective response rate (ORR) and progression-free survival (PFS) at 3, 6, and 9 months were investigated as potential early efficacy endpoint candidates for 12-month overall survival (OS), with a strong correlation defined as Pearson's correlation coefficient r ≥ 0.8.

resultsA total of 64 RCTs comprising 22,725 patients and 106 non-randomized prospective trials involving 10,608 participants were eligible for modeling and external validation, respectively. RCTs examined 15 different cancer types, predominantly non-small-cell lung cancer (NSCLC) (17, 28%), melanoma (9, 14%), and esophageal squamous cell carcinoma (5, 8%). The median sample size of RCTs was 124 patients, and the median follow-up time was 3.2-57.7 months. The ORR (r = 0.38; 95% confidence interval [CI], 0.18-0.54) and PFS (r = 0.42; 95% CI, 0.14-0.64) exhibited weak trial-level correlations with OS. Within ICI treatment arms, the r values of ORR and 3-, 6-, and 9-month PFS with 12-month OS were 0.61 (95% CI, 0.37-0.79), 0.78 (95% CI, 0.62-0.88), 0.84 (95% CI, 0.77-0.90), and 0.86 (95% CI, 0.79-0.90), respectively. External validation of 6-month PFS indicated an acceptable discrepancy between actual and predicted 12-month OS.

conclusionsIn non-randomized phase 2 trials on second-line or subsequent ICI therapy in patients with advanced solid cancers, 6-month PFS could serve as an early efficacy endpoint. However, early efficacy endpoints are not recommended in RCTs to replace OS.

Indexed as

Endpoint DeterminationImmune Checkpoint InhibitorsNeoplasmsClinical Trials, Phase II as TopicHumansProgression-Free SurvivalRandomized Controlled Trials as TopicTreatment OutcomeImmune Checkpoint InhibitorsAdvanced solid cancerEarly efficacy endpointImmune checkpoint inhibitorObjective responseOverall survivalProgression-free survival

Identifiers

PMID39966752
PMCPMC11837729

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.