Evidence map›Paper›PMID 35183043›Full record

SynthesisESMO open2022

Correlation between treatment effects on response rate and progression-free survival and overall survival in trials of targeted therapies in molecularly enriched populations.

B J Solomon, H H Loong, Y Summers, Z M Thomas, P French, B K Lin, A Sashegyi, J Wolf, J C-H Yang, A Drilon

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in ESMO open, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 3 pooled it
2.6field-weighted citation impact, top 9% of its field
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

11 citing papers in PubMed, 3 syntheses or guidelines pooled it, 18 citations in OpenAlex.

  1. Pooled it
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  5. Review
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  11. Long non-coding RNAs involved in retinoblastoma.Journal of cancer research and clinical oncology · 2023
    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

10 authors at 7 institutions in 6 countries.

B J SolomonPeter MacCallum Cancer Centre, Melbourne, Australia. Electronic address: Ben.Solomon@petermac.org.
H H LoongDepartment of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR.
Y SummersThe Christie Hospital, Manchester, UK.
Z M ThomasEli Lilly and Company, Indianapolis, USA.
P FrenchEli Lilly and Company, Indianapolis, USA.
B K LinEli Lilly and Company, Indianapolis, USA.
A SashegyiEli Lilly and Company, Indianapolis, USA.
J WolfCentrum für Integrierte Onkologie (CIO), Universitätsklinikum Köln, Cologne, Germany.
J C-H YangDepartment of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
A DrilonMemorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, USA.
Eli Lilly (United States) · USCentrum für Integrierte Onkologie · DEChinese University of Hong Kong · CNMemorial Sloan Kettering Cancer Center · USNational Taiwan University Hospital · TWPeter MacCallum Cancer Centre · AUThe Christie Hospital · GB

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundThe number of randomized trials of agents targeting oncogene-addicted tumors has surged in the past 10 years. Using a meta-analysis, we explored whether improvements in objective response rate (ORR) in comparative trials using targeted agents could serve as a potential surrogate endpoint for improvements in progression-free survival (PFS) or overall survival (OS) in populations with oncogene-addicted cancer. PATIENTS AND

methodsUsing commercial text mining software I2E, we searched ClinicalTrials.gov and MEDLINE databases for randomized, phase III trials based on prospectively defined criteria, including (i) use of agents targeting EGFR activating mutations, ALK rearrangements, BRAF V600E or V600K mutations, and BCR-ABL fusion protein; (ii) molecularly enriched trial population or subpopulation; (iii) control arm only randomized to chemo/cytotoxic therapy. Correlative analyses were performed using ORR, OS, and PFS data from trials that met these criteria.

resultsA total of 62 trials were identified; 15 met all of the prespecified criteria. The ORR effect size (both the difference in ORR between arms and the log odds ratio) and log PFS hazard ratio were strongly correlated: -0.78 (P = 0.0007) for the ORR difference model; -0.74 (P = 0.0017) for the log odds ratio model. ORR effect size was positively correlated with the log OS hazard ratio, but more weakly: -0.67 (P = 0.013) for the ORR difference model and -0.58 (P = 0.036) for the log odds ratio model. Analysis of the treatment effects between OS and PFS found no correlation.

conclusionsThese analyses identified a strong correlation between treatment effects on ORR and PFS in randomized clinical trials investigating agents targeting oncogene-driven cancers. A weaker correlation was observed between ORR and OS. These meta-analysis results support the use of a high ORR forming the basis of an initial regulatory approval in biomarker-driven studies.

Indexed as

Antineoplastic AgentsNeoplasmsBiomarkersHumansOdds RatioProgression-Free SurvivalProportional Hazards ModelsRandomized Controlled Trials as TopicAntineoplastic AgentsBiomarkerscorrelationmeta-analysisobjective response rateoverall survivalprogression-free survivaltargeted therapy

Identifiers

PMID35183043
PMCPMC9058889
OpenAlexW4213305440

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.