Evidence map›Paper›PMID 29045514›Full record

ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2017

Exploratory analysis of the association of depth of response and survival in patients with metastatic non-small-cell lung cancer treated with a targeted therapy or immunotherapy.

C E McCoach, G M Blumenthal, L Zhang, A Myers, S Tang, R Sridhara, P Keegan, R Pazdur, R C Doebele, D Kazandjian

Erratum issuedAbstract read
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In one paragraph

Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 50 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 2 pooled it
–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

50 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

C E McCoachDivision of Medical Oncology, University of Colorado, Aurora.
G M BlumenthalOffice of Hematology and Oncology Products CDER, US Food and Drug Administration, Silver Spring.
L ZhangOffice of Biostatistics, CDER, US Food and Drug Administration, Silver Spring.
A MyersOffice of Hematology and Oncology Products CDER, US Food and Drug Administration, Silver Spring.
S TangOffice of Biostatistics, CDER, US Food and Drug Administration, Silver Spring.
R SridharaOffice of Biostatistics, CDER, US Food and Drug Administration, Silver Spring.
P KeeganOffice of Hematology and Oncology Products CDER, US Food and Drug Administration, Silver Spring.
R PazdurOffice of Hematology and Oncology Products CDER, US Food and Drug Administration, Silver Spring.
R C DoebeleDivision of Medical Oncology, University of Colorado, Aurora.
D KazandjianOffice of Hematology and Oncology Products CDER, US Food and Drug Administration, Silver Spring.

Funding

Tissue Bank and Biomarkers CoreP50CA058187 · NCI · UNIVERSITY OF COLORADO DENVER · PI MILLER, YORK E · 1992 to 2018
$43.8M
NCI NIH HHS P50 CA058187
6 · The paper itself

Abstract

backgroundResponse Evaluation Criteria in Solid Tumors (RECIST) permits rapid evaluation of new therapeutic strategies in cancer. However, RECIST does not capture the heterogeneity of response in highly active therapies. Depth of tumor response may provide a more granular view of response. We explored the association between, depth of response (DepOR), with overall survival (OS) and progression-free survival (PFS) for patients with NSCLC being treated with an ALK inhibitor (ALKi) or an anti-PD-1 antibody (Ab).

methodsExperimental arms from two randomized controlled trials (RCTs) of an ALKi and two RCTs of an anti-PD-1 Ab were separately pooled. Patient responses were grouped into DepOR 'quartiles' by percentage of maximal tumor shrinkage (Q1 = 1%-25%, Q2 = 26%-50%, Q3 = 51%-75%, and Q4 = 76%-100%), Q0 had no shrinkage. We carried out a retrospective exploratory responder analysis to evaluate the association between DepOR and OS or PFS using hazard ratios (HR) generated by the Cox proportional hazards model.

resultsIn the pooled ALK analysis there were 12, 39, 70, 144, and 40 patients in quartiles 0-4, respectively. The DepOR versus PFS/OS analyses HR were: 0.19/0.94 for Q1 0.11/0.56 for Q2, 0.05/0.28 for Q3, and 0.03/0.05 for Q4. In the PD-1 trials within quartiles 0-4 there were 168, 70, 44, 45, and 28 patients, respectively. The DepOR versus PFS/OS analyses HR were 0.3/0.52 for Q1, 0.22/0.47 for Q2, 0.09/0.07 for Q3, and 0.07/0.14 for Q4.

conclusionsOur analysis suggests a greater DepOR is associated with longer PFS and OS for patients receiving ALKi or anti-PD1 Ab. Overall, this suggests that DepOR may provide an additional outcome measure for clinical trials, and may allow better comparisons of treatment activity.

Indexed as

ImmunotherapyMolecular Targeted TherapyAdultAgedAged, 80 and overAnaplastic Lymphoma KinaseAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungFemaleFollow-Up StudiesHumansLung NeoplasmsLymphatic MetastasisMaleMiddle AgedPrognosisALK protein, humanAnaplastic Lymphoma KinaseReceptor Protein-Tyrosine Kinasesdepth of responseimmune therapynon-small-cell lung cancerresponse criteriatargeted therapy

Identifiers

PMID29045514
PMCPMC6137816

What OpenQuestion holds

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Registered trials

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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.