Evidence map›Paper›PMID 32276948›Full record

ArticleESMO open2020

Infection risk with PI3K-AKT-mTOR pathway inhibitors and immune checkpoint inhibitors in patients with advanced solid tumours in phase I clinical trials.

Yutaka Fujiwara, Aya Kuchiba, Takafumi Koyama, Ryunosuke Machida, Akihiko Shimomura, Shigehisa Kitano, Toshio Shimizu, Noboru Yamamoto

Open access · goldAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in ESMO open, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.4field-weighted citation impact, top 37% 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

6 citing papers in PubMed, 11 citations in OpenAlex.

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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

8 authors at 3 institutions in 2 countries.

Yutaka FujiwaraDepartment of Experimental Therapeutics, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan yutakafu@ncc.go.jp.ORCID 0000-0001-6981-0800
Aya KuchibaBiostatistics Division, Centre for Research Administration and Support, National Cancer Center Japan, Chuo-ku, Tokyo, Japan.
Takafumi KoyamaDepartment of Experimental Therapeutics, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
Ryunosuke MachidaBiostatistics Division, Centre for Research Administration and Support, National Cancer Center Japan, Chuo-ku, Tokyo, Japan.
Akihiko ShimomuraDepartment of Experimental Therapeutics, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
Shigehisa KitanoDepartment of Experimental Therapeutics, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
Toshio ShimizuDepartment of Experimental Therapeutics, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
Noboru YamamotoDepartment of Experimental Therapeutics, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
National Cancer Center Hospital East · JPNational Cancer Centre Japan · JPNational Cancer Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPatients undergoing chemotherapy are known to be at risk for infection from myelosuppression by cytotoxic agents (CTAs) or immunosuppressive effects from mTOR inhibitors. The infection risk of newly developed anticancer agents has not been fully evaluated. It remains unknown how T-cell activation induced by immune checkpoint inhibitors (ICIs) relates to infection.

methodsWe retrospectively examined infection risk in patients with cancer treated with investigational agents in a phase I study. The investigational agents were classified into four groups: CTA, phosphatidylinositol 3 kinase/Akt/mammalian target of rapamycin inhibitor (PAM), molecular targeted agent (MTA) and ICI. All infection-related adverse events (AEs) during treatment were recorded. We compared the CTA, PAM and ICI with MTA, because MTA are already considered low risk and were used in the largest number of patients.

resultsA total of 641 patients were enrolled: 35 CTAs (5.5%), 61 PAMs (9.5%), 445 MTAs (69.4%) and 100 ICIs (15.6%). Among all patients, 132 (20.6%) experienced infection-related AEs and 46 (7.2%) developed 50 ≥grade 3 infection-related AEs. In any infection-related AEs, the ORs compared with MTAs were 2.19 (95% CI 1.03 to 4.66) for CTAs, 3.55 (95% CI 2.02 to 6.24) for PAMs and 1.05 (95% CI 0.60 to 1.85) for ICIs, respectively. In time to the first infection-related AE analysis, the risks for any infection-related AE from CTAs and PAMs were higher than those from MTAs (HR 1.84 (95% CI 0.82 to 4.11); p=0.05 and 3.96 (95% CI 2.18 to 7.22); p<0.001). The risk from ICIs was not significantly different from that of MTAs (HR 0.71 (95% CI 0.46 to 1.10); p=0.19).

conclusionOur results validate that PAMs and CTAs carry a higher infection risk in patients with advanced solid tumours compared with MTAs. We suggest that the infection risk of ICIs is a similar infection risk to MTAs.

Indexed as

AdolescentAdultAgedAged, 80 and overFemaleHumansImmune Checkpoint InhibitorsMaleMiddle AgedNeoplasmsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRetrospective StudiesYoung AdultImmune Checkpoint InhibitorsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktAKTimmune checkpoint inhibitorinfectionmTORPI3K

Identifiers

PMID32276948
PMCPMC7174012
OpenAlexW3015390034

What OpenQuestion holds

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LicenceCC BY-NC
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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.