Evidence map›Paper›PMID 28920006›Full record

ArticleOncoimmunology

Dosing immunotherapy combinations: Analysis of 3,526 patients for toxicity and response patterns.

Mina Nikanjam, Harsh Patel, Razelle Kurzrock

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 11% 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

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.

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  6. Cancer: slaying the nine-headed Hydra.Annals of oncology : official journal of the European Society for Medical Oncology · 2023
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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

3 authors at 2 institutions in 1 country.

Mina NikanjamDivision of Hematology-Oncology, University of California Los Angeles, Los Angeles, CA, USA.
Harsh PatelDavid Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Razelle KurzrockCenter for Personalized Cancer Therapy and Division of Hematology and Oncology, UC San Diego Moores Cancer Center, San Diego, CA, USA.
University of California, Los Angeles · USUniversity of California San Diego · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Training for Academic HematologyT32HL066992 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHUTE, JOHN P, TIMMERMAN, JOHN M · 2002 to 2017
$3.6M
NCI NIH HHS P30 CA016672NHLBI NIH HHS T32 HL066992
6 · The paper itself

Abstract

Immunotherapy combinations are used to improve outcomes in metastatic cancer, but evidence-based knowledge of appropriate starting doses for novel combinations is lacking. Phase I-III adult combination clinical trials (≥ 1 drug was immunotherapy; anti-PD-1, PD-L1, or CTLA-4) were reviewed (PubMed Jan 1, 2010 to Sep 1, 2016; ASCO 2014-2016, ASH/ESMO 2014-2015 abstracts). The safe dose for each drug used in each combination was divided by the single-agent recommended dose to calculate dose percentage. Additive dose percentage was the sum of each dose percentage. Overall, 84 studies (N = 3,526 patients, 59 combinations) were analyzed. In 50% of studies, all drugs could be administered at full dose; 63%, in the presence of anti-PD-1/PD-L1 and 36% with anti-CTLA-4. The lowest safe starting dose for a doublet combination including a second immunotherapy was 50% of each drug; 60%, for a targeted agent. Most doublet/triplets combining anti-PD-1/PD-L1 with cytotoxics were tolerable at full doses. Response rates (median [interquartile range]) were higher for 3-drug than 2-drug combinations (53% [33-63%] (N = 23 studies) vs. 23% [14-39%]) (N = 60 studies) (p < 0.0001) with similar rates seen for targeted, cytotoxic, biologic, or additional immunotherapy combinations (p = 0.35). In conclusion, anti-PD-1/PD-L1 checkpoint inhibitors can be safely given with a variety of other immunotherapy and targeted agents, albeit at about half dose. Doublet and triplet combinations with cytotoxics could mostly be given at full doses. Anti-CTLA-4 agents compromised dosing more than anti-PD-1/PD-L1 agents. Response rates were significantly higher for 3- versus 2-drug combinations.

Indexed as

Immunotherapymaximum tolerated doseprecision medicinerecommended phase 2 dosetargeted therapy

Identifiers

PMID28920006
PMCPMC5593707
OpenAlexW2733692754

What OpenQuestion holds

Textmetadata
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.