Evidence map›Paper›PMID 35618285›Full record

Trial reportJournal for immunotherapy of cancer2022

Efficacy of pembrolizumab in patients with advanced cancer of unknown primary (CUP): a phase 2 non-randomized clinical trial.

Kanwal P Raghav, Bettzy Stephen, Daniel D Karp, Sarina A Piha-Paul, David S Hong, Dipti Jain, Dilichukwu O Chudy Onwugaje, Abdulrahman Abonofal, Anneleis F Willett, Michael Overman and 5 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02721732 (Phase II Study for the Evaluation of Efficacy of Pembrolizumab), which is not on this map. Cited by 36 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 2 pooled it
4.0field-weighted citation impact, top 5% 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.

NCT02721732 phase2active not recruitingnot on this map

Phase II Study for the Evaluation of Efficacy of Pembrolizumab (MK-3475) in Patients With Rare Tumors

TypeinterventionalSponsorM.D. Anderson Cancer CenterRan2016 to 2028Enrolled157ConditionsAdvanced Malignant Solid Neoplasm, Carcinoma of Unknown Primary, Metastatic Adrenal Gland Pheochromocytoma, Metastatic Kidney Medullary CarcinomaArmsLaboratory Biomarker Analysis, Pembrolizumab, Questionnaire Administration
3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 40 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

15 authors at 1 institution in 1 country.

Kanwal P RaghavGastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA anaing@mdanderson.org KPRaghav@mdanderson.org.
Bettzy StephenInvestigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Daniel D KarpInvestigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Sarina A Piha-PaulInvestigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.ORCID 0000-0001-9455-1660
David S HongInvestigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.ORCID 0000-0001-8721-1609
Dipti JainInvestigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Dilichukwu O Chudy OnwugajeInvestigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Abdulrahman AbonofalInvestigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Anneleis F WillettGastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Michael OvermanGastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Brandon SmagloGastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Ryan W HueyGastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Funda Meric-BernstamInvestigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Gauri R VaradhacharyGastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Aung NaingInvestigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA anaing@mdanderson.org KPRaghav@mdanderson.org.ORCID 0000-0002-4803-8513
The University of Texas MD Anderson Cancer Center · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

backgroundCancer of unknown primary (CUP) is an aggressive rare malignancy with limited treatment options. Data regarding clinical activity of immune checkpoint inhibitors in CUP is lacking. Therefore, we evaluated the efficacy of pembrolizumab, a programmed cell death-1 inhibitor, in patients with CUP.

methodsThe study was designed as a phase 2 basket trial for independent rare tumor cohorts including CUP. Adult patients with CUP who had progressed on previous systemic therapy, performance status 0/1 and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST V.1.1) were eligible. Patients received pembrolizumab (200 mg) intravenously every 21 days. Twenty-nine patients were enrolled and treated between August 2016 and June 2020. The primary endpoint was non-progression rate (NPR) at 27 weeks (NPR-27) per immune-related RECIST. Key prespecified secondary endpoints were confirmed objective response rate (ORR), safety, duration of response (DoR), progression-free survival (PFS) and overall survival (OS). Pretreatment biopsies were examined for biomarkers of response (programmed cell death ligand-1 (PD-L1) expression and tumor infiltrating lymphocytes (TILs)).

resultsAmong 25 (of 29 enrolled) eligible and evaluable patients, 14 (56%) had poorly differentiated carcinoma. Patients received a median of two lines of therapy prior to enrollment. Median follow-up was 27.3 months. NPR-27 was observed in seven patients (28.0% (95% CI: 12.1 to 49.4)). ORR was 20.0% (95% CI: 6.8 to 40.7) with five patients achieving immune-related partial response with median DoR of 14.7 months (95% CI: 9.8 to 19.6). Median PFS and OS were 4.1 (95% CI: 3.1 to 5.1) and 11.3 (95% CI: 5.5 to 17.1) months, respectively. Treatment-related adverse events of any and grade ≥3 were seen in 19 (76%) and 4 (16%) patients, respectively. One (4%) patient had grade 3 immune-related acute kidney injury requiring treatment discontinuation. Neither PD-L1 nor TILs were associated with NPR-27. Both positive PD-L1 staining (44.4% vs 6.3%; p=0.040) and intense TIL infiltration (44.4% vs 6.3%; p=0.040) were associated with response.

conclusionPembrolizumab showed encouraging efficacy in patients with CUP with acceptable safety profile. TRIAL REGISTRATION NUMBER: NCT02721732.

Indexed as

B7-H1 AntigenNeoplasms, Unknown PrimaryAdultAntibodies, Monoclonal, HumanizedHumansProgression-Free SurvivalAntibodies, Monoclonal, HumanizedB7-H1 Antigenpembrolizumabimmunotherapytherapies, investigational

Identifiers

PMID35618285
PMCPMC9125753
OpenAlexW4281568334

What OpenQuestion holds

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Registered trials

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.