Evidence map›Paper›PMID 33360855›Full record

ArticleEuropean journal of cancer (Oxford, England : 1990)2021

Long-term safety of pembrolizumab monotherapy and relationship with clinical outcome: A landmark analysis in patients with advanced melanoma.

Caroline Robert, Wen-Jen Hwu, Omid Hamid, Antoni Ribas, Jeffrey S Weber, Adil I Daud, F Stephen Hodi, Jedd D Wolchok, Tara C Mitchell, Peter Hersey and 13 more

3 registry-linked trialsOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of cancer (Oxford, England : 1990), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 65 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 6 pooled it
4.4field-weighted citation impact, top 4% 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.

NCT01295827 phase1completednot on this map

Phase I Study of Single Agent Pembrolizumab (MK-3475) in Patients With Progressive Locally Advanced or Metastatic Carcinoma, Melanoma, and Non-Small Cell Lung Carcinoma (KEYNOTE 001)

TypeinterventionalSponsorMerck Sharp & Dohme LLCRan2011 to 2018Enrolled1,260ConditionsCancer, Solid TumorArmsPembrolizumab
NCT01704287 phase2completednot on this map

Randomized, Phase II Study of Pembrolizumab (MK-3475) Versus Chemotherapy in Patients With Advanced Melanoma (KEYNOTE 002)

TypeinterventionalSponsorMerck Sharp & Dohme LLCRan2012 to 2019Enrolled540ConditionsMalignant MelanomaArmsPembrolizumab, Carboplatin, Paclitaxel, Dacarbazine, Temozolomide
NCT01866319 phase3completednot on this map

A Multicenter, Randomized, Controlled, Three-Arm, Phase III Study to Evaluate the Safety and Efficacy of Two Dosing Schedules of Pembrolizumab (MK-3475) Compared to Ipilimumab in Patients With Advanced Melanoma

TypeinterventionalSponsorMerck Sharp & Dohme LLCRan2013 to 2019Enrolled834ConditionsMelanomaArmsPembrolizumab, Ipilimumab
3 · Its place in the literature

Who cites it

65 citing papers in PubMed, 6 syntheses or guidelines pooled it, 96 citations in OpenAlex.

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5 more citing papers are in PubMed but not listed here.

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

23 authors at 18 institutions in 6 countries.

Caroline RobertDepartment of Oncology, Service of Dermatology, Institut de Cancérologie Gustave Roussy, 114 Rue Edouard Vaillant, Gustave Roussy, Villejuif, 94805, France; Paris-Saclay University, CNRS UMR 3348, Orsay, France. Electronic address: caroline.robert@gustaveroussy.fr.
Wen-Jen HwuDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. Electronic address: hwu.wenjen@gmail.com.
Omid HamidDepartment of Hematology/Oncology, The Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, 11800 Wilshire Blvd Suite 300, Los Angeles, CA, 90025, USA. Electronic address: ohamid@theangelesclinic.org.
Antoni RibasDepartment of Medicine and the Jonsson Comprehensive Cancer Center, University of California, Los Angeles (UCLA), 11-934 Factor bldg., Los Angeles, CA, 90095, USA. Electronic address: aribas@mednet.ucla.edu.
Jeffrey S WeberDepartment of Medicine, Laura and Isaac Perlmutter Cancer Center at NYU Langone Health, 522 First Avenue, 1310 Smilow Building, New York, NY, 10016, USA. Electronic address: Jeffrey.Weber@nyulangone.org.
Adil I DaudDepartment of Medicine, University of California San Francisco, 1600 Divisadero St, San Francisco, CA, 94158, USA. Electronic address: adaud@medicine.ucsf.edu.
F Stephen HodiMelanoma Center and Center for Immuno-Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA. Electronic address: Stephen_Hodi@dfci.harvard.edu.
Jedd D WolchokDepartment of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA. Electronic address: wolchokj@mskcc.org.
Tara C MitchellDivision of Hematology and Oncology, Abramson Cancer Center, University of Pennsylvania, 3400 Civic Center Blvd South Pavilion, Flr 10, Philadelphia, PA, 19104, USA. Electronic address: tara.mitchell@uphs.upenn.edu.
Peter HerseyDepartment of Medicine, The University of Sydney, Camperdown, NSW, 2006, Australia; Centenary Institute, Misendon Rd, Bldg 93, Camperdown, NSW, 2050, Australia; Melanoma Institute Australia, The University of Sydney, 40 Rocklands Rd, Wollstonecraft, NSW, 2065, Australia. Electronic address: peter.hersey@sydney.edu.au.
Roxana DroncaDepartment of Hematology/Oncology, Mayo Clinic, 200 1st St. SW, Rochester, MN, 55905, USA. Electronic address: Dronca.Roxana@mayo.edu.
Richard W JosephDivision of Cancer Medicine, Mayo Clinic Cancer Center-Florida, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA. Electronic address: joseph.richard@mayo.edu.
Celine BoutrosDepartment of Oncology, Service of Dermatology, Institut de Cancérologie Gustave Roussy, 114 Rue Edouard Vaillant, Gustave Roussy, Villejuif, 94805, France. Electronic address: celine.boutros@gustaveroussy.fr.
Le MinDivision of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA, 02115, USA. Electronic address: lmin@bwh.harvard.edu.
Georgina V LongMelanoma Institute Australia, The University of Sydney, 40 Rocklands Rd, Wollstonecraft, NSW, 2065, Australia; Royal North Shore Hospital, Reserve Road, St Leonards, NSW, 2065, Australia; Mater Hospital, Wollstonecraft, NSW, 2065, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, 2006, Australia. Electronic address: Georgina.Long@melanoma.org.au.
Jacob SchachterDivision of Oncology, Level 2 Cancer Center, Sheba Medical Center, Tel HaShomer Hospital, Emek HaEla Street 1, Tel HaShomer, Ramat Gan, 52621, Israel. Electronic address: jacob.schachter@sheba.health.gov.il.
Igor PuzanovMelanoma Section Department of Medicine, Roswell Park Comprehensive Cancer Center, 915 CSC Building, Elm & Carlton Streets, Buffalo, NY, 14263, USA. Electronic address: Igor.Puzanov@RoswellPark.org.
Reinhard DummerDepartment of Dermatology, University Hospital Zürich, University of Zurich, Rämistrasse 100, Zürich, 8091, Switzerland. Electronic address: reinhard.Dummer@usz.ch.
Jianxin LinDepartment of Clinical Oncology, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. Electronic address: jianxin_lin@merck.com.
Nageatte IbrahimDepartment of Clinical Oncology, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. Electronic address: nageatte.ibrahim@merck.com.
Scott J DiedeDepartment of Clinical Oncology, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. Electronic address: scott.diede@merck.com.
Matteo S CarlinoDepartment of Medicine, The University of Sydney, Camperdown, NSW, 2006, Australia; Melanoma Institute Australia, The University of Sydney, 40 Rocklands Rd, Wollstonecraft, NSW, 2065, Australia; Department of Medical Oncology, The Crown Princess Mary Cancer Centre, Westmead Hospital, 12 Moris Road, Westmead, NSW, 2145, Australia; Blacktown Hospital, 18 Blacktown Road, Blacktown, NSW, 2148, Australia. Electronic address: matteo.carlino@sydney.edu.au.
Anthony M JoshuaMelanoma Institute Australia, The University of Sydney, 40 Rocklands Rd, Wollstonecraft, NSW, 2065, Australia; Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, 610 University Ave, Toronto, ON, M5G2C1, Canada; The Kinghorn Cancer Centre at St Vincent's Hospital, 370 Victoria St, Darlinghurst, NSW, 2010, Australia; St Vincent's Clinical School, UNSW Sydney, Victoria St, Darlinghurst, NSW, 2010, Australia. Electronic address: Anthony.joshua@svha.org.au.
The University of Sydney · AUMerck & Co., Inc., Rahway, NJ, USA (United States) · USAngeles Clinic and Research Institute · USBrigham and Women's Hospital · USCentre National de la Recherche Scientifique · FRDana-Farber Cancer Institute · USInstitut Gustave Roussy · FRMayo Clinic · USMayo Clinic in Florida · USMemorial Sloan Kettering Cancer Center · USNYU Langone Health · USRoswell Park Comprehensive Cancer Center · USSheba Medical Center · ILThe University of Texas MD Anderson Cancer Center · USUniversity of California, Los Angeles · USUniversity of California, San Francisco · USUniversity of Pennsylvania · USUniversity of Zurich · CH

Funding

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

Abstract

objectiveLong-term safety of pembrolizumab in melanoma was analyzed in KEYNOTE-001, KEYNOTE-002, and KEYNOTE-006. PATIENTS AND

methodsAnalysis involved patients who received ≥1 pembrolizumab dose. Lead-time bias was addressed via landmark analyses in patients who were progression-free before day 147.

resultsAdverse events (AEs) were analyzed for 1567 patients (median follow-up, 42.4 months). Most AEs were mild/moderate; grade 3/4 treatment-related AEs occurred in 17.7% of patients. Two pembrolizumab-related deaths occurred. Any-grade immune-mediated AEs (imAEs) occurred in 23.0%, most commonly hypothyroidism (9.1%), pneumonitis (3.3%), and hyperthyroidism (3.0%); grade 3/4 imAEs occurred in 6.9% of patients. Most imAEs occurred within 16 weeks of treatment. In landmark analysis, patients who did (n = 79) versus did not (n = 384) develop imAEs had similar objective response rates (ORRs) (64.6% versus 63.0%); median time to response (TTR), 5.6 months for both; median duration of response (DOR), 20.0 versus 25.3 months; median progression-free survival (PFS), 17.0 versus 17.7 months; median overall survival (OS), not reached (NR) versus 43 months (p = 0.1104). Patients who did (n = 17) versus did not (n = 62) receive systemic corticosteroids had similar ORRs (70.6% vs. 62.9%) and median TTR (6.4 vs. 5.6 months) but numerically shorter median PFS (9.9 vs. 17.0 months); median DOR, 14.2 months versus NR; median OS, NR for both.

conclusionsThese results enhance the knowledge base for pembrolizumab in advanced melanoma, with no new toxicity signals after lengthy follow-up of a large population. In landmark analyses, pembrolizumab efficacy was similar regardless of imAEs or systemic corticosteroid use. CLINICAL TRIAL REGISTRY: NCT01295827, NCT01704287, NCT01866319.

Indexed as

AdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalClinical Trials as TopicDrug-Related Side Effects and Adverse ReactionsFemaleFollow-Up StudiesHumansMaleMelanomaMeta-Analysis as TopicMiddle AgedPrognosisYoung AdultAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalpembrolizumabAdvanced melanomaCorticosteroid useImmune-checkpoint inhibitorsImmune-related adverse eventsImmunomodulating drugsPD-1 inhibitorsPembrolizumab

Identifiers

PMID33360855
PMCPMC8388128
OpenAlexW3114638465

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.