Evidence map›Paper›PMID 26208946›Full record

ArticleTargeted oncology2016

Vemurafenib pharmacokinetics and its correlation with efficacy and safety in outpatients with advanced BRAF-mutated melanoma.

N Kramkimel, A Thomas-Schoemann, L Sakji, Jl Golmard, G Noe, E Regnier-Rosencher, N Chapuis, E Maubec, M Vidal, Mf Avril and 4 more

Abstract read
PubMed Publisher
In one paragraph

Article in Targeted oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

23 citing papers in PubMed, 50 citations in OpenAlex.

  1. Review
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  6. Review
  7. Article
  8. Article
  9. Precision Dosing of Targeted Therapies Is Ready for Prime Time.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
    Article
  10. Article
  11. Therapeutic drug monitoring of oral targeted antineoplastic drugs.European journal of clinical pharmacology · 2021
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Clinical Pharmacokinetics of Vemurafenib.Clinical pharmacokinetics · 2017
    Review
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

14 authors at 8 institutions in 1 country.

N KramkimelAssistance Publique Hôpitaux de Paris, Département de Dermatologie, Hôpital Cochin, Paris, France.
A Thomas-SchoemannCentre d'étude et de recours sur les inhibiteurs de l'angiogénèse (CERIA), Paris, France.
L SakjiCHRU de Lille, Service de Dermatologie, Paris, France.
Jl GolmardAssistance Publique Hôpitaux de Paris, Département de Biostatistiques, Hôpital Pitié-Salpêtrière, Paris, France.
G NoeAssistance Publique Hôpitaux de Paris, Unité Fonctionnelle de Pharmacocinétique et Pharmacochimie, Hôpital Cochin, 27 rue du Faubourg Saint Jacques, 75014, Paris, France.
E Regnier-RosencherAssistance Publique Hôpitaux de Paris, Département de Dermatologie, Hôpital Cochin, Paris, France.
N ChapuisAssistance Publique Hôpitaux de Paris, Service d'Hématologie biologique, Hôpital Cochin, Paris, France.
E MaubecAssistance Publique Hôpitaux de Paris, Département de Dermatologie, Hôpital Bichat, Paris, France.
M VidalCentre d'étude et de recours sur les inhibiteurs de l'angiogénèse (CERIA), Paris, France.
Mf AvrilAssistance Publique Hôpitaux de Paris, Département de Dermatologie, Hôpital Cochin, Paris, France.
F GoldwasserCentre d'étude et de recours sur les inhibiteurs de l'angiogénèse (CERIA), Paris, France.
L MortierCHRU de Lille, Service de Dermatologie, Paris, France.
N DupinAssistance Publique Hôpitaux de Paris, Département de Dermatologie, Hôpital Cochin, Paris, France.
B BlanchetCentre d'étude et de recours sur les inhibiteurs de l'angiogénèse (CERIA), Paris, France. benoit.blanchet@cch.aphp.fr.
Assistance Publique – Hôpitaux de Paris · FRHôpital Cochin · FRCentre Hospitalier Universitaire de Lille · FRDélégation Paris 5 · FRInserm · FRSorbonne Université · FRUniversité de Lille · FRUniversité Paris Cité · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Vemurafenib is a BRAF kinase inhibitor approved for first-line treatment of metastatic BRAF (V600) -mutant melanoma. However, data on the pharmacokinetic/pharmacodynamic (PK/PD) relationship are lacking. The aim of this prospective, multicenter study was to explore the PK/PD relationship for vemurafenib in outpatients with advanced BRAF-mutated melanoma. Fifty-nine patients treated with single-agent vemurafenib were prospectively analyzed. Vemurafenib plasma concentration (n = 159) was measured at days 15, 30, 60, and 90 after treatment initiation. Clinical and biological determinants (including plasma vemurafenib concentration) for efficacy and safety were assessed using Cox's model and multivariate stepwise logistic regression. Median progression-free survival (PFS) and overall survival were 5.0 (95 % confidence interval [95 % CI] 2.0-6.0) and 11.0 (95% CI 7.0-16.0) months, respectively. Twenty-nine patients (49 %) experienced any grade ≥3 toxicity and the most frequent grade ≥2 toxicity was skin rash (37 %). Severe toxicities led to definitive discontinuation in seven patients (12 %). Grade ≥2 skin rash was not statistically associated with better objective response at day 60 (p = 0.06) and longer PFS (hazard ratio 0.47; 95 % CI 0.21-1.08; p = 0.075). Grade ≥2 skin rash was statistically increased in patients with ECOG  ≥ 1 (odds ratio 4.67; 95 % CI 1.39-15.70; p = 0.012). Vemurafenib concentration below 40.4 mg/L at day 15 was significantly associated with a shorter PFS (1.5 [0.5-5.5] vs. 4.5 [2-undetermined] months, p = 0.029). Finally, vemurafenib concentration was significantly greater in patients developing grade ≥2 rash (61.7 ± 25.0 vs. 36.3 ± 17.9 mg/L, p < 0.0001). These results suggest that early plasma drug monitoring may help identify outpatients at high risk of non-response or grade ≥ 2 skin rash.

Indexed as

AgedBrain NeoplasmsFemaleFollow-Up StudiesHumansIndolesMaleMelanomaMiddle AgedMutationNeoplasm StagingPrognosisProspective StudiesProtein Kinase InhibitorsProto-Oncogene Proteins B-rafSulfonamidesBRAF protein, humanIndolesProtein Kinase InhibitorsProto-Oncogene Proteins B-rafSulfonamidesVemurafenib

Identifiers

PMID26208946
OpenAlexW952269252

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.