PMID- 31145233
OWN - NLM
STAT- MEDLINE
DCOM- 20200618
LR  - 20200618
IS  - 1537-4513 (Electronic)
IS  - 1524-9557 (Linking)
VI  - 42
IP  - 6
DP  - 2019 Jul/Aug
TI  - Association Between Pembrolizumab-related Adverse Events and Treatment Outcome in 
      Advanced Melanoma: Results From the Dutch Expanded Access Program.
PG  - 208-214
LID - 10.1097/CJI.0000000000000271 [doi]
AB  - Toxicity of immune checkpoint inhibitors such as ipilimumab and nivolumab is 
      likely associated with clinical efficacy. In this study, we aim to evaluate this 
      association for pembrolizumab. To this end, data of 147 patients included in the 
      Dutch cohort of the Pembrolizumab Expanded Access Program were collected. All 
      data were collected prospectively. Patients with adverse events (AEs) at any time 
      during therapy showed a higher chance of achieving disease control compared with 
      patients without AEs (low-grade AEs vs. no AEs: odds ratio=12.8, P=0.0002, 
      high-grade AEs vs. no AEs: odds ratio=38.5, P=0.0001) according to a multivariate 
      logistic regression analysis. In addition, Cox regression analysis showed a lower 
      risk of death (hazard ratio: 0.51, 95% confidence interval: 0.28-0.97) and 
      disease progression (hazard ratio: 0.54, 95% confidence interval: 0.30-0.98) over 
      time for patients with high-grade AEs at any time during therapy compared with 
      patients without AEs during therapy. To correct for time dependency of occurrence 
      of AEs, a pseudolandmark analysis at 6 months of therapy was performed. Although 
      significance was lost (Wald test P>0.05), prolonged survival in 3 patients who 
      stopped therapy within 6 months due to the occurrence of AEs was observed, 
      suggesting the potential treatment benefit despite the premature ending of 
      therapy. The occurrence of high-grade toxicity at any time during treatment was 
      associated with higher objective response rates, progression-free survival, and 
      overall survival. There remains a need to assess the predictive value of early 
      occurring AEs on patient survival.
FAU - Bisschop, Cornelis
AU  - Bisschop C
AD  - Department of Medical Oncology, University Medical Center Groningen, Groningen.
FAU - Wind, Thijs T
AU  - Wind TT
AD  - Department of Medical Oncology, University Medical Center Groningen, Groningen.
FAU - Blank, Christian U
AU  - Blank CU
AD  - Department of Medical Oncology, Netherlands Cancer Institute NKI-AVL.
FAU - Koornstra, Rutger H T
AU  - Koornstra RHT
AD  - Department of Medical Oncology, Radboud University Medical Center, Nijmegen.
FAU - Kapiteijn, Ellen
AU  - Kapiteijn E
AD  - Department of Medical Oncology, Leiden University Medical Center, Leiden.
FAU - Van den Eertwegh, Alfonsus J M
AU  - Van den Eertwegh AJM
AD  - Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije 
      Universiteit Amsterdam, Amsterdam.
FAU - De Groot, Jan Willem B
AU  - De Groot JWB
AD  - Oncology Center Isala, Zwolle, The Netherlands.
FAU - Jalving, Mathilde
AU  - Jalving M
AD  - Department of Medical Oncology, University Medical Center Groningen, Groningen.
FAU - Hospers, Geke A P
AU  - Hospers GAP
AD  - Department of Medical Oncology, University Medical Center Groningen, Groningen.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized/*adverse effects/therapeutic use
MH  - Antineoplastic Agents, Immunological/*adverse effects/therapeutic use
MH  - Clinical Trials as Topic
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Male
MH  - Melanoma/*drug therapy/etiology/mortality/pathology
MH  - Neoplasm Staging
MH  - Netherlands
MH  - Proportional Hazards Models
MH  - Treatment Outcome
EDAT- 2019/05/31 06:00
MHDA- 2020/06/19 06:00
CRDT- 2019/05/31 06:00
PHST- 2019/05/31 06:00 [pubmed]
PHST- 2020/06/19 06:00 [medline]
PHST- 2019/05/31 06:00 [entrez]
AID - 10.1097/CJI.0000000000000271 [doi]
PST - ppublish
SO  - J Immunother. 2019 Jul/Aug;42(6):208-214. doi: 10.1097/CJI.0000000000000271.