TY  - CHAP
M1  - Book, Section
TI  - Melanoma
A1  - Safa, Houssein
A1  - Mattei, Jane
A1  - Bishop, Andrew J.
A1  - Keung, Emily Z.
A1  - Yadugiri, Sirisha
A1  - Davies, Michael A.
A1  - Oliva, Isabella C. Glitza
A2  - Kantarjian, Hagop M.
A2  - Wolff, Robert A.
A2  - Rieber, Alyssa G.
Y1  - 2022
N1  - 
T2  - The MD Anderson Manual of Medical Oncology, 4e
AB  - KEY  CONCEPTSMutations  in  the  RAS-RAF-MAPK  signaling  pathway  are  detected  in  most  cutaneous  melanomas,  most  commonly  affecting  BRAF,  NRAS,  and  Nf1.  The  prevalence  and  pattern  of  mutations  differs  between  cutaneous  melanomas  and  noncutaneous  (ie,  mucosal,  uveal)  melanomas.Surgery  is  the  mainstay  of  initial  treatment  for  patients  with  primary  cutaneous  melanoma  without  clinical  evidence  of  regional  nodal  or  distant  metastatic  disease.  Sentinel  lymph  node  biopsy  should  be  considered  in  patients  with  a  significant  risk  of  regional  metastasis.  For  patients  with  sentinel  lymph  node  involvement,  it  is  no  longer  standard  practice  to  perform  completion  lymph  node  dissection  based  on  recent  prospective  trials  that  showed  no  significant  impact  on  melanoma-specific  survival  (MSS).  Surgery  is  an  important  component  in  the  multidisciplinary  management  of  patients  with  clinically  detected  regional  nodal  disease  and  in  select  patients  with  distant  metastases.Adjuvant  radiation  therapy  (RT)  reduces  the  risk  of  locoregional  recurrence  in  patients  with  regionally  metastatic  disease  but  without  significant  impact  on  overall  survival  (OS).  Radiation  may  provide  palliative  benefit  in  patients  with  distant  metastases.  Treatment  decisions  regarding  radiation  should  be  tailored  based  on  potential  risks,  benefits,  and  multidisciplinary  input.Several  adjuvant  systemic  therapies  reduce  the  risk  of  recurrence  in  patients  with  regionally  metastatic  disease.  While  adjuvant  immune  checkpoint  inhibitor  immunotherapy  was  first  approved  for  the  anti–CTLA-4  (cytotoxic  Tlymphocyte-associated  antigen  4)  antibody  ipilimumab,  adjuvant  therapy  with  anti–PD-1  (programmed  cell  death  protein  1)  antibodies  (nivolumab,  pembrolizumab)  was  shown  to  be  safer  and  more  effective.  Adjuvant  targeted  therapy  with  the  combination  of  dabrafenib,  a  BRAF  inhibitor,  and  trametinib,  a  MEK  inhibitor,  is  approved  for  stage  III  melanomas  with  a  BRAF  V600  mutation.  No  prospective  trials  to  date  have  compared  adjuvant  immunotherapy  versus  adjuvant  targeted  therapy.  Both  immunotherapy  and  targeted  therapy  are  being  investigated  in  the  neoadjuvant  setting.After  decades  without  progress,  in  the  past  decade,  multiple  systemic  therapies  have  been  approved  for  the  treatment  for  patients  with  stage  IV  or  unresectable  stage  III  disease.  Ipilimumab  was  the  first  immunotherapy  to  be  approved  in  this  setting.  Subsequent  trials  demonstrated  improved  safety  and  efficacy  with  single-agent  nivolumab  and  with  single-agent  pembrolizumab  versus  ipilimumab,  leading  to  their  approval.  Combination  immunotherapy  with  ipilimumab  and  nivolumab  is  also  more  effective  than  ipilimumab  and  has  been  approved,  but  the  combination  has  increased  toxicity  versus  either  agent  alone.  For  patients  with  a  BRAF  V600  mutation,  three  different  targeted  therapy  combinations  of  a  BRAF  and  a  MEK  inhibitor  (dabrafenib  +  trametinib;  vemurafenib  +  cobimetinib;  encorafenib  +  binimetinib)  have  been  approved  after  demonstrating  superiority  compared  to  single-agent  BRAF  inhibitor  therapy.  The  BRAF  +  MEK  inhibitor  combinations  have  not  been  compared  in  prospective  clinical  trials  versus  each  other  or  versus  immunotherapy.  Intratumoral  injection  of  talimogene  laherparepvec  is  approved  for  patients  with  unresectable  injectable  metastatic  disease.Although  much  progress  has  been  made  for  patients  with  cutaneous  melanoma,  the  efficacy  of  immune  checkpoint  inhibitors  is  much  lower  in  patients  with  mucosal  and  with  uveal  melanoma.  These  tumor  types  also  have  a  much  lower  prevalence  of  targetable  mutations.  
SN  - 
PB  - McGraw Hill Education
CY  - New York, NY
Y2  - 2024/04/19
UR  - hemonc.mhmedical.com/content.aspx?aid=1190838322
ER  -