PMID- 37230055
OWN - NLM
STAT- MEDLINE
DCOM- 20230630
LR  - 20230630
IS  - 1532-1967 (Electronic)
IS  - 0305-7372 (Linking)
VI  - 118
DP  - 2023 Jul
TI  - TROP-2 directed antibody-drug conjugates (ADCs): The revolution of smart drug 
      delivery in advanced non-small cell lung cancer (NSCLC).
PG  - 102572
LID - S0305-7372(23)00064-6 [pii]
LID - 10.1016/j.ctrv.2023.102572 [doi]
AB  - BACKGROUND: Antibody drug conjugates (ADCs) represent a revolutionary drug class 
      in cancer therapy, combining the precision of targeted therapy with the cytotoxic 
      effects of chemotherapy. Promising activity of novel ADCs, namely Trastuzumab 
      Deruxtecan and Patritumab Deruxtecan, has been observed in hard-to treat 
      molecular subtypes, such as HER2-positive and heavily pretreated EGFR-mutant 
      Non-Small Cell Lung Cancer (NSCLC). However, therapeutic advances are expected in 
      certain subgroups of lung cancer patients, including non-oncogene-addicted NSCLC 
      after failure of current standard of care (e.g., immunotherapy with or without 
      chemotherapy, chemo-antiangiogenic treatment). Trophoblastic Cell Surface Antigen 
      2 (TROP-2) is a surface transmembrane glycoprotein member of the epithelial cell 
      adhesion molecule (EpCAM) family. TROP-2 represents a promising therapeutic 
      target in refractory non-oncogene-addicted NSCLC. METHODOLOGY: We performed a 
      systematic literature search of the clinical trials about TROP-2 directed ADCs in 
      NSCLC referenced in the pubmed.gov database, Cochrane Library database and 
      clinicaltrial.gov database. RESULTS: First-in-humans ADCs targeting TROP-2, 
      namely Sacituzumab Govitecan (SN-38) and Datopotamab Deruxtecan (Dxd), yielded 
      promising activity signals in NSCLC with a manageable safety profile. Most common 
      grade >/= 3 adverse events (AEs) of Sacituzumab Govitecan included neutropenia 
      (28 %), diarrhea (7 %), nausea (7 %), fatigue (6 %), and febrile neutropenia 
      (4 %). Nausea and stomatitis were the most common all grade AEs with Datopotamab 
      Deruxtecan; dyspnea, amylase increase, hyperglycemia and lymphopenia were 
      reported as grade >/= 3 AEs in less than 12 % of patients. CONCLUSION: As more 
      effective strategies are needed for patients with refractory 
      non-oncogene-addicted NSCLC, the design of novel clinical trials with ADCs 
      targeting TROP-2 is encouraged as both a monotherapy or combination strategy with 
      existing agents (e.g., monoclonal antibodies targeting immune checkpoint 
      inhibitors or chemotherapy).
CI  - Copyright (c) 2023 Elsevier Ltd. All rights reserved.
FAU - Parisi, Claudia
AU  - Parisi C
AD  - Drug Development Department, International Center for Thoracic Cancers (CICT), 
      Gustave Roussy, Villejuif, France. Electronic address: 
      Claudia.PARISI@gustaveroussy.fr.
FAU - Mahjoubi, Linda
AU  - Mahjoubi L
AD  - Drug Development Department, International Center for Thoracic Cancers (CICT), 
      Gustave Roussy, Villejuif, France.
FAU - Gazzah, Anas
AU  - Gazzah A
AD  - Drug Development Department, International Center for Thoracic Cancers (CICT), 
      Gustave Roussy, Villejuif, France.
FAU - Barlesi, Fabrice
AU  - Barlesi F
AD  - Department of Medical Oncology, International Center for Thoracic Cancers (CICT), 
      Gustave Roussy, Villejuif, France; Universite Paris Saclay. Faculte de Medecine. 
      Kremlin-Bicetre, France.
LA  - eng
PT  - Journal Article
PT  - Review
PT  - Systematic Review
DEP - 20230519
PL  - Netherlands
TA  - Cancer Treat Rev
JT  - Cancer treatment reviews
JID - 7502030
RN  - 0 (Antineoplastic Agents)
RN  - XT3Z54Z28A (Camptothecin)
RN  - 0 (Immunoconjugates)
RN  - 7673326042 (Irinotecan)
SB  - IM
MH  - Humans
MH  - *Antineoplastic Agents/administration & dosage/adverse effects/therapeutic use
MH  - Camptothecin
MH  - *Carcinoma, Non-Small-Cell Lung/drug therapy
MH  - *Immunoconjugates/adverse effects/therapeutic use
MH  - Irinotecan
MH  - *Lung Neoplasms/drug therapy
OTO - NOTNLM
OT  - Antibody drug conjugates
OT  - Lung
OT  - NSCLC
OT  - Precision therapy
OT  - TROP-2
OT  - phase I
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/05/26 01:05
MHDA- 2023/06/26 06:41
CRDT- 2023/05/25 18:10
PHST- 2023/03/19 00:00 [received]
PHST- 2023/05/03 00:00 [revised]
PHST- 2023/05/11 00:00 [accepted]
PHST- 2023/06/26 06:41 [medline]
PHST- 2023/05/26 01:05 [pubmed]
PHST- 2023/05/25 18:10 [entrez]
AID - S0305-7372(23)00064-6 [pii]
AID - 10.1016/j.ctrv.2023.102572 [doi]
PST - ppublish
SO  - Cancer Treat Rev. 2023 Jul;118:102572. doi: 10.1016/j.ctrv.2023.102572. Epub 2023 
      May 19.