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Current Cancer Therapy Reviews

Editor-in-Chief

ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

Review Article

Therapeutic Immunoconjugates. Which Cytotoxic Payload: Chemotherapeutic Drug (ADC) or Radionuclide (ARC) ?

Author(s): Jean-François Chatal, Françoise Kraeber-Bodéré, Caroline Bodet-Milin and Caroline Rousseau

Volume 12 , Issue 1 , 2016

Page: [54 - 65] Pages: 12

DOI: 10.2174/1573394712666160805121312

Price: $65

Abstract

Over the last decade, Antibody Drug Conjugates (ADCs) have gained a great success due to their documented clinical efficacy and manageable toxicity. Generally the word “drug” is associated with a chemotherapeutic drug, however “drug” can also be associated with other cytotoxic payloads such as radionuclides, termed more specifically, Antibody Radionuclide Conjugates (ARCs) for radioimmunotherapy (RIT).

A large number of clinical studies have evaluated both ADCs and ARCs in varied indications. This review collected the clinical results of 11 studies including 598 patients treated with 6 ADCs and 9 studies including 377 patients treated with 5 ARCs. Toxicity was generally less frequent with ADCs than with ARCs but often led to more uncomfortable side effects. Hematological toxicity was higher with ARCs than with ADCs regardless of the radionuclide used (90Y, 131I or 177Lu).

For radiosensitive hematological malignancies overall response rates varied from 7 to 86% (median: 50%) with ADCs and from 31 to 95% (median: 83%) with ARCs. Two studies including 135 patients were performed with ARCs in the most favorable situation of frontline therapy which can favor global efficacy. Median progression free survival (PFS) varied between 5.6 and 13.3 months (median: 7.8) with ADCs and between 6 and 25.9 months (median: 9.4) with ARCs, once again focusing on the most favorable situation of ARCs in frontline therapy. For solid tumors overall response rates varied from 6 to 34.5% (median: 15%) with ADCs and from 8 to 15% (median: 7.5%) with ARCs.

Both ADCs and ARCs have shown clinical efficacy with acceptable and manageable toxicity.

Keywords: Antibody drug conjugates, antibody radionuclide conjugates, radionuclide therapy, therapeutic immunoconjugates.

Graphical Abstract

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