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

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 che-motherapeutic drug, however "drug" can also be associated with other cy-totoxic payloads such as radionuclides, termed more specifically, Anti-body 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 ra-dionuclide used (90 Y, 131 I or 177 Lu). 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 front-line 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.
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Jean-François Chatal, Françoise Kraeber-Bodéré, Caroline Bodet-Milin, Caroline Rousseau. Therapeutic Immunoconjugates. Which Cytotoxic Payload: Chemotherapeutic Drug (ADC) or Radionuclide (ARC) ?. Current Cancer Therapy Reviews, Bentham Science Publishers, 2016, 12 (1), pp.54-65. ⟨10.2174/1573394712666160805121⟩. ⟨inserm-02913636⟩



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