Off‐label and compassionate use of targeted anticancer therapies: The experience of an Italian pediatric cancer center

Abstract

Introduction:In Europe, despite recent advances in clinical development, most of the drugs currently used to treat childhood cancers are adult medicines, prescribed outside of the authorized indication. In this context, a monocentric retrospective cohort analysis was conducted, evaluating pediatric, adolescent, and young adult patients affected by onco-hematologic disease, treated with targeted therapies used off-label or as compassionate use. Methods:The analysis was conducted on 45 patients aged less than or equal to 30 years with cancer, having received at least one targeted therapy prescribed as offlabel or compassionate use at a large Italian pediatric center between January 1, 2016 and June 30, 2021. Data collected included information on the patient and tumor, data on off-label/compassionate treatment, and data on safety and efficacy.Results: Total 25 out of 45 patients treated with off-label or compassionate targeted therapies were affected by onco-hematological diseases. Overall, 22 out of the 52 agents (42%) were prescribed in patients with relapsed neoplasm and 39% (20/52) in patients with refractory diseases. Complete response was observed in more than half (27/52) of treatments. At least one adverse reaction occurred in 76% (n = 22) of agents administered to patients with onco-hematological tumor and in 43% (n = 10) of agents prescribed to patients with solid tumor. Conclusion:This work aims to provide a snapshot of off-label and compassionate use prescriptions in a large Italian pediatric cancer center. This study confirms that targeted agents for unauthorized indications are often prescribed in pediatric patients with cancer, especially after disease relapse and that these treatments are mostly tolerable and effective.

Safety of Off-Label Use of Anticancer Drugs in Oncology

“…Креативная хирургия и онкология / Creative Surgery and Oncology 2024;14(1):69-77 нения «вне инструкции» у пациентов со злокачественными новообразованиями (ЗНО) центральной нервной системы (ЦНС) [4]. R. Cenna и соавторы опубликовали результаты моноцентрового ретроспективного когортного анализа, в котором проводилось изучение клинических ситуаций c использованием терапии таргетными препаратами «вне инструкции» и по программам расширенного доступа у 45 пациентов со злокачественными новообразованиями в возрасте до 30 лет в крупном педиатрическом центре Италии [12]. Двадцать пять пациентов из 45 имели онкогематологические заболевания.…”

“…Как минимум одна побочная реакция отмечена при использовании 76 % препаратов (n = 22) у пациентов с онкогематологическими заболеваниями, и 43 % препаратов (n = 10), применявшихся у больных с солидными опухолями. Авторы исследования подтвердили частое использование таргетной терапии «вне инструкции» детям с онкологическими заболеваниями, особенно при рецидивах, отмечая при этом то, что данное лечение в большинстве случаев эффективно и переносимо [12]. A. Spini и соавторы, опубликовав результаты систематического обзора и метаанализа ряда клинических испытаний и обсервационных исследований, сообщили о том, что у каждого второго педиатрического пациента (≤18 лет) с солидной опухолью, для лечения которых применялись антиангиогенные препараты в качестве монотерапии, наблюдались серьезные нежелательные явления (НЯ) [7].…”

Off‐label prescribing of immune checkpoint inhibitor therapy at a single pediatric cancer center

“…8 In an Italian single-center study describing 45 patients treated with off-label or compassionate use of targeted anticancer therapies, the majority of use was in relapsed or refractory disease, 71% experienced at least one adverse drug reaction, and 52% achieved a complete response. 9 Over the last decade, immune checkpoint inhibition (ICI) has revolutionized the field of medical oncology, and the number of patients with adult malignancies treated with ICI has dramatically increased. 10,11 Retrospective studies and early phase clinical trials have demonstrated ICI to be safe and tolerable in pediatric patients with a variety of malignancies, [12][13][14][15][16][17][18][19][20][21][22][23] including central nervous system tumors.…”

“…One study evaluating the off‐label use of targeted therapy in pediatric cancers from 2007 to 2017 observed an overall prevalence of 9.2% 8 . In an Italian single‐center study describing 45 patients treated with off‐label or compassionate use of targeted anticancer therapies, the majority of use was in relapsed or refractory disease, 71% experienced at least one adverse drug reaction, and 52% achieved a complete response 9 …”

“… 8 In an Italian single‐center study describing 45 patients treated with off‐label or compassionate use of targeted anticancer therapies, the majority of use was in relapsed or refractory disease, 71% experienced at least one adverse drug reaction, and 52% achieved a complete response. 9 …”