Off-Label Use of Immune Checkpoint Inhibitors: Is it Really Beneficial?

Published Nov 17, 2022

Anas Hamad, PhD, MSc1; Seif Abaza, PharmD1; Sahar Nasser, BScPharm1; Mohamed Abuyounis, BScPharm1; Amir Nounou, BScPharm1; Kakil Rasul, CABM, FRCP2; Shereen Elazzazy, PharmD, MBA1

(1) Pharmacy Department, National Center for Cancer Care & Research, Hamad Medical Corporation, Doha, Qatar

(2) Medical Oncology Department, National Center for Cancer Care & Research, Hamad Medical Corporation, Doha, Qatar

Immunotherapy has been a cornerstone of cancer treatment since it emerged in the late 2000s. Immune checkpoint inhibitors (ICIs) have played a significant role by covering tens of different indications of cancer treatment adding to traditional chemotherapy in the first and subsequent lines. As a relatively new drug class and based on the nature of cancer as an immune mediated disease, occasional use of ICIs outside their approved indication might occur based on multiple reasons. These include the complexity of cancer and its treatment approaches, rare cancer types that are hard to study, variety of cancer subtypes and stages that require different treatment protocols and combinations and the need to use new medications in metastatic patients who progress after exhaustion of all indicated treatment lines.

The National Center for Cancer Care & Research (NCCCR) is the only center that serves adult cancer patients in the State of Qatar. Although the NCCCR strictly applies evidence-based medicine, we still face some situations that require the use of cancer drugs out of the approved indications by Food and Drug Administration (FDA) or European Medicines Agency (EMA), due to the above-mentioned reasons. Therefore, we have developed a standardized methodology of requesting, reviewing, and approving the use of cancer drugs outside the approved indications. We have conducted a retrospective study to assess the efficacy and safety of all ICIs used outside the approved indications by FDA or EMA in the NCCCR over the duration of 4.5 years.

We found that 26% of ICIs use was off-label; 836 cycles for 103 patients. The efficacy outcomes were not that promising with 65% of patients having progressed disease. This may be explained by the fact that most patients used ICIs after exhausting multiple lines. Moreover, the safety data showed that 35% of patients had immune-related adverse events (irAEs), and that half of those had severe irAEs which required treatment interruption or discontinuation. Remarkably, we noticed that the most common reported irAEs amongst our population were hepatic toxicities, thyroid toxicities, and hematological toxicities which are different from published literature. As it is well-known, ICIs are very expensive drugs and so such treatment failure rates in addition to high costs of toxicity management increase the financial burden on healthcare systems.

ICIs would probably be proved efficacious in more cancer indications yet to be approved. However, the use of ICIs outside the approved indications might not be the most effective, safe, or efficient option considering the high probability of disease progression, increased risk of irAEs, and potential waste of resources. Therefore, the off-label use of ICIs should be limited to very selected cases with strict selection criteria and close patient follow-up. 


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