Association of Supporting Trial Evidence and Reimbursement for Off-Label Use of Cancer Drugs

Herbrand, Amanda K.; Schmitt, Andreas M.; Briel, Matthias; Ewald, Hannah; Goldkuhle, Marius; Diem, Stefan; Hoogkamer, Anouk; Joerger, Markus; Moffa, Giusi; Novak, Urban; Hemkens, Lars G.; Kasenda, Benjamin

doi:10.1001/jamanetworkopen.2021.0380

Cited by 14 publications

(17 citation statements)

References 26 publications

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“…Swissmedic approved nivolumab for this indication 1 year later in August 2018. Within this year, nivolumab was requested 14 times as OLU for the adjuvant treatment of localised melanoma in our cohort (see also Herbrand et al 4). Another example is pembrolizumab, which was requested nine times as first-line treatment for metastatic non-small lung cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Whether the use of a drug is off-label may vary across different countries and can change over time 3. In Switzerland, about 20% of patients with cancer are treated at least once with OLU 4. Situations in which OLU is intended include those when heavily pretreated patients do not have any further approved treatment option,5 or when randomised evidence for new and beneficial treatment options becomes available but formal approval is pending,6 7 or when treatment strategies from other cancer types are extrapolated to the specific case 8.…”

Section: Introductionmentioning

confidence: 99%

“…Typically, OLU is perceived as last option in situations when approved therapies are exhausted 9–11. However, we have recently shown that 45% of all reimbursement requests for OLU in Switzerland were for first-line therapies 4…”

Section: Introductionmentioning

confidence: 99%

“…An upfront reimbursement request is issued by the treating physician and the reimbursement decision is made on a case-by-case basis. While most patients in Switzerland get reimbursement and therefore access to OLU, the decisions seem arbitrary and were not associated with the underlying evidence on treatment benefits in a systematic analysis of the supporting evidence 4…”

Section: Introductionmentioning

confidence: 99%

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Characteristics and survival of patients with cancer with intended off-label use—a cohort study

et al. 2022

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ObjectiveTo describe the characteristics and the survival of patients with cancer with intended off-label use (OLU) cancer treatment and reimbursement request.DesignCohort study using medical record data.SettingThree major cancer centres in Switzerland.Participants519 patients with cancer and a reimbursement request for OLU between January 2015 and July 2018.Main outcomesCharacteristics of patients with cancer with and without access to intended OLU. Characteristics included the Glasgow prognostic score (GPS) which includes C reactive protein and albumin and discriminates prognostic groups.ResultsOLU was intended for 519 (17%) of 3046 patients with cancer, as first-line treatment in 51% (n=264) and second-line in 31% (n=162). Of the 519 patients, 63% (n=328) were male, 63% (n=329) had solid cancer and 21% (n=111) had a haematological malignancy. Their median overall survival was 23.6 months (95% CI: 19.0 to 32.5). Access to OLU had 389 (75%) patients who were compared with patients without access on average 4.9 years younger (mean; 95% CI: 1.9 to 7.9 years), had a better overall prognosis according to the GPS (51% with GPS of 0 vs 39%; OR: 1.62 (95% CI: 1.01 to 2.59)), had less frequently solid cancer (62% vs 71%; OR: 0.66 (95% CI: 0.41 to 1.05)) and advanced stage cancer (53% vs 70%; OR: 0.48 (95% CI: 0.30 to 0.75)), were more frequently treatment-naive (53% vs 43%; OR: 1.55 (95% CI 1.01 to 2.39)) and were more frequently in an adjuvant/neoadjuvant treatment setting (14% vs 5%; OR: 3.39 (95% CI: 1.45 to 9.93)). Patients with access to OLU had a median OS of 31.1 months versus 8.7 months for patients without access (unadjusted HR: 0.54; (95% CI: 0.41 to 0.70)).ConclusionContrary to the common assumption, OLU in oncology is typically not primarily intended for patients with exhausted treatment options. Patient characteristics largely differ between patients with and without access to intended OLU. More systematic evaluations of the benefits and harms of OLU in cancer care and the regulation of its access is warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Characteristics and survival of patients with cancer with intended off-label use—a cohort study

et al. 2022

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“…Herbrand, A.M. Schmitt, M. Briel, et al in years 2015-2018. Research conducted in a Swiss population demonstrated that 45% of first line treatment cases in a group of 3046 patients treated for cancer was associated with a decision to implement off-label treatment [9]. In a study published in 2021, Japanese researchers demonstrated that diseases most commonly treated off-label were sarcoma, urologic cancers, and gastrointestinal cancers [10].…”

Section: Admissibility Of Off-label Use Of Medicinal Products In Onco...mentioning

confidence: 99%

Off-label use of medicinal products in oncology: exercising due diligence or experimental activity?

Król-Całkowska¹,

Jaroszyński

2022

Nowotwory. Journal of Oncology

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One of the primary responsibilities of a physician is to diagnose and treat diseases with due diligence. Exercising due diligence in treatment process involves, among others, the use of optimal diagnostic, therapeutic and follow-up management in accordance with the current state of medical knowledge. Each medicinal product has the Summary of Product Characteristics which defines, among others, registered indications, the age group for which the product is registered, the dosing scheme, and route of administration of the product. Polish law does not refer directly to the admissibility of products that use off-label nor does it include regulations forbidding such activities. Considering a number of problems associated with products which use off-label and, on the other hand, commonness of such activities, it is necessary to introduce legal regulations defining the legitimacy and admissibility of such methods of proceeding.

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Real‐world treatment outcomes of medicines used in special situations (off‐label and compassionate use) in oncology and hematology: A retrospective study from a comprehensive cancer institution

et al. 2023

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PurposeMedicines in special situations (MSS) refer to off‐label or to unlicensed drugs under investigation (compassionate use). Our objectives were to evaluate characteristics and to estimate overall survival (OS), event‐free survival (EFS), and the duration of treatment (DT) of MSS used for cancer treatment at a multicentre comprehensive cancer institution.MethodsRetrospective cohort study on adult cancer patients for whom an MSS treatment was requested (January 2011–December 2020). A descriptive analysis was performed and median OS and EFS and 95% confidence intervals (CIs) were estimated. Survival curves were stratified by type of tumor, ECOG (Eastern Cooperative Oncology Group) performance status (PS), age, sex, treatment stage and type of drug (mechanism of action and target).ResultsTreatment was initiated in 2092 episodes (1930 patients) out of 2377 MSS episodes (2189 patients) requested, 33% for hematological treatment and 87% for advanced stage cancer. Median OS (months) was 21.1 (95% CI 19.4–22.7), median EFS was 5.6 (95% CI 5.1–6.0) months, and median DT was 4.5 [0.0; 115.3] months.OS and EFS statistically significantly favored female patients, ECOG PS ≥2 episodes showed worse OS and EFS outcomes (p < 0.0001). Statistically significant differences in survival were found within solid and hematological cancer, disease stage, drug mechanism of action, and type of cancer (p < 0.001) but not for age. Survival outcomes by tumor subtype and drug are presented both globally and separately based on disease stage.ConclusionMSS uses are practiced across almost all cancer types, mostly for advanced disease. ECOG PS ≥2, along with advanced disease, was related to worse survival. Information about real‐world outcomes is valuable and contributes to better decision‐making regarding MSS and our experience in this field could be of interest for other colleagues.

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Association of Supporting Trial Evidence and Reimbursement for Off-Label Use of Cancer Drugs

Cited by 14 publications

References 26 publications

Characteristics and survival of patients with cancer with intended off-label use—a cohort study

Characteristics and survival of patients with cancer with intended off-label use—a cohort study

Off-label use of medicinal products in oncology: exercising due diligence or experimental activity?

Real‐world treatment outcomes of medicines used in special situations (off‐label and compassionate use) in oncology and hematology: A retrospective study from a comprehensive cancer institution

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