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

OBJECTIVE: To describe the characteristics and the survival of patients with cancer with intended off-label use (OLU) cancer treatment and reimbursement request. DESIGN: Cohort study using medical record data. SETTING: Three major cancer centres in Switzerland. PARTICIPANTS: 519 patients with cancer and a reimbursement request for OLU between January 2015 and July 2018. MAIN OUTCOMES: Characteristics 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. RESULTS: OLU 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)). CONCLUSION: Contrary 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.

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

Importance: In many health systems, access to off-label drug use is controlled through reimbursement restrictions by health insurers, especially for expensive cancer drugs. Objective: To determine whether evidence from randomized clinical trials is associated with reimbursement decisions for requested off-label use of anticancer drugs in the Swiss health system. Design, Setting, and Participants: This cross-sectional study used reimbursement requests from routinely collected health records of 5809 patients with drug treatment for cancer between January 2015 and July 2018 in 3 major cancer centers, covering cancer care of approximately 5% of the Swiss population, to identify off-label drug use. For each off-label use indication with 3 or more requests, randomized clinical trial evidence on treatment benefits was systematically identified for overall survival (OS) or progression-free survival (PFS). Data were analyzed from August 2018 to December 2020. Exposures: Available randomized clinical trial evidence on benefits for OS or PFS for requested off-label use indications. Main Outcomes and Measures: The main outcome was the association between evidence for treatment benefit (expressed as improved OS or PFS) and reimbursement in multivariable regression models. Results: Among 3046 patients with cancer, 695 off-label use reimbursement requests in 303 different indications were made for 598 patients (median [interquartile range] age, 64 [53-73] years; 420 [60%] men). Off-label use was intended as first-line treatment in 311 requests (45%). Reimbursement was accepted in 446 requests (64%). For 71 indications, including 431 requests for 376 patients, there were 3 or more requests. Of these, 246 requests (57%) had no supporting evidence for OS or PFS benefit. Reimbursement was granted in 162 of 246 requests without supporting evidence (66%). Of 117 requests supported by OS benefit, 79 (67%) were reimbursed, and of 68 requests supported by PFS benefit alone, 54 (79%) were reimbursed. Evidence of OS benefit from randomized clinical trials was not associated with a higher chance of reimbursement (odds ratio, 0.76, 95% CI, 0.45-1.27). Conclusions and Relevance: These findings suggest that in a health care system enabling access to off-label use, it was frequently intended as a first-line treatment in cancer care. Availability of randomized clinical trial evidence showing survival benefit was not associated with reimbursement decisions for off-label anticancer drug treatment in Switzerland. A transparent process with criteria considering clinical evidence is needed for evidence-based reimbursement decisions to ensure fair access to cancer treatments.

Contrasting evidence to reimbursement reality for off-label use (OLU) of drug treatments in cancer care: rationale and design of the CEIT-OLU project.

Background: Off-label use (OLU) of a drug reflects a perceived unmet medical need, which is common in oncology. Cancer drugs are often highly expensive and their reimbursement is a challenge for many healthcare systems. OLU is frequently regulated by reimbursement restrictions. For evidence-based healthcare, treatment ought to be reimbursed if there is sufficient clinical evidence for treatment benefit independently of patient factors not related to the treatment indication. However, little is known about the reality of OLU reimbursement and its association with the underlying clinical evidence. Here, we aim to investigate the relationship of reimbursement decisions with the underlying clinical evidence. Methods/ design: We will extract patient characteristics and details on treatment and reimbursement of cancer drugs from over 3000 patients treated in three Swiss hospitals. We will systematically search for clinical trial evidence on benefits associated with OLU in the most common indications. We will describe the prevalence of OLU in Switzerland and its reimbursement in cancer care, and use multivariable logistic regression techniques to investigate the association of approval/rejection of a reimbursement requests to the evidence on treatment effects and to further factors, including type of drug, molecular predictive markers and the health insurer. Discussion: Our study will provide a systematic overview and assessment of OLU and its reimbursement reality in Switzerland. We may provide a better understanding of the access to cancer care that is regulated by health insurers and we hope to identify factors that determine the level of evidence-based cancer care in a highly diverse western healthcare system.