Off-label drug use in oncology: integrating molecular and genetic analysis in an academic center’s real-world approach

Abstract

Background

Recent advancements in cancer treatment have shifted the paradigm from chemotherapy to targeted therapies and immunotherapies, proving effective even in early-stage cancers. Regulatory agencies like the Food and Drug Administration, European Medicines Agency, and Italian Agency for Drugs have approved several targeted therapies for specific genetic mutations, significantly improving outcomes for several diseases. These advancements highlight the importance of identifying molecular targets, even in historically difficult-to-treat cancers.

Materials and methods

A retrospective observational study was conducted at the University of Campania “Luigi Vanvitelli” from January 2015 to January 2022, involving 83 adult patients with solid tumors. Patients received off-label drugs at no cost. The study analyzed treatment and pathology data, focusing on progression-free survival (PFS) and overall survival (OS), using Kaplan–Meier estimates and the log-rank test for statistical analysis.

Results

Patients averaged 63 years old, with a slight male majority. Off-label drugs were primarily requested for upper gastrointestinal cancers (42%) and colorectal carcinoma (21%). The most common molecular testing method was next-generation sequencing (NGS). Immunotherapy was the predominant treatment (67%), followed by targeted therapy and chemotherapy. The median PFS was 3.4 months [95% confidence interval (CI) 2.0-4.5 months], and the median OS was 10 months (95% CI 7.5-12.2 months). Early-line off-label treatment showed a trend toward longer PFS compared with later lines.

Conclusion

Early access to off-label drugs, particularly for patients with specific genetic alterations, can improve outcomes. The study underscores the importance of molecular tumor boards and multidisciplinary collaboration in selecting off-label treatments. Despite regulatory and ethical challenges, off-label drug use offers significant therapeutic opportunities, necessitating well-designed clinical trials and registries to better understand their efficacy and safety.