Do more targets allow more cancer treatments, or not?

Area of Science:

• Oncology
• Genomics
• Regulatory Science

Background:

• Current oncology treatment models (histological, agnostic, mutational) differ in clinical, technological, and organizational aspects, impacting regulatory procedures and patient access to antineoplastic therapies.
• Histological and agnostic models rely on regulatory agency authorization for targeted therapies based on tumor type or specific genetic mutations.
• The mutational model identifies molecular alterations via next-generation sequencing but faces challenges due to uncertain drug efficacy and toxicity, precluding standard regulatory pathways.

Purpose of the Study:

• To analyze the regulatory differences and implications for patient access across histological, agnostic, and mutational oncology models.
• To highlight the need for standardized multidisciplinary approaches, such as molecular tumor boards (MTBs), in the mutational model.
• To address the lack of real-world evidence (RWE) in the mutational model and propose solutions for therapy access.

Main Methods:

• Comparative analysis of regulatory procedures for different oncology models.
• Identification of challenges in the mutational model, including the need for multidisciplinary expertise (e.g., MTBs).
• Discussion of the necessity for real-world evidence (RWE) from clinical practice, contrasting with limited clinical trial data.

Main Results:

• The mutational model requires specialized multidisciplinary input (MTBs) for drug-genomic profile matching, but standardization is lacking.
• Significant gaps exist in real-world evidence (RWE) for therapies selected through the mutational model.
• Existing Italian regulatory frameworks (managed-entry agreements, drug monitoring registries) offer potential pathways for accessing therapies identified by the mutational model.

Conclusions:

• The mutational oncology model presents unique regulatory hurdles requiring standardized multidisciplinary decision-making and robust RWE.
• An indication-value-based sub iudice authorization procedure is proposed as a potential solution for accessing mutational model-selected therapies.
• The Italian healthcare system can leverage existing regulatory mechanisms to facilitate patient access to precision oncology treatments identified through extensive molecular profiling.