Rare cancers, defined by an incidence of fewer than 6 cases per 100,000 persons per year,
constitute nearly 25% of adult malignancies. They are associated with poor patient outcomes due
to incomplete biological understanding and inadequate representation in clinical trials [1]. To
address this gap, the DKFZ/NCT/DKTK MASTER (Molecularly Aided Stratification for Tumor
Eradication Research) program, developed by NCT and DKFZ, integrates whole-genome/exome
sequencing (WGS/WES), RNA sequencing (RNA-seq), and genome-wide DNA methylation
profiling to inform clinical decision-making in patients with advanced rare cancers [2-8]. This
approach has demonstrated significant improvements in overall response rates (ORR) in 24%
and disease control rates (DCR) in 55% of cases, with a progression-free survival (PFS) ratio
greater than 1.3 in 36% of patients [4].
The objective of the randomized, multicentric, diagnostic RATIONALE trial is to evaluate the
efficacy of molecularly guided treatment versus standard treatment in patients with rare cancers
by comparing PFS between the two arms: an immediate molecular profile-informed treatment arm
(MPI arm) and a standard treatment arm with molecular profile-informed treatment upon
progression or intolerable toxicity after standard therapy (MPP arm).
