High-Throughput Genomics and Clinical Outcome in Hard-to-Treat Advanced Cancers: Results of the MOSCATO 01 Trial

Abstract

High-throughput genomic analyses may improve outcomes in patients with advanced cancers. MOSCATO 01 is a prospective clinical trial evaluating the clinical benefit of this approach. Nucleic acids were extracted from fresh-frozen tumor biopsies and analyzed by array comparative genomic hybridization, next-generation sequencing, and RNA sequencing. The primary objective was to evaluate clinical benefit as measured by the percentage of patients presenting progression-free survival (PFS) on matched therapy (PFS2) 1.3-fold longer than the PFS on prior therapy (PFS1). A total of 1,035 adult patients were included, and a biopsy was performed in 948. An actionable molecular alteration was identified in 411 of 843 patients with a molecular portrait. A total of 199 patients were treated with a targeted therapy matched to a genomic alteration. The PFS2/PFS1 ratio was >1.3 in 33% of the patients (63/193). Objective responses were observed in 22 of 194 patients (11%; 95% CI, 7%-17%), and median overall survival was 11.9 months (95% CI, 9.5-14.3 months). This study suggests that high-throughput genomics could improve outcomes in a subset of patients with hard-to-treat cancers. Although these results are encouraging, only 7% of the successfully screened patients benefited from this approach. Randomized trials are needed to validate this hypothesis and to quantify the magnitude of benefit. Expanding drug access could increase the percentage of patients who benefit. .

The SHIVA01 trial: what have we learned?

“…Patients in SHIVA01 were allowed to cross over at disease progression in either arm. The propor tion of patients who had a PFS2toPFS1 ratio exceed ing 1.3 in the subgroup of patients who crossed over in SHIVA01 compared favorably with the results obtained from the von Hoff study and in MOSCATO (37 vs 27 and 33%) [13,16,18].…”

“…The results of the prospective randomized SHIVA01 did not confirm the hypotheses generated by nonran domized clinical studies, including the pilot study by von Hoff et al [13], the experience from the MD Ander son Cancer Center [14,15] and the MOSCATO trial [16]. All these three studies also belong to algorithmtesting studies in the sense they were not powered to assess the efficacy of a specific drug in a specific subgroup of patients.…”

Cancer : les trois époques de la médecine personnalisée

“…Le taux de faillite personnelle est près de trois fois plus élevé chez ces patients que dans la population générale [7]. 6 L'approbation par NICE suppose un coût par QUALY inférieur à 50 000 £ (environ 55 000 €). purposes, then by sequencing of tumour DNA in order to define and apply targeted therapies.…”

“…Elles suscitent de très nombreux essais et représentent un progrès très significatif, d'autant que l'espoir existe de les rendre assez généralement applicables en les combinant à d'autres approches (radiothérapies ou thérapies ciblées [11]) (➜). 6 [12]. C'est une forme de rationnement, qui présente l'avantage d'être relativement rationnelle et transparente, et qui permet d'exercer une certaine pression sur les entreprises pharmaceutiques, mais qui n'en est pas moins difficile à accepter pour les malades… Les nouveaux moyens de la génomique ont donc autorisé des avancées considérables dans la connaissance des mécanismes du cancer et provoqué d'importants changements de perspective ; on ne peut pas encore dire que la « Guerre contre le cancer » ait été gagnée, mais des progrès significatifs ont eu lieu comme en témoigne la baisse générale de la mortalité pour quasiment tous les cancers [13] (➜).…”

At the dawn of personalized reproductive medicine: opportunities and challenges with incorporating multigene panel testing into fertility care

“…Today, oncologists routinely categorize tumors based on genetic signatures and refine their treatment strategies accordingly. This targeted approach to more personalized treatment has led to significantly higher progression-free survival rates when compared to the outcomes of conventional therapies [2]. Knowledge of patients' genetic risk factors has also decreased patient morbidity and mortality by more precisely revealing individuals who would benefit from preventative cancer screenings such as colonoscopies or mammograms.…”