First Nationwide Molecular Screening Program in Spain for Patients With Advanced Breast Cancer: Results From the AGATA SOLTI-1301 Study.

Sònia Pernas ,Paolo Nuciforo,Antonio Llommbard-Cussac,Juan Miguel Cejalvo,Joan Dorca,Tomás Pascual,Aleix Prat,Jordi Canes,Marta Dueñas,Antonia Perelló,Ana Vivancos,Mafalda Oliveira,Patricia Villagrasa,Eva Ciruelos,Laia Paré,Inmaculada Rapado,Maurizio Scaltriti,G Ribas ,María Vidal ,Álvaro Montaño ,Jordi Rodón ,Octavio Burgués

doi:10.3389/fonc.2021.744112

Abstract

BackgroundThe SOLTI-1301 AGATA study aimed to assess the feasibility of a multi-institutional molecular screening program to better characterize the genomic landscape of advanced breast cancer (ABC) and to facilitate patient access to matched-targeted therapies in Spain.MethodsDNA sequencing of 74 cancer-related genes was performed using FFPE tumor samples in three different laboratories with three different gene panels. A multidisciplinary advisory board prospectively recommended potential targeted treatments. The primary objective was to determine the success of matching somatic DNA alteration to an experimental drug/drug class.ResultsBetween September 2014 and July 2017, 305 patients with ABC from 10 institutions were enrolled. Tumor sequencing was successful in 260 (85.3%) patients. Median age was 54 (29-80); most tumors were hormone receptor-positive/HER2-negative (74%), followed by triple-negative (14.5%) and HER2-positive (11.5%). Ninety-seven (37%) tumor samples analyzed proceeded from metastatic sites. Somatic mutations were identified in 163 (62.7%) patients, mostly in PIK3CA (34%), TP53 (22%), AKT1 (5%), ESR1 (3%), and ERBB2 (3%) genes. Significant enrichment of AKT1 mutation was observed in metastatic versus primary samples (9% vs. 2%; p=0.01). Genome-driven cancer therapy was recommended in 45% (n=116) of successfully screened patients, 11% (n=13) of whom finally received it. Among these patients, 46.2% had a PFS of ≥6 months on matched therapy.ConclusionsAGATA is the first nationwide molecular screening program carried out in Spain and we proved that implementing molecular data in the management of ABC is feasible. Although these results are promising, only 11% of the patients with genome-driven cancer therapy received it.

Highlights

The SOLTI-1301 AGATA study aimed to assess the feasibility of a multiinstitutional molecular screening program to better characterize the genomic landscape of advanced breast cancer (ABC) and to facilitate patient access to matched-targeted therapies in Spain
Results from tumoral DNA sequencing were evaluated by a molecular advisory tumor board (MAB) comprised of medical oncologists, pathologists, and molecular biologists
If an actionable molecular alteration was found, meaning that it was considered potentially responsive to targeted therapy, the MAB reviewed the anonymized medical history of the patient, in collaboration with each treating physician, and proposed matched targeted therapies

Summary

Introduction

The SOLTI-1301 AGATA study aimed to assess the feasibility of a multiinstitutional molecular screening program to better characterize the genomic landscape of advanced breast cancer (ABC) and to facilitate patient access to matched-targeted therapies in Spain. Comprehensive molecular profiling of breast cancers revealed that 80.4% of tumors harbor a genomic mutation in at least one of eight pathways with potential treatment implications [7]. As the number of targeted drugs increases and tumor genomic sequencing technologies become more available, genome-driven cancer treatment has substantially grown as a potential strategy of precision medicine [9,10,11], but costs and complexity of this technologies generally limit the access of this approach to just a minority of patients in the real clinical practice

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Results

Conclusion