A Step Forward in Personalized Molecular Oncology

BARCELONA, Spain — A trial conducted across 40 Italian centers has underscored the significance of a new mutational approach to cancer research. The Rome Study, presented at the European Society for Medical Oncology (ESMO) Annual Meeting 2024, demonstrated the value of integrating comprehensive genomic profiling with case discussions by a panel of experts involved in molecular tumor boards (MTBs). This approach has enabled the selection of the most suitable therapies to improve patient outcomes.

“The Rome Study was designed to understand the rules of the game, specifically which patients should undergo profiling, how to interpret the test results, and how to identify the best treatment for each case,” said Andrea Botticelli, MD, PhD, professor of oncology at Sapienza Università di Roma and oncologist at Policlinico Umberto I in Roma, Italy, who presented the research findings.

A Precise Choice

The Rome Study, a phase 2 multi-basket randomized trial, assessed the feasibility, efficacy, and safety of targeted therapy (TT) vs the standard of care (SoC) in patients with solid tumors harboring actionable molecular alterations. These alterations were evaluated using specific tests (FoundationOne CDx and FoundationOne Liquid CDx) on solid tissue and blood samples from nearly 1800 patients with various solid tumors who had undergone no more than two previous lines of treatment.

“Following discussions with the MTBs, patients with at least one target alteration were randomized in a 1:1 ratio to TT chosen by the board or to SoC chosen by the researcher,” Botticelli explained.

In total, 400 patients were randomized, 200 to the TT group and 200 to the SoC group.

The study achieved its primary endpoint of objective response rate, with 17% in the TT group and 9.5% in the SoC group. Progression-free survival was also better in the TT group than in the SoC group, with median values of 3.7 months vs 2.8 months. At 12 months, progression-free survival rates reached 22.3% in the TT group compared with 7.5% in the SoC group. However, no significant differences were observed in overall survival between the two groups. Adverse events of grade 3 or higher occurred in 35% patients treated with TT, diarrhea and systemic infections being the most common, and in 40% patients treated with SoC, primarily neutropenia and fatigue. These differences are linked to the different drugs used in the two groups.

Precision Oncology Evolves

A key aspect of the Rome Study was the role of MTB discussions. Botticelli explained that each case was discussed, considering not only the presence of one or more actionable molecular alterations but also the clinical characteristics of the patient, histology, and potential resistances.

“The mutational model, guided by comprehensive genomic profiling and MTB activities, could help overcome some limitations of previous models and enable the selection of more effective personalized targeted therapies,” Botticelli said, explaining that studies with adaptable designs are needed to provide useful models to accelerate patient access to effective TT and to achieve personalized oncology in clinical practice.

“We must undoubtedly look at agnostic treatments, based on the presence of a specific mutation, but without forgetting histology and other factors,” added Federica Di Nicolantonio, MD, PhD, professor of oncology at the University of Turin, Turin, and oncologist at the Candiolo Cancer Institute, Candiolo, Italy, referring to the ESMO Tumour-Agnostic Classifier and Screener, a tool for assessing the agnostic potential of molecularly guided therapies and for steering drug development.

The Rome Study received funding from Roche, Novartis, Pfizer, Bristol Myers Squibb (BMS), Takeda Pharmaceutical Co., Incyte, Merck, and Eli Lilly. Botticelli disclosed receiving consultancy fees from Eli Lilly, Pfizer, Novartis, Roche, BMS, AstraZeneca, Merck Sharp & Dohme, Daiichi Sankyo, Gilead, and Seagen. Di Nicolantonio received speaker fees from Illumina, Inc. and Pierre Fabre and research funds from the Italian Association for Cancer Research and the Ministry of Health. 

Cristina Ferrario is a molecular biologist and former researcher in molecular oncology at three institutes in Milan. She has a master’s degree in communication and health from the University of Milan, Milan, and a master’s degree in cancer genetics from the University of Pavia, Pavia, Italy. She has worked as a science journalist for more than 20 years.

This story was translated from Univadis Italy, with slight adaptations, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.