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Comparative Study
. 2021 Oct;125(9):1261-1269.
doi: 10.1038/s41416-021-01502-x. Epub 2021 Sep 7.

Molecular profiling of advanced solid tumours. The impact of experimental molecular-matched therapies on cancer patient outcomes in early-phase trials: the MAST study

Valentina Gambardella #  1   2 , Pasquale Lombardi #  3 , Juan Antonio Carbonell-Asins  4 , Noelia Tarazona  1   2 , Juan Miguel Cejalvo  1 , Inés González-Barrallo  1 , Jorge Martín-Arana  1   2   4 , Roberto Tébar-Martínez  1   5   6 , Alba Viala  1 , Gema Bruixola  1 , Cristina Hernando  1 , Inma Blasco  1 , Federica Papaccio  7 , Carolina Martínez-Ciarpaglini  2   8 , Clara Alfaro-Cervelló  2   8 , Enrique Seda-García  5   6 , Sebastián Blesa  5   6 , Isabel Chirivella  1 , Josefa Castillo  2   9 , José Vicente Montón-Bueno  1 , Susana Roselló  1   2 , Marisol Huerta  1 , Alejandro Pérez-Fidalgo  1 , Paloma Martín-Martorell  1 , Amelia Insa-Mollá  1 , Tania Fleitas  1   2 , Pilar Rentero-Garrido  5 , Sheila Zúñiga-Trejos  4 , Andrés Cervantes  10   11 , Desamparados Roda  12   13
Affiliations
Comparative Study

Molecular profiling of advanced solid tumours. The impact of experimental molecular-matched therapies on cancer patient outcomes in early-phase trials: the MAST study

Valentina Gambardella et al. Br J Cancer. 2021 Oct.

Abstract

Introduction: Molecular-matched therapies have revolutionized cancer treatment. We evaluated the improvement in clinical outcomes of applying an in-house customized Next Generation Sequencing panel in a single institution.

Methods: Patients with advanced solid tumors were molecularly selected to receive a molecular-matched treatment into early phase clinical trials versus best investigators choice, according to the evaluation of a multidisciplinary molecular tumor board. The primary endpoint was progression-free survival (PFS) assessed by the ratio of patients presenting 1.3-fold longer PFS on matched therapy (PFS2) than with prior therapy (PFS1).

Results: Of a total of 231 molecularly screened patients, 87 were eligible for analysis. Patients who received matched therapy had a higher median PFS2 (6.47 months; 95% CI, 2.24-14.43) compared to those who received standard therapy (2.76 months; 95% CI, 2.14-3.91, Log-rank p = 0.022). The proportion of patients with a PFS2/PFS1 ratio over 1.3 was significantly higher in the experimental arm (0.33 vs 0.08; p = 0.008).

Discussion: We demonstrate the pivotal role of the institutional molecular tumor board in evaluating the results of a customized NGS panel. This process optimizes the selection of available therapies, improving disease control. Prospective randomized trials are needed to confirm this approach and open the door to expanded drug access.

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Conflict of interest statement

AC declares institutional research funding from Genentech, Merck Serono, BMS, MSD, Roche, Beigene, Bayer, Servier, Lilly, Novartis, Takeda, Astellas, Takeda, Natera and Fibrogen and advisory board or speaker fees from Angem, Merck Serono, Roche, Bayer, Servier and Pierre Fabre in the past 5 years. All remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Consort diagram.
The flowchart showes the subject enrollment and treatment allocation.
Fig. 2
Fig. 2. Most common genomic alterations detected with our in-house NGS customised panel.
This graph shows the percentage (left) and absolute frequency (right) of genomic alterations detected across the study subjects. NGS next-generation sequencing.
Fig. 3
Fig. 3. Schematic representation of our Molecular Tumour Board.
The picture summarizes the process which leads to the identification of new potential candidates for experimental therapies based on molecular analysis.
Fig. 4
Fig. 4. Outcome analyses of the included population: PFS2, PFS1, PFS2/PFS1 ratio and further lines beyond progression.
a Progression-free survival after inclusion in the trial (PFS2) was compared for molecular-matched therapy vs standard of care. b PFS derived from the previous therapy for the patients into the two groups. c PFS2/PFS1 ratio in the experimental arm with a vertical line showing 1.3 as the cutoff. d Number of further treatment lines received by the patients beyond progression in the two groups.
See this image and copyright information in PMC

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