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. 2025 Jun 4:64:742-750.
doi: 10.2340/1651-226X.2025.43366.

Feasibility and outcome of genomics-guided treatment selection in advanced cancer - the MEGALiT explorative clinical trial

Lars Ny  1 , Henrik Fagman  2 , Johan Botling  3 , Loviisa Mantovaara  4 , Peter Asplund  5 , Hannah Karlsson  5 , Jennie Aust  1 , Edvard Abel  1 , Mats Hellström  4 , Joakim Crona  6 , Peter Nygren  7
Affiliations

Feasibility and outcome of genomics-guided treatment selection in advanced cancer - the MEGALiT explorative clinical trial

Lars Ny et al. Acta Oncol. .

Abstract

Background: Precision cancer medicine (PCM) is key to advancing cancer treatment beyond the standard of care. We performed an explorative clinical trial, MEGALiT, to investigate the feasibility, safety, and clinical benefit of genomics-based PCM in advanced cancer.

Methods: MEGALiT recruited adult patients with advanced solid tumors refractory to standard treatment. Tumor DNA from newly acquired biopsies or ctDNA were analyzed for alterations targetable with the PD-L1 inhibitor atezolizumab, the MEK inhibitor cobimetinib, the mTOR inhibitor everolimus, or the PARP-inhibitor niraparib. Any other 'in study' treatment was left to the discretion of the physician.

Results: Outcome data are reported for 153 patients. The median age was 65 years and the most common diagnoses were colorectal, prostate, and ovarian cancer. The median time from study inclusion to the Molecular Tumor Board was 35 days for tumor sampling by biopsy and 21 days by ctDNA. Of the 44 patients allocated to a study drug, 38 started treatment. The median follow-up was 1.9 years. Of the patients on a study drug and evaluable for tumor response, 6% (2/32) had partial remission, and 25% (8/32) had disease control at 16 weeks. Median overall survival for patients starting a study drug was longer, 7.4 months, compared to 2.7 months for the 61 untreated patients (HR 0.43; log-rank p < 0.0001), but shorter than for the 50 patients receiving treatment of physician's choice, 11.8 months (HR 0.55; log-rank p = 0.012). No significant procedure- or drug-related severe adverse events were observed.

Interpretation: Genomics-guided treatment selection in advanced cancer is feasible and safe. However, evidence of patient benefit warrants further investigation.

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Conflict of interest statement

The authors report no competing interests related to the study.

Figures

Figure 1
Figure 1
Overview of patient treatment status while in study.
Figure 2
Figure 2
Kaplan–Meier estimates of overall survival in all patients included (A); patients allocated to a study drug and treated and patients not allocated to a study drug (B); patients allocated to a study drug and treated, patients not allocated to a study drug but treated, and patients not treated while in study (C).
Figure 3
Figure 3
Progression-free survival (PFS) for the indicated patient groups for treatment immediately prior to study inclusion (A), treatment while in study (B), and treatment after the study (C). Panel D shows number of patients with a PFS within study/PFS prior to study inclusion ratio of ≥ and < 1.3.
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