Feasibility and outcome of genomics-guided treatment selection in advanced cancer – the MEGALiT explorative clinical trial
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...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Medical Journals Sweden
2025-06-01
|
| Series: | Acta Oncologica |
| Subjects: | |
| Online Access: | https://medicaljournalssweden.se/actaoncologica/article/view/43366 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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.
|
|---|---|
| ISSN: | 1651-226X |