50P - Clinical impact of actionable molecular variants disclosed in late-stage cancer patients by tumor whole-exome sequencing in a prospective single-institution study

Background

In 2020 we initiated a 10-year precision medicine program based on in-house whole exome sequencing (WES) and RNA sequencing (RNAseq) at Aalborg University Hospital, Denmark - a midsize, regional public academic hospital. Here we present updated results of the clinical impact in the first three years.

Methods

We included 236 eligible, adult patients with late-stage cancer of any diagnosis from June 2020 to May 2023 in the Proseq Cancer trial. Molecular profiling of new or fresh frozen tumor biopsies was done by WES and RNAseq with parallel sequencing of non-tumoral DNA as individual reference. Cases were presented at the National Molecular Tumor Board (NMTB) for discussion of targeted treatment. Treatment was available through a multicenter basket trial (Protarget, NCT04341181), phase I-trials, or by compassionate/off label use.

Results

A targeted treatment was suggested for 72 patients (31%) at the NMTB. Of these, 23 patients initiated treatment and 11 patients are still waiting for treatment. Reasons for no treatment were: patients general condition worsened (22 patients), no available drug (6 patients), patient declined (6 patients), and prior treatment against same target (4 patients). A total of 27 treatments were initiated, most commonly targeted against ERBB2, TMB-high, MSI, BRCA/ATM and BRAF-V600E. The response rate was 44% (among 18 evaluable), and the clinical benefit rate was 52% (among 23 evaluable). Median treatment duration was 3 months (range, 2 weeks to +2 years). The median overall survival from the date of NMTB was 6, 6 and 15 months, respectively, for patients with no recommendation of targeted treatment, with recommended targeted treatment not initiated, and with recommended targeted treatment initiated (P=0.01).

Conclusions

Precision medicine in end-stage cancer patients is feasible in a regional academic hospital through close collaboration with comprehensive cancer centers and nationwide access to drug trials. Although efficacy of targeted treatments is encouraging, the overall clinical impact in this poor prognosis population is modest.

Editorial acknowledgement

Clinical trial identification

NCT05695638; January 25, 2023.

Legal entity responsible for the study

M. Ladekarl.

Funding

The Council of the North Denmark Region and H.E. & N.C. Brogaards Legat til Kræftforskningens Fremme.

Disclosure

All authors have declared no conflicts of interest.