Longer survival with precision medicine in late-stage cancer patients☆

Abstract

Background

In a per-protocol analysis of molecularly profiled patients with treatment-refractory, end-stage cancer discussed at the National Molecular Tumor Board (NMTB), we aimed to assess the overall survival (OS) outcome of targeted treatment compared with no targeted treatment.

Materials and methods

Patients were prospectively included at a single oncological center. Whole exome and RNA sequencing (tumor-normal) were carried out, and cases were presented at the NMTB for discussion of targeted treatment. Treatment was available through a basket trial, by compassionate use or in early clinical trials.

Results

One hundred and ninety-six patients were included from 2020 to 2023. In all but three patients a driver variant was disclosed, while 42% had simultaneous affection of more than three oncogenic pathways. In 42% of patients a druggable target was identified but two-thirds did not receive the suggested treatment. The fraction of patients initiating treatment yearly rose from 8% to 22%. For patients treated ( N = 30), the clinical benefit rate was 44% and median time on treatment was 3.5 months. Druggable targets were enriched in lung cancers, while patients receiving or not receiving targeted treatment had similar clinical characteristics. The median OS was longer for patients receiving targeted treatment (15 months), but similar for patients with no druggable target and suggested targeted treatment not initiated (5 and 6 months, respectively) ( P = 0.004). In multivariate analysis, targeted treatment (hazard ratio 0.43, confidence interval 0.25-0.72), few metastatic sites, and adenocarcinoma histology were predictive of improved OS while alterations of the RTK/RAS pathway were prognostically unfavorable.

Conclusions

Tissue-agnostic targeted treatment based on molecular tumor profiling is possible in an increasing fraction of end-stage cancer patients. In those who receive targeted treatment, results strongly suggest a significant survival benefit.

Highlights

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  Impact on patients’ (pts) survival is rarely reported in tissue-agnostic studies of precision medicine.

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  In 196 end-stage cancer pts, we assessed the OS of those treated or not treated with a matched targeted drug.

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  Druggable targets were suggested in 42% but 2/3 were not treated. Median time to treatment failure was 3.5 months.

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  Pts treated with a matched drug survived 2.6× longer. Targeted treatment was the strongest prognostic predictor.

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  The results strongly suggest a survival benefit of precision medicine even in the setting of end-stage cancer.