ESMO 2017 : Old drugs can be repositioned on a target-specific basis by systematic DNA sequencing: results from a national Dutch trial


  • Oncology Conference Roundups
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Takeaway

  • Whole genome sequencing can identify new treatments for patients with no standard treatment and help to reposition old drugs.

Why this matters

  • Whole genome sequencing, when performed on many patients, allows finding commonalities between tumours and gene mutations.
  • Access to genetically matched drugs, even when approved for other indications, can be granted by programs like the Drug Rediscovery Protocol developed in the Netherlands.

Study design

  • Patients with solid tumours, glioblastoma, lymphoma, or multiple myeloma are enrolled in multiple parallel cohorts, each defined by 1 tumour type, 1 tumour profile, and 1 treatment.
  • Efficacy is analysed per cohort aimed at ≥1 clinical benefit (complete response; partial response; or stable disease ≥16 weeks) on 8 patients in stage I and ≥5 on 24 patients in stage II.
  • Tumour biopsy for biomarker research is performed.
  • The study involved 23 participating hospitals.
  • Drug Rediscovery Protocol is built upon 19 study drugs.
  • Funding: Barcode for Life Foundation (BFL; Dutch Cancer Society (KWF); Hartwig Medical Foundation (HMF); Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Novartis, Roche).

Key results

  • The study was launched in September 2016.
  • 250 cases have been submitted to the protocol, 1/3 have been treated.
  • 37% of the patients treated showed clinical benefits (6% complete response, 14% partial response, 17% stable disease ≥16 weeks).
  • 18% of the cases were rejected because of ineligibility (mainly because of unavailability of matching drug studies in the Drug Rediscovery Protocol or no target-drug-match).

Limitations

  • The effect of the whole genome sequencing would be greater if more drugs were included in the Drug Rediscovery Protocol.

Expert comment

  • Dr. Richard Marais, from the Cancer Research UK Manchester Institute said:whole genome sequencing is very expensive, so the trial needs to show that it can be cost-effective and work for patients. Stratifying even 10% of trial participants could make the process cost-neutral: for health systems, this would mean that despite a high upfront investment, the downstream benefits to patients and potential reduction of the cost of treating them would be enormous. In this context, the numbers being presented here are very impressive. They have definitely shown a proof of principle.”