Pancreatic cancer: homologous recombination mutation identifies platinum therapy candidates

  • Park W & al.
  • Clin Cancer Res
  • 22 May 2020

  • curated by Deepa Koli
  • Univadis Clinical Summaries
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Takeaway

  • In patients with advanced pancreatic cancer who receive firstline platinum treatment, a germline or somatic homologous recombination (HR) mutation is associated with improved survival.

Why this matters

  • Identification of a validated biomarker can help select patients who are most suitable for platinum therapy.

Study design

  • 262 patients (median age, 64 years) were identified for the final analysis who had undergone both germline and somatic MSK-IMPACT (Memorial Sloan Kettering integrated mutation profiling of actionable cancer targets) analysis.
  • Funding: MSK Cancer Center; others.

Key results

  • Median follow-up was 21.9 years.
  • No difference was seen in germline and somatic HR mutations; therefore, both groups were designated as HR-deficient (HRD).
  • Patients with HR deficiency showed significant improvement in OS vs those without (HR, 0.50; P<.01>
  • PFS was significantly longer in patients with HRD who received firstline platinum vs those who did not (12.6 vs 4.4 months).
  • Patients with HRD who were treated with firstline platinum had a significantly lower risk for progression or death vs those without HRD (HR, 0.44; P<.01>
  • In patients with mutations in both gene copies, platinum-based chemotherapy was associated with longer PFS vs other therapies (13.3 vs 3.8 months; P<.0001>
  • Biallelic (11%) and core HR mutations (12%) had higher genomic instability and were associated with improved PFS on firstline platinum vs nonplatinum therapy.

Limitations

  • Small subgroups.