Molecular profiling of "exceptional responders" to cancer treatment is possible

  • Conley BA & al.
  • J Natl Cancer Inst
  • 27 Apr 2020

  • curated by Deepa Koli
  • Univadis Clinical Summaries
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Takeaway

  • Retrospective identification of exceptional responders to cancer treatment and molecular profiling of pretreatment archived tissue are feasible.

Why this matters

  • Accompanying editorial: “exceptional responders could help to identify novel or known molecular abnormalities that may be predictive of response to agents targeting a relevant biological pathway.”

Study design

  • The study evaluated the feasibility and potential usefulness of sequencing DNA and RNA from clinical tumor specimens from patients who had experienced unusually profound or durable responses to systemic therapy.
  • 117 cases of exceptional responders with analyzable tissue were identified.
  • Criteria for exceptional responses:
    • Expected complete or partial response (n=37);
    • Exceptionally long response (n=54); and
    • Both criteria (n=26).
  • Funding: National Cancer Institute.

Key results

  • Treatment:
    • Combination chemotherapy regimens (n=80);
    • Antiangiogenesis agents with or without additional chemotherapy (n=34); and
    • Immune checkpoint inhibitors (n=6).
  • Potential clinically relevant germline mutations were found in 6 tumors:
    • Pathogenic BRCA1/2 mutations were found in patients with breast cancer (n=2), NSCLC (n=1), and rectal cancer (n=1). 
    • 1 patient with breast cancer had a known pathogenic BRCA1 germline mutation and another had a likely germline mutation in CHEK2.
    • 1 patient with a poorly differentiated lung cancer and history of breast cancer had a PALB2 mutation.

Limitations

  • Retrospective.