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Poly (ADP-Ribose) Polymerase Inhibitors in Patients With Urothelial Cancer

Teresa Gamba1, Jessica Paparo1, Olimpia Panepinto1

  • 1Department of Oncology, University of Turin, AO Ordine Mauriziano Hospital, Turin, Italy.

Clinical Genitourinary Cancer
|July 27, 2023
PubMed

Insights

Poly ADP-ribose polymerase inhibitors (PARPis) show promise in urothelial cancer (UC) maintenance therapy, especially when combined with immune-checkpoint inhibitors (ICIs) in platinum-naïve patients. Prior selection for homologous recombination repair deficiency (HRD) is crucial for identifying potential beneficiaries.

Area of Science:

  • Oncology
  • Genitourinary Cancers
  • Cancer Therapeutics

Background:

  • Poly ADP-ribose polymerase inhibitors (PARPis) demonstrate clinical efficacy across various cancers.
  • Urothelial cancer (UC) presents a rationale for PARPi use due to high homologous-recombination repair deficiency (HRD) rates and potential platinum-based chemotherapy (PBCT) cross-sensitivity.

Purpose of the Study:

  • To review and analyze clinical trials investigating PARPi activity in UC.
  • To identify patient subgroups likely to benefit from PARPis, optimal treatment settings, and the impact of combining PARPis with immune-checkpoint inhibitors (ICIs).

Main Methods:

  • Comprehensive review of all available trials on PARPi activity in UC across neoadjuvant, adjuvant, first-line, subsequent-line, and maintenance settings.
  • Inclusion of trials with PARPis as monotherapy and in combination with other agents.

Main Results:

  • Intriguing signals of improved progression-free survival in the maintenance setting for patients with HRR aberrations (ATLANTIS trial).
  • Negative results from Meet-URO12 suggest limitations of platinum sensitivity for patient selection.
  • Discouraging outcomes for single-agent PARPis in unselected, pretreated, chemo-refractory patients.
  • Globally negative results for PARPi and ICI combinations in the advanced setting, though trials in the platinum-naïve setting are ongoing.

Conclusions:

  • Prior selection based on HRD status is essential for identifying patients who may benefit from PARPis in UC.
  • Maintenance treatment and combination with ICIs in platinum-naïve patients appear to be the most promising clinical settings for PARPis.
  • Further trials are needed to definitively establish the role of PARPis in UC therapy.
Keywords:
NiraparibOlaparibPARP inhibitorsRucaparib

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