Talazoparib, Avelumab Show No Clinical Benefit in Patients With Metastatic Kidney Cancer

Some clinicians have recommended synthetic lethality with poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors for patients with a subtype of kidney cancer, including Von Hippel-Lindau (VHL)-altered clear cell renal cell carcinoma (ccRCC), fumarate hydratase (FH)- and succinate dehydrogenase (SDH)-deficient RCC, and renal medullary carcinoma (RMC), which are affected by genomic instability.

When combined with PARP inhibitors, immune checkpoint blockade (ICB) may lead to additive or synergistic effects in patients with previously treated kidney cancer.

A study from Ritesh R. Kotecha, MD, and colleagues published in European Urology Oncology analyzed the potential of a PARP inhibitor plus ICB combination in patients with treatment-refractory metastatic kidney cancer.

The primary end point was objective response rate (ORR) according to Immune Response Evaluation Criteria in Solid Tumors at 4 months. Secondary end points included progression-free survival (PFS), overall survival, and safety.

Cohort 1 comprised 10 patients with VHL-altered ccRCC who had previously received ICB. For this group, the ORR was 0, including 1 patient who was not evaluable because of missed doses. The best response was 7 patients reaching stable disease (SD). The median PFS was 3.5 months (95% CI, 1.0-3.9).

Of the 8 patients in cohort 2, 4 had FH-deficient RCC, 1 had SDH-deficient RCC, and 3 had RMC. Six patients had previously received ICB. The ORR was 0, with 2 patients achieving SD, and the median PFS was 1.2 months (95% CI, 0.4-2.9).

Across both cohorts, the most reported treatment-related adverse events included fatigue (61%), anemia (28%), nausea (22%), and headache (22%). Researchers reported 7 grade 3 to 4 events and no grade 5 events.

“The first clinical study of combination PARP [inhibitor] and ICB therapy in advanced kidney cancer did not show clinical benefit in multiple genomically defined metastatic RCC cohorts or RMC,” researchers wrote.