ATLAS: Disappointing results for rucaparib in urothelial carcinoma
medwireNews: Results of the phase 2 ATLAS trial do not support use of the PARP inhibitor rucaparib in patients with recurrent, locally advanced, or metastatic urothelial carcinoma, the investigators have reported.
“The trial had to stop prematurely because it did not meet the protocol-defined criteria for continuation,” Petros Grivas (Fred Hutchinson Cancer Research Center, Seattle, Washington, USA) told delegates at the 2020 Genitourinary Cancers Symposium in San Francisco, California, USA.
The ATLAS team gave twice-daily rucaparib 600 mg to 97 patients (78.4% men, median age 66 years) with recurrent, locally advanced, or metastatic urothelial carcinoma who had received one or two previous lines of treatment. They had an ECOG performance status of 0 or 1 and no prior PARP inhibitor therapy.
“Unfortunately in the ATLAS trial we did not see any confirmed responses,” said Grivas. Instead, 28.4% of patients had stable disease as their best response.
However, he added that “there was a number of patients who had modest activity, with [a] reduction in the tumor size.”
Petros Grivas explains why there is still hope for PARP inhibitors in advanced urothelial carcinoma despite the negative results of the ATLAS trial of rucaparib in this setting (4:45).
Efficacy did not significantly differ according to whether tumors were homologous recombination deficient (HRD). Twenty patients had HRD-positive tumors, 30 were negative, and 47 could not be determined. The researchers had hypothesized that HRD-negative tumors would respond better to PARP inhibition.
Median progression-free survival was short, at just 1.8 months, and again did not differ across the HRD subgroups.
Almost all patients had treatment-emergent adverse events, with the most common events of at least grade 3 being anemia (20.6%), thrombocytopenia (11.3%), and asthenia/fatigue (8.2%).
The investigators also took a closer look at mutations in four DNA damage response genes (BRCA1, BRCA2, RAD51C, and PALB2) thought to be associated with PARP inhibitor activity and found these to be relatively rare, affecting just 9.4% of patients. Alterations in TP53 and in FGF and its receptor were frequent, however, and the latter often occurred concurrently with CCND1 amplifications.
These observations are consistent with findings from the TCGA–BLCA dataset, Grivas noted.
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