In an analysis of a single-center trial reported in a research letter in JAMA Oncology, Reiss et al identified long-term outcomes with rucaparib maintenance in patients with platinum-sensitive advanced pancreatic ductal adenocarcinoma (PDAC) with BRCA1, BRCA2, or PALB2 germline or somatic pathogenic variants.
Study Details
In the trial, 42 patients enrolled between September 2017 and October 2019 at the Abramson Cancer Center, University of Pennsylvania, who had received at least 16 weeks of platinum-based chemotherapy without evidence of platinum resistance, and were treated with rucaparib at 600 mg twice-daily until progression or unacceptable toxicity. The primary endpoint was progression-free survival.
Key Findings
Among the 42 patients, 27 had germline BRCA2, 7 had germline BRCA1, 6 had germline PALB2, and 2 had somatic BRCA2 pathogenic variants. A total of 40 patients had metastatic disease.
Median follow-up was 77.9 months (range = 1.3–82.7 months), median progression-free survival was 12.8 months (range = 0.9–82.4 months), and median overall survival was 24.3 months (range = 1.3–82.4 months).
A total of seven patients (16.7%) designated as patients with long-term nonprogression (defined as progression-free survival > 5 years) remained alive and progression-free for more than 5.5 years, with a median progression-free survival of 74.7 months (range = 67.8–82.4 months). Among those seven patients, four were receiving rucaparib and in clinical remission at the time of data cutoff, whereas three discontinued rucaparib based on toxicity or personal preference (median time on rucaparib = 43.9 months, range = 37.5–58.1 months). One of the three patients who discontinued maintenance rucaparib developed local recurrence at 38 months after discontinuation of therapy, and the other two patients remained progression-free for 24.5 and 34.8 months after rucaparib discontinuation, respectively. Among the seven patients with long-term nonprogression, five had germline BRCA2, one had germline PALB2, and one had somatic BRCA2 pathogenic variants.
Fatal treatment-related myelodysplastic syndrome and acute myeloid leukemia developed in one patient each after 33.2 and 49.1 months of rucaparib treatment, respectively.
Among the seven patients with BRCA1 pathogenic variants, the median progression-free survival was 3.7 months (range = 1.5–9.1 months). Tissue samples were available for four patients, with samples from two showing retention of the wild-type allele.
The investigators concluded: “We report to date the longest follow-up data of patients with advanced PDAC receiving a maintenance PARP inhibitor after completion of induction chemotherapy…. More than 16% of the original trial cohort remained in clinical remission for more than 5 years receiving oral targeted therapy, and 3 patients remained progression-free without all treatment for several years. When contrasted with the 5-year survival rate of 3% in patients with metastatic PDAC, this observation is particularly notable. Given the observed 5% rate of myelodysplastic syndrome or acute myeloid leukemia, vigilance regarding late-onset cytopenias is warranted.”
Kim A. Reiss, MD, of Perelman Center For Advanced Medicine, Philadelphia, is the corresponding author for the JAMA Oncology article.
DISCLOSURE: The study was supported by Clovis Oncology and others. For full disclosures of the study authors, visit jamanetwork.com.
