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Maintenance Rucaparib in Patients With Platinum-Sensitive Pancreatic Cancer and Germline or Somatic BRCA1, BRCA2, or PALB2 Variants


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In a single-institution phase II study reported in the Journal of Clinical Oncology, Kim A. Reiss, MD, and colleagues found that maintenance treatment with the poly (ADP-ribose) polymerase (PARP) inhibitor rucaparib produced responses and was associated with good progression-free survival in patients with platinum-sensitive advanced pancreatic cancer and germline or somatic pathogenic variants in BRCA1, BRCA2, or PALB2.

Kim A. Reiss, MD

Kim A. Reiss, MD

Study Details

Forty-two eligible patients were enrolled in the investigator-initiated trial between September 2017 and October 2019 at the Abramson Cancer Center at University of Pennsylvania. Patients had received at least 16 weeks of platinum-based chemotherapy without evidence of platinum resistance. Chemotherapy was discontinued and patients received rucaparib at 600 mg orally twice a day until disease progression or unacceptable toxicity.

Among the 42 patients, 27 had germline BRCA2, 7 had germline BRCA1, 6 had germline PALB2, and 2 had somatic BRCA2 pathogenic variants. Histology was adenocarcinoma in 40 patients, acinar in 1, and squamous cell carcinoma in 1. The primary endpoint was 6-month progression-free survival.

Progression-Free Survival and Responses

Among all patients, with a median potential progression-free survival follow-up of 18 months, progression-free survival was 59.5% (95% confidence interval [CI] = 44.6%–74.4%) at 6 months and 54.8% (95% CI = 39.7%–69.9%) at 12 months. Median progression-free survival was 13.1 months (95% CI = 4.4–21.8 months).

With a median potential overall survival follow-up of 24.0 months, median overall survival was 23.5 months (95% CI = 20.0–27.0 months). At data cutoff, eight patients remained alive and in active follow-up more than 2 years after starting therapy with rucaparib, with four remaining free of disease progression.

Among 36 patients with measurable disease, objective response was observed in 15 (41.7%, 95% CI = 25.5%–59.2%), including complete response in 3. The disease control rate was 66.7% (95% CI = 49.0%–81.4%). Median duration of response was 17.3 months (95% CI = 8.8–25.8 months). Responses were observed in 11 (40.7%) of 27 patients with germline BRCA2, 3 (50%) of 6 with germline PALB2, 1 (50%) of 2 with somatic BRCA2, and 0 (0%) of 7 with germline BRCA1. Response was observed in one patient with squamous cell carcinoma and germline PALB2.

KEY POINTS

  • Progression-free survival was 59.5% at 6 months and 54.8% at 12 months.
  • Responses were observed in patients with germline BRCA2 and PALB2 and somatic BRCA2 pathogenic variants.

Adverse Events

The most common treatment-related adverse events of any grade were anemia (74%), nausea (48%), increased alanine aminotransferase (ALT; 47%), fatigue (45%), thrombocytopenia (39%), and dysgeusia (37%). Treatment-related grade 3 adverse events (no grade 4 events observed) consisted of anemia (22%), fatigue (4%), increased ALT (4%), thrombocytopenia (4%), nausea (2%), vomiting (2%), and decreased white blood cell count (2%).

Treatment was discontinued due to a treatment-related adverse event in one patient (grade 3 fatigue). Adverse events led to dosage interruption in 33% of patients and dose reduction in 20%.

The investigators concluded, “Maintenance rucaparib is a safe and effective therapy for platinum-sensitive, advanced pancreatic cancer with a pathogenic variant in BRCA1, BRCA2, or PALB2. The finding of efficacy in patients with germline PALB2 and somatic BRCA2 pathogenic variants expands the population likely to benefit from PARP inhibitors beyond germline BRCA1/2 pathogenic variant carriers.”

Dr. Reiss, of the Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Clovis Oncology, Basser Center Young Leadership Council, Konner Fund, and others. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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