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Rucaparib maintenance therapy may benefit certain patients with advanced pancreatic cancer
ATLANTA — Patients with advanced BRCA- or PALB2-mutated pancreatic cancer sensitive to platinum-based chemotherapy demonstrated sustained clinical responses to maintenance treatment with rucaparib, according interim data from an ongoing phase 2 trial presented at American Association for Cancer Research Annual Meeting.
Rucaparib (Rubraca, Clovis Oncology), a poly(ADP-ribose) polymerase (PARP) inhibitor, also appeared well-tolerated among this patient subgroup.
“Patients with BRCA or PALB2 mutations in pancreatic cancer have an exceptional response to platinum chemotherapy, as you might imagine, given their biology,” Kim Reiss Binder, MD, assistant professor of medicine in the division of hematology and oncology at the Hospital of the University of Pennsylvania, and a HemOnc Today Next Gen Innovator, said during a press conference. “They do very, very well; they can be on chemotherapy for months, sometimes years, and the only thing we can do in the advanced-disease setting as standard of care is continuous, indefinite chemotherapy.
“So, toxicity builds and the quality of life of our patients goes down,” Reiss Binder added. “But what about a new model? What about using chemotherapy as an induction, to bring everything down, cool things off, and find a lower-toxicity maintenance strategy?”
Reiss Binder and colleagues plan to enroll 42 participants in the single-arm, phase 2 trial, which is open to patients with advanced pancreatic cancer and a pathogenic germline or somatic BRCA or PALB2 mutation who have undergone at least 4 months of platinum-based chemotherapy without disease progression. Patients with a medical contraindication to the full 4-month regimen of platinum are permitted at the lead investigator’s discretion.
The unplanned interim analysis included 19 patients (median age, 61 years; range, 35-81; 84% women) evaluable for PFS. These patients had germline BRCA1 (n = 13), germline BRCA2 (n = 3), germline PALB2 (n = 2) and somatic BRCA2 (n = 1) mutations.
Patients received a median 4 months (range, 0.5-32) of previous platinum-based chemotherapy for advanced disease.
Toxicity or allergic reaction prevented four of the 19 patients from completing a full 4 months of platinum chemotherapy. Two of the 19 patients had no measurable disease at the time of enrollment.
Trial participants received 300 mg oral rucaparib twice daily until disease progression or intolerable toxicity.
PFS served as the primary endpoint. Researchers also evaluated overall response rate.
With a median potential follow-up of 257 days, results showed median PFS of 9.1 months from the initiation of rucaparib.
Reiss Binder reported an ORR of 36.8%, including six partial responses and one complete response. Responders include four patients with germline BRCA2 mutations, two patients with germline PALB2 mutations and one patient with a somatic BRCA2 mutation.
The rate of disease control (complete response plus partial response plus stable disease) was 89.5% for a minimum of 8 weeks.
At the initial follow-up scan 2 months after starting treatment, two patients (10.5%) showed disease progression.
As of the interim analysis, eight patients were on rucaparib for more than 6 months (13 months) and two patients were on treatment beyond a year (15 months).
Researchers observed no dose-limiting toxicities associated with rucaparib. The most prevalent adverse events included nausea (grade 1, 46%; grade 2, 4.2%), dysgeusia (grade 1; 33.3%) and fatigue (grade 1; 25%). Nausea required dose reduction in one patient.
Reiss Binder described the sustained responses observed among patients in the interim analysis as “very exciting.”
“We are proposing a novel strategy to treat these patients for whom the standard of care is indefinite chemotherapy until progression, clinical decline or death,” she said. “This is very preliminary data, but it looks promising, at least in this group of patients, that this might be a strategy that we can study and pursue.” – by Jennifer Byrne
Reference:
Reiss Binder K, et al. Abstract CT234. Presented at: AACR Annual Meeting; March 29-April 3, 2019; Atlanta.
Disclosures: The study is sponsored by Abramson Cancer Center and funded by Clovis Oncology. Reiss Binder reports research funding from Bristol-Myers Squibb, Clovis Oncology, Lilly Oncology and Tesaro. Please see the abstract for all other authors’ relevant financial disclosures.