Rucaparib maintenance appears safe and effective for patients with platinum-sensitive, advanced pancreatic cancer and BRCA1/2 or PALB2 variants, according to research published in the Journal of Clinical Oncology.
Researchers conducted a phase 2 trial (ClinicalTrials.gov Identifier: NCT03140670) of rucaparib maintenance in 46 patients with advanced pancreatic cancer who had germline or somatic pathogenic variants in BRCA1, BRCA2, or PALB2.
The patients had received at least 16 weeks of platinum-based chemotherapy without any evidence of platinum resistance. After chemotherapy was stopped, patients received oral rucaparib (600 mg) twice a day until disease progression or unacceptable toxicity.
Of the 42 patients evaluable for efficacy, 27 had germline BRCA2, 7 had germline BRCA1, 6 had germline PALB2, and 2 had somatic BRCA2 variants.
At a median follow-up of 18 months, the median progression-free survival (PFS) was 13.1 months. The PFS at 6 months was 59.5%, and the PFS at 12 months was 54.8%. The median overall survival was 23.5 months.
There were 36 patients with measurable disease who were evaluable for response. The overall response rate (ORR) was 41.7%, which included 3 complete responses and 12 partial responses. The median duration of response was 17.3 months, and the disease control rate was 66.7%.
Rucaparib was active in patients with germline BRCA2, germline PALB2, and somatic BRCA2 variants. The ORR was 40.7% (11/27) for patients with germline BRCA2, 50% (3/6) for those with germline PALB2, 50% (1/2) for patients with somatic BRCA2, and 0% (0/7) for those with germline BRCA1 variants.
Treatment-related grade 3 adverse events (AEs) included anemia (22%), fatigue (4%), increased alanine aminotransferase (4%), thrombocytopenia (4%), nausea (2%), vomiting (2%), and reduced white blood cell count (2%).
There were no grade 4 treatment-related AEs. There was 1 serious treatment-related AE (hepatic dysfunction).
Based on these results, the researchers concluded that maintenance rucaparib is “a safe and effective therapy” for patients with platinum-sensitive, advanced pancreatic cancer with a pathogenic variant in BRCA1/2 or PALB2.
The researchers noted that rucaparib’s activity in patients with germline PALB2 and somatic BRCA2 variants suggests the role of PARP inhibition “might be expanded in clinical practice.”
Disclosures: This research was partly supported by Clovis Oncology. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reiss KA, Mick R, O’Hara MH, et al. Phase II study of maintenance rucaparib in patients with platinum-sensitive advanced pancreatic cancer and a pathogenic germline or somatic variant in BRCA1, BRCA2, or PALB2. J Clin Oncol. 2021;39(22):2497-2505. doi:10.1200/JCO.21.00003