Danielle Brazel*, Darren Sigal
Purpose: There is a strong rationale for targeting poly(ADPribose)
polymerase (PARP), which is responsible for repairing
single-stranded deoxyribonucleic acid (DNA) breaks, in tumors
with HRD including deficiencies in BRCA1/2 and associated
proteins. PARP inhibitors are FDA approved for use in ovarian,
breast, prostate, and pancreatic cancers with BRCA1/2 germline
mutations. HRD has been reported at low frequencies in a variety
of other malignancies and we sought to determine the efficacy of
olaparib in patients harboring these tumors.
Patients: We present three patients with BRCA1, BRCA2, and ATM
mutations in malignancies not generally associated with these
mutations who derived clinical benefit from olaparib monotherapy.
Patient 1 with BRCA1 mutated neuroendocrine tumor achieved
CR for 5 months before ultimately progressing. Patient 2 shows
stable disease nine months after starting olaparib monotherapy
for ATM mutated cholangiocarcinoma. Patient 3 was recently
started on olaparib for BRCA1 mutated gastric carcinoma and
has stable disease at his 6-month follow-up.
Conclusion: These cases demonstrate that olaparib can
confer clinical benefit across a broader range of HRR altered
malignancies, including those with somatic mutations.