Effectiveness of Olaparib Treatment in a Patient with Gallbladder Cancer with an ATM-Inactivating Mutation

Abstract

Here, we report a case of postoperative recurrence of gallbladder carcinoma (GBC) in a patient who declined systemic chemotherapy. ATM S1905Ifs*25 and STK11 K262Sfs*25 mutations were detected by next-generation sequencing. Oral administration of olaparib was initiated. One month later, the patient experienced relief of clinical symptoms, a decrease in CA19-9 level, and a reduction in abnormal signal in the subcapsular region. The tumor response remained stable for approximately 13 months. This is the first case to demonstrate the clinical benefits of olaparib treatment in a patient with GBC harboring an ATM-inactivating mutation. This observation helps to better inform treatment options to enhance the care of patients with advanced GBC. The Oncologist 2020;25:375-379 KEY POINTS • A patient with gallbladder carcinoma harboring an ATM-inactivating mutation responded to olaparib with a progression-free survival of 13 months. • This is the first report that demonstrates the clinical benefits of olaparib treatment in a patient with gallbladder carcinoma with an ATM-inactivating mutation. • It also highlights the importance of next-generation sequencing, which can provide valuable information for planning effective targeted therapies for gallbladder carcinoma. • Evidence-based decisions help determine the best choice of treatment for individualized patient care.

In Silico Molecular Dynamics Docking of Drugs to the Inhibitory Active Site of SARS-CoV-2 Protease and Their Predicted Toxicology and ADME

“…Figure 4 shows the top 20 approved drugs, and the top 10 are described in detail as follows. Olaparib (Rank 35, BE=-8.7, B09074) is a PARP inhibitor primarily indicated for the treatment of ovarian cancer, but has been useful for pancreatic cancer, advanced solid tumors, and gallbladder cancer [87][88][89][90][91][92] . Etoposide (Rank 56, BE=-8.6, B00773) is for use in combination with other chemotherapeutic agents in the treatment of refractory testicular tumors and as first line treatment in patients with small cell lung cancer.…”

A Novel ATM Pathogenic Variant in an Italian Woman with Gallbladder Cancer

“…In particular, NGS results could be useful for such patients with no better treatment options in order to establish personalized treatment approaches. In fact, patients with homologous recombination deficiency (HRD) are considerably more likely to respond to drugs that impact DNA stability including platinum drugs and poly (ADP-ribose) polymerase (PARP) inhibitors [ 32 ], as recently reported by Zhang et al [ 33 ]. These authors described the first case showing the clinical benefits of olaparib treatment in a patient with GBC harboring an ATM -inactivating mutation found in combination with a STK11 frameshift variant.…”

“…These authors described the first case showing the clinical benefits of olaparib treatment in a patient with GBC harboring an ATM -inactivating mutation found in combination with a STK11 frameshift variant. In this case, NGS analysis was performed on the tumor and no information regarding the germline origin of the two variants was provided [ 33 ]. The woman had a progression-free survival (PFS) of approximately 13 months following treatment with olaparib [ 33 ].…”

Systemic treatment of advanced or recurrent biliary tract cancer

“…Although PARP inhibitors and inhibitors of ataxia-telangiectasia mutated (ATM), another DNA repair protein, are currently being evaluated in multiple clinical trials on BRCAmutated breast cancer, they need to be prospectively evaluated in patients with cholangiocarcinoma. Zhang et al (72) reported on the efficacy of olaparib in a patient with gallbladder cancer with an ATM-inactivating mutation. SD was achieved, and the patient survived for 16 months on olaparib.…”