Olaparib Monotherapy for <i>BRIP1</i>-Mutated High-Grade Serous Endometrial Cancer

Nakamura, Kazuto; Aimono, Eriko; Tanishima, Shigeki; Imai, Michiko; Nagatsuma, Akiko Kawano; Hayashi, Hideyuki; Yoshimura, Yuki; Nakayama, Kentaro; Kyo, Satoru; Nishihara, Hiroshi

doi:10.1200/po.19.00368

Cited by 16 publications

(14 citation statements)

References 19 publications

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“…In conclusion, we agree with Nakamura et al 1 that PARP inhibitors should be explored in patients with advanced endometrial carcinoma, beyond those with rare mutations in BRCA or related genes. The UTOLA trial will help to answer this question.…”

supporting

confidence: 91%

PARP Inhibitor in Advanced Endometrial Carcinoma BeyondBRCAand Related Genetic Mutations

Alexandre

Joly

2020

JCO Precision Oncology

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Nakamura et al 1 reported a durable clinical response to the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib in a patient with advanced high-grade serous endometrial carcinoma harboring a BRIP1 somatic mutation. The authors stated that there are currently no trials of PARP inhibitors in endometrial carcinoma, mainly because mutations in BRIP1, BRCA1, BRCA2, and other homologous recombination (HR)-related genes are too rare, being reported overall in , 5% of cases. 2

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supporting

confidence: 91%

PARP Inhibitor in Advanced Endometrial Carcinoma BeyondBRCAand Related Genetic Mutations

Alexandre

Joly

2020

JCO Precision Oncology

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“…The genomic test was performed prior to chemotherapy. Details of this patient's clinical sequence and therapy have already been reported in our previous case report [7]. Therefore, this case is briefly introduced in the present report.…”

Section: Casementioning

confidence: 82%

Clinical Outcomes of Genotype-Matched Therapy for Recurrent Gynecological Cancers: A Single Institutional Experience

et al. 2021

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Recent advances in next-generation sequencing and genome medicine have contributed to treatment decisions in patients with cancer. Most advanced gynecological cancers develop resistance to chemotherapy and have a poor prognosis. Therefore, we conducted genomic tests in gynecological tumors to examine the efficacy and clinical feasibility of genotype-matched therapy. Target sequencing was performed in 20 cases of gynecological cancers (cervical cancer, 6; endometrial cancer, 6; and ovarian cancer, 6). Both actionable and druggable genes were identified in 95% (19/20) of the cases. Among them, seven patients (35%) received genotype-matched therapy, which was effective in three patients. Of the three patients, one patient with a PTEN mutation received everolimus, another patient with a TSC2 mutation received everolimus and letrozole, and the patient with a BRIP1 mutation received olaparib. Subsequently, disease control in these three patients lasted for more than half a year. However, all patients relapsed between 9 and 13 months after the initiation of genotype-matched therapy. In this study, the response rate of genotype-matched therapy was 43% (3/7), which may have contributed to improved prognoses. Therefore, genotype-matched therapies may help patients with refractory gynecological cancers achieve better outcomes.

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“…Since PARP inhibitors are active and result in substantial improvements in prognosis, especially among HR deficient HGSOCs, HRD and the potential benefit from PARP inhibitors are of great interest also in SEC. This is underlined by the efficacy of the PARP inhibitor olaparib presented in a recent case report of SEC [ 34 ]. To date, HRD has been shown to occur in about 50% of all HGSOCs, and HRD is to a large extent due to mutations in the BRCA1 and BRCA2 genes and these mutations are frequently in the germline [ 12 , 13 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Homologous Recombination Repair Mechanisms in Serous Endometrial Cancer

Jönsson

Bååth

Björnheden

et al. 2021

Cancers

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Serous endometrial cancer (SEC) resembles high-grade serous ovarian cancer (HGSOC) genetically and clinically, with recurrent copy number alterations, TP53 mutations and a poor prognosis. Thus, SEC patients may benefit from targeted treatments used in HGSOC, e.g., PARP inhibitors. However, the preclinical and clinical knowledge about SEC is scarce, and the exact role of defective DNA repair in this tumor subgroup is largely unknown. We aimed to outline the prevalence of homologous recombination repair deficiency (HRD), copy-number alterations, and somatic mutations in SEC. OncoScan SNP arrays were applied to 19 tumors in a consecutive SEC series to calculate HRD scores and explore global copy-number profiles and genomic aberrations. Copy-number signatures were established and targeted sequencing of 27 HRD-associated genes was performed. All factors were examined in relation to HRD scores to investigate potential drivers of the HRD phenotype. Ten of the 19 SEC tumors (53%) had an HRD score > 42, considered to reflect an HRD phenotype. Higher HRD score was associated with loss of heterozygosity in key HRD genes, and copy-number signatures associated with non-BRCA1/2 dependent HRD in HGSOC. A high number of SECs display an HRD phenotype. It remains to be elucidated whether this also confers PARP inhibitor sensitivity.

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Olaparib Monotherapy for BRIP1-Mutated High-Grade Serous Endometrial Cancer

Cited by 16 publications

References 19 publications

PARP Inhibitor in Advanced Endometrial Carcinoma BeyondBRCAand Related Genetic Mutations

PARP Inhibitor in Advanced Endometrial Carcinoma BeyondBRCAand Related Genetic Mutations

Clinical Outcomes of Genotype-Matched Therapy for Recurrent Gynecological Cancers: A Single Institutional Experience

Homologous Recombination Repair Mechanisms in Serous Endometrial Cancer

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