Forty-month durable partial response with well-tolerated olaparib maintenance in a 92-year-old patient with BRCA2-mutated uterine serous carcinoma: a case report

Introduction

The incidence and mortality of endometrial cancer (EC) have been rising, a trend partly attributable to population aging (1). Older patients, particularly those with high-grade, aggressive histological subtypes such as uterine serous carcinoma (USC), often face significant treatment challenges due to comorbidities, frailty, and limited tolerance to therapy, leading to unfavorable oncologic outcomes. With the incorporation of molecular profiling into clinical practice, a subset of ECs has been recognized to exhibit homologous recombination deficiency (HRD), including tumors harboring BRCA mutations, providing a rationale for the use of poly(ADP-ribose) polymerase (PARP) inhibitors (2). Although PARP inhibitors are not currently approved for EC, emerging evidence from translational studies and individual clinical reports supports their potential role as maintenance therapy in selected patients with advanced-stage disease and HRD-associated biomarkers, including BRCA mutations. This report presents the case of a 92-year-old patient with International Federation of Gynecology and Obstetrics (FIGO) stage IVB USC and a somatic BRCA2 mutation, who achieved a durable partial response (PR) with olaparib maintenance therapy. This case highlights the feasibility and tolerability of PARP inhibitor-based maintenance in a highly vulnerable population and underscores the value of precision oncology in expanding therapeutic options for older patients with aggressive EC. We present this article in accordance with the CARE reporting checklist (available at https://gpm.amegroups.com/article/view/10.21037/gpm-2025-1-80/rc).

Case presentation

History of present illness

A 92-year-old female was admitted on May, 2022, with a one-month history of irregular vaginal bleeding. Gynecological examination revealed an ulcerated and necrotic cervix measuring slightly >2 cm in diameter, which bled on contact. The uterus was atrophic with limited mobility. A firm, ill-defined, non-tender mass approximately 5 cm in diameter was palpated in the left adnexal region with poor mobility. Contrast-enhanced computed tomography (CT), performed at an outside hospital in May 2022, revealed a cystic-solid mass in the left adnexal region, highly suspicious for malignancy, with suspected uterine involvement and extensive metastases to the peritoneum, retroperitoneal lymph nodes, bladder wall, and liver. A cervical biopsy identified a malignant neoplasm most consistent with high-grade serous adenocarcinoma. The serum cancer antigen 125 (CA-125) level was elevated at 588.9 U/mL. Her past medical history includes rectal cancer treated surgically in 2004 followed by four cycles of adjuvant chemotherapy, and long-standing hypertension well-controlled with bisoprolol 30 mg daily. Regarding gynecologic and reproductive history, she was gravida 4, para 3, and reached menopause at 50 years of age. She never smoked and did not consume alcohol. She reported strong social support, and no significant family history of malignancy was identified.

Surgery

Following a multidisciplinary team (MDT) discussion, the patient underwent an abdominal radical hysterectomy with bilateral salpingo-oophorectomy, omentectomy and bowel repair. Given her advanced age, extensive tumor burden, diffuse intraoperative bleeding, and hemodynamic instability with marked fluctuations in blood pressure and heart rate, systematic pelvic and para-aortic lymphadenectomy was omitted. Due to the extensive disease and perioperative instability, optimal cytoreduction was not feasible, and the procedure resulted in R2 cytoreduction (macroscopic residual disease). Postoperative histopathology confirmed high-grade USC with full-thickness myometrial invasion and lymphovascular space invasion. The carcinoma extensively involved the full thickness of the cervical mucosa and stroma, bilateral adnexa, the resection margins of both pelvic sidewalls, the greater omentum (Figure 1), and multiple peritoneal and small-bowel wall nodules. Ascitic fluid cytology was positive for adenocarcinoma cells. Accordingly, the patient was diagnosed with high-grade USC, FIGO stage IVB.

Figure 1 Comprehensive clinical timeline of the patient. The timeline summarizes the patient’s diagnosis, initial cytoreductive surgery, postoperative pathological findings confirming metastatic involvement of the greater omentum by uterine serous carcinoma consistent with FIGO stage IVB, chemotherapy, the olaparib maintenance therapy, serial radiologic assessments, longitudinal serum CA-125 levels, and TRAEs. Hematologic toxicities are illustrated by trends in white blood cell count and hemoglobin level. Staining method: hematoxylin and eosin; magnification: 40×. CA-125, cancer antigen-125; CT, computed tomography; FIGO, International Federation of Gynecology and Obstetrics; HGB, hemoglobin; PR, partial response; TRAEs, treatment-related adverse events; WBC, white blood cell.

Histopathological and molecular findings

Immunohistochemistry (IHC) showed CK7 positivity and CK20 negativity, with diffuse aberrant p53 expression, p16 overexpression, WT-1 positivity, and positive estrogen and progesterone receptor staining. Mismatch repair protein expression was retained (MLH1, PMS2, MSH2, MSH6), indicating mismatch repair (MMR) proficiency. Molecular profiling classified the tumor as the NSMP (no specific molecular profile) subtype and identified a somatic pathogenic BRCA2 mutation, accompanied by HRD score of 54. According to the performing laboratory report, the HRD score is derived from genomic scar components (LOH, TAI, and LST), and HRD positivity is defined as an HRD score ≥30.

Chemotherapy and maintenance therapy

Given the patient’s advanced age, surgery outcome, Eastern Cooperative Oncology Group (ECOG) performance status, and the anticipated limited tolerance to intensive combination chemotherapy, weekly single-agent carboplatin was initiated in July 2022. After 18 weeks of treatment, completed in October 2022, tumor assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 demonstrated a PR, with residual measurable disease confined to the pelvis and abdomen. In view of the disease characteristics, the presence of a somatic BRCA2 mutation, and a creatinine clearance of 48.54 mL/min (consistent with moderate renal impairment), maintenance therapy with olaparib was initiated using a proactive dose-attenuation approach. Considering both renal function–related exposure concerns and the patient’s extreme age with anticipated vulnerability to treatment-related adverse events (TRAEs), olaparib was started at 150 mg twice daily with close clinical and laboratory monitoring (Figure 1, comprehensive timeline).

Follow-up

At the time of manuscript revision (March, 2026), the patient has remained on olaparib maintenance at 150 mg twice daily for 40 months since late November 2022. On serial imaging, the longest diameter of the target mesenteric lesion decreased from 1.1 cm at baseline to 0.6 cm at the first evaluation and remained stable at 0.6 cm on the subsequent two assessments, consistent with a sustained PR (Figure 2). Serum CA-125 levels were monitored concurrently and remained consistently low and stable throughout follow-up. Routine surveillance, including serial complete blood counts, liver/kidney function tests and toxicity assessments, revealed that all TRAEs were Grade 1 or lower. The patient remains in good general condition to date and olaparib maintenance is ongoing because the patient achieved a durable PR rather than complete response. To provide an integrated overview of the patient’s longitudinal clinical course, a comprehensive timeline was completed in Figure 1, summarizing the diagnosis, cytoreductive surgery with postoperative pathological confirmation of FIGO stage IVB disease, chemotherapy, the olaparib maintenance period, serial CT assessments, serum CA-125 fluctuations and TRAEs.

Figure 2 Tumor radiographic response before and after initiation of olaparib maintenance therapy. (A) Peritoneal lesion (red arrow) in the paracolic gutter at baseline (November 2022). (B) The same peritoneal lesion (red arrow) in the paracolic gutter at follow-up (September 2025), showing regression. (C) Target mesenteric lesion (red arrow) at baseline (November 2022). (D) Follow-up imaging of the target mesenteric lesion (red arrow) (September 2025), demonstrating a decrease in size.

Ethical statement

All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

The incidence and mortality of EC are rising globally, a trend largely attributed to population aging. Epidemiologic studies indicate that women diagnosed with EC at an older age are more likely to present with high-grade disease, aggressive histologic subtypes, deep myometrial invasion, lower uterine segment involvement, and advanced stage disease (1,3). Older adults (age ≥65 years) also frequently have comorbidities that complicate cancer treatment. A primary concern is the increased prevalence of frailty, defined as a state of diminished physiological reserve, and a predisposition to adverse events (4). In EC, frailty is associated with age, with an incidence of 34% in patients aged ≥70 years, compared with an overall rate of 1.8% across all ages (5). We present the case of a 92-year-old patient with FIGO stage IVB high-grade USC who achieved sustained disease control, good tolerability, and an improved quality of life with olaparib maintenance therapy following sub-optimal cytoreductive surgery and weekly single-agent carboplatin.

While treatment decisions for older adults with cancer are often complicated by competing health conditions, molecularly targeted therapies such as PARP inhibitors may offer a promising approach for carefully selected patients. Although PARP inhibitors are not yet approved for EC, accumulating evidence from case reports and clinical studies supports their potential utility (6). The molecular rationale lies in synthetic lethality in tumors with HRD, in which impaired homologous recombination repair (HRR) renders tumor cells more dependent on PARP-mediated DNA damage repair. PARP inhibition therefore promotes the accumulation of unrepaired DNA damage and tumor cell death. A subset of ECs exhibits HRD, typically arising from pathogenic alterations in HRR genes such as BRCA1/2 and other HRR pathway components, and/or with genomic scar signatures captured by HRD assays (7-9). Forster et al. (10) reported a case of recurrent EC with PTEN loss in which treatment with Olaparib resulted in the shrinkage of brain metastases. Gockley et al. (11) described a patient with a germline BRCA2 mutation who maintained a response for 15 months on Olaparib maintenance therapy. The randomized phase IIb UTOLA trial evaluated single-agent maintenance olaparib versus placebo after first-line platinum-based chemotherapy in advanced/metastatic EC, with HRD status as a predictive biomarker for efficacy. In our case, a 92-year-old patient with a somatic pathogenic BRCA2 mutation and an HRD score of 54 (≥30, HRD-positive by the assay-defined cutoff), achieved a PR after postoperative chemotherapy and subsequently received olaparib maintenance with sustained remission for 40 months. This outcome supports the value of biomarker-driven PARP inhibitor maintenance in selected, extremely elderly population. Exploration of PARP inhibitors in the maintenance setting for EC is expanding, particularly in newly diagnosed advanced disease. Phase III trials DUO-E and RUBY Part 2 have evaluated the efficacy of PARP inhibitors combined with immune checkpoint inhibitors and chemotherapy, with available data suggesting the combination may enhance efficacy in mismatch repair proficient (pMMR) populations.

Despite the underrepresentation of older patients in clinical trials, evidence from ovarian cancer suggests that PARP inhibitors confer comparable efficacy in older and younger patients (12). The most common adverse events associated with PARP inhibitors include myelosuppression, fatigue, and gastrointestinal toxicities (13). While PARP inhibitors are generally tolerable in the elderly, their use in patients aged ≥75 years should ideally be informed by a comprehensive geriatric assessment to balance clinical benefit against toxicity risk and to guide individualized dose selection (12,14). In the present case, olaparib was initiated at a reduced dose (150 mg twice daily) rather than the standard 300 mg twice daily. This decision was multifactorial, informed by the patient’s moderate renal impairment and her advanced age with anticipated geriatric vulnerability; therefore, a proactive dose attenuation strategy was adopted to minimize the risk of TRAEs while maintaining treatment continuity. TRAEs were predominantly grade 1, with only mild hematologic adverse events that were manageable with supportive care. Further clinical trials and real-world studies in older populations are warranted to better define optimal dosing, monitoring strategies, and the role of geriatric assessment in maximizing the efficacy-safety profile of PARP inhibitor maintenance.

Several points should be considered when interpreting this case. As an observation from a single patient, the sustained PR and favorable tolerability seen with reduced-dose olaparib maintenance cannot be assumed to extend to a broader population of patients with USC. Olaparib was started at 150 mg twice daily in light of advanced age and moderate renal impairment, and treatment was continued at that dose without re-escalation. While this approach was clinically feasible in the present case, the optimal dose intensity for very elderly patients with USC remains undefined. Despite these limitations, the present case remains clinically informative as a carefully documented example of durable disease control with acceptable tolerability in a very elderly patient with BRCA2-mutated USC.

Conclusions

In summary, this case demonstrates that olaparib maintenance therapy may be a feasible, effective, and well-tolerated treatment option for very elderly patients with advanced BRCA-mutated USC. It also underscores the critical role of comprehensive molecular profiling in guiding precision medicine for EC, particularly in older patients who may have limited therapeutic options and reduced tolerance to conventional treatments. Incorporating genomic-guided decision-making can facilitate more appropriate individualized treatment strategies and may help to bridge existing treatment disparities through precision oncology.

Acknowledgments

We would like to express our sincere gratitude to this patient for allowing us to share her story.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://gpm.amegroups.com/article/view/10.21037/gpm-2025-1-80/rc

Peer Review File: Available at https://gpm.amegroups.com/article/view/10.21037/gpm-2025-1-80/prf

Funding: This research was supported by Natural Science Foundation of Sichuan Province (No. 2025ZNSFSC0541).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gpm.amegroups.com/article/view/10.21037/gpm-2025-1-80/coif). X.L. serves as an unpaid editorial board member of Gynecology and Pelvic Medicine from November 2025 to December 2026. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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