scholarly journals Assessing Frequency and Clinical Outcomes of BRCA Mutated Ovarian Cancer in Saudi Women

2020 ◽  
Author(s):  
Naela Agha ◽  
Bader Alshamsan ◽  
Sharifa Al-Farsi ◽  
Heba Aly Ateya ◽  
Fahed A Almugbel ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Outcomes ◽  
Brca1 Mutation ◽  
Objective Response ◽  
Disease Free Survival ◽  
Serous Carcinoma ◽  
Free Access ◽  
First Line ◽  
Brca Mutations ◽  
Saudi Women

Abstract Background: BRCA gene mutations (BRCAm) had an impact on patients' characteristics and clinical outcomes of ovarian cancer (OC). The frequency and patterns of BRCAm vary among countries and ethnicities. There are limited data from Saudi Arabia (SA); thus, this study aims to determine the frequency, pattern, and impact on patient characteristics and outcomes of BRCAm OC compared to wild-type BRCA (BRCAw) in Saudi women.This retrospective study evaluated women diagnosed with non-mucinous OC, fallopian tube, or peritoneal carcinoma who had BRCA status tested in an accredited lab between January 2016 and December 2017. The associations between various parameters and BRCAm were estimated using logistic regression. The objective response rate (ORR) of the first line and subsequent lines for BRCAm and BRCAw were evaluated using Response Evaluation Criteria in Solid Tumors Version 1. The disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan–Meier methods and compared by log-rank tests.Result: Sixty-one women with a median age of 52 at diagnosis were analyzed. Germline BRCA mutations were found in 41% of cases (25/61). The majority were BRCA 1 (92%), and the most common deleterious germline BRCA1 mutation was c.1140dupG (39%), followed by c.5530del (13%) and c.5095C>T (8%). Most women (72%) had no family history of cancers, all had high-grade serous carcinoma, and 82% had advanced stage at presentation. Regardless of BRCA mutations, an optimal ORR to first-line treatment has been achieved although most cases relapsed after the first line of management (84%) and the majority were platinum-sensitive relapse (85%). The ORR was higher in BRCAm in subsequent lines compared to BRCAw type. BRCAm women experienced longer median DFS (25 vs 17 months, p = 0.02) and a higher five-year OS rate (90.9% vs 66.7%, p = 0.19) than BRCAw.Conclusion: The prevalence of BRCAm of OC was higher in Saudi women when compared with the regional and most of the international figures. The better clinical outcomes of BRCAm women is in concordance with the reported evidence. Further studies on BRCA mutations of OC, education, genetic counseling, and free access to genetic testing are highly recommended.

scholarly journals Assessing Frequency and Clinical Outcomes of BRCA Mutated Ovarian Cancer in Saudi Women

2021 ◽  
Author(s):  
Naela Agha ◽  
Bader Alshamsan ◽  
Sharifa Al-Farsi ◽  
Heba Aly Ateya ◽  
Fahed A Almugbel ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Saudi Arabia ◽  
Clinical Outcomes ◽  
Brca Mutation ◽  
Brca1 Mutation ◽  
Research Center ◽  
Brca Mutations ◽  
Frequency Pattern ◽  
Saudi Women ◽  
King Faisal Specialist Hospital

Abstract Purpose: BRCA gene mutations (BRCAm) had an impact on patients' characteristics and clinical outcomes of ovarian cancer (OC). The frequency and patterns of BRCAm vary among countries and ethnicities. There are limited data from Saudi Arabia (SA); thus, this study aims to determine the frequency, pattern, and impact on patient characteristics and outcomes of BRCAm OC compared to wild-type BRCA (BRCAw) in Saudi women.Methods: This retrospective study evaluated women diagnosed with non-mucinous OC, fallopian tube, or peritoneal carcinoma who had BRCA status tested in an accredited lab between January 2016 and December 2017. The associations between various parameters and BRCAm were estimated using logistic regression. Statistical analysis performed with SPSS (Version 27). Result: Sixty-one women with a median age of 52 at diagnosis were analyzed. Germline BRCA mutations were found in 41% of cases (25/61). The most common deleterious germline BRCA1 mutation was c.1140dupG (39%). Most women (72%) had no family history of cancers and 82% had advanced stage. Regardless of BRCA mutations, an optimal overall response rate (ORR) to first-line treatment has been achieved although most cases relapsed (84%) and the majority were platinum-sensitive relapse (85%). Higher ORR to subsequent lines and better survival were obtained in women with BRCA-mutation.Conclusion: The prevalence of BRCAm of OC was higher in Saudi women compared to regional and most of the international figures. The better clinical outcomes of BRCAm women agreed with the reported evidence. Further studies on BRCA mutations of OC and genetic counseling are highly recommended.Trial registration number and The addresses of the institution at which the work was performed:Trial approved by the Institutional Review Board of King Faisal Specialist Hospital and Research Center (RAC # 2171137) and conducted at King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh 11211, Saudi Arabia.

scholarly journals Tumour Versus Germline BRCA Testing in Ovarian Cancer: A Single-Site Institution Experience in the United Kingdom

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 547
Author(s):  
Iolia Akaev ◽  
Siavash Rahimi ◽  
Olubukola Onifade ◽  
Francis John Edward Gardner ◽  
David Castells-Rufas ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Unknown Origin ◽  
Parp Inhibitors ◽  
Serous Carcinoma ◽  
High Grade ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Epithelial Cancers ◽  
Pathogenic Variants ◽  
Pathogenic Mutations

The aim of this audit was to evaluate the usefulness and serviceability of testing for pathogenic mutations in BRCA1 or BRCA2 (BRCA1/2) genes in ovarian cancer (OC) patients. One hundred and thirty-five patients with more common histological sub-types of OC were retrospectively identified between 2011 and 2019. The fail rate of the molecular analysis was 7.4% (10/135). One hundred and twenty-five records were evaluated: 99 (79.2%) patients had wild-type BRCA (both somatic and germline); tumour BRCA1/2 (tBRCA1/2) pathogenic mutations were found in 20 (16%) patients with distribution between BRCA1 and BRCA2 being 40% and 60%, respectively; 13 (10.4%) patients with pathogenic variants had germline mutations; and tBRCA1/2 with variant of unknown significance (VUS), in the absence of pathogenic BRCA1 or BRCA2 variants, was detected in 6 (4.8%) patients. Our data show that expanding the molecular service to the routine first-tumour testing for patients with OC will potentially increase the detection rate of BRCA mutations, thereby providing early benefits of PARP inhibitors therapy. The tumour testing service should continue to be offered to newly diagnosed patients with high-grade epithelial cancers, including high-grade serous carcinoma, but also with carcinosarcomas and poorly-differentiated metastatic adenocarcinomas of unknown origin.

Clinical outcomes and cost associated with HRD biomarker guided first line maintenance therapy in advanced ovarian cancer

2021 ◽  
Vol 162 ◽  
pp. S111-S112
Author(s):  
Daniel Simmons ◽  
Jigna Bhalla ◽  
Rebecca Stone ◽  
Julia Engstrom-Melnyk ◽  
Kimmie McLaurin
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Clinical Outcomes ◽  
Advanced Ovarian Cancer ◽  
First Line

scholarly journals Real-World Experience of Olaparib Maintenance in High-Grade Serous Recurrent Ovarian Cancer Patients with BRCA1/2 Mutation: A Korean Multicenter Study

2019 ◽  
Vol 8 (11) ◽  
pp. 1920 ◽  
Author(s):  
Paik ◽  
Lee ◽  
Lee ◽  
Shin ◽  
Park ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Real World ◽  
Partial Remission ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
High Grade ◽  
Platinum Sensitive

Background: Olaparib maintenance therapy has shown efficacy and tolerability in patients with platinum-sensitive, high-grade serous recurrent ovarian cancer (HSROC) with BRCA1/2 mutation (BRCAm). Our aim was to present real-world experience with olaparib in Korea. Method: We included HSROC patients with BRCAm treated with olaparib maintenance at four institutions in Korea between 2016 and 2018. Medical records were reviewed for clinico-pathologic characteristics, objective response, survival outcomes, and safety. Results: One hundred HSROC patients with BRCAm were included. BRCA1 mutation was present in 71 patients (71.0%), and BRCA2 mutation was present in 23 patients (23.0%). In terms of the best objective response with olaparib maintenance in 53 patients with partial remission from most recent chemotherapy, complete remission occurred in 12 (22.6%) and partial remission in four (7.5%), while 33 patients (62.3%) had stable disease. The 24 month progression-free survival was 42.4%, and 24 month overall survival was 82.1%. Grade 3 or more adverse events were as follows: anemia in 14 patients (14.0%), neutropenia in seven patients (7.0%), thrombocytopenia in two patients (2.0%), oral mucositis in one patient (1.0%), and soft tissue infection in one patient (1.0%). Conclusions: The safety and effectiveness of olaparib maintenance treatment in a real-world study were consistent with those reported in previous clinical trials.

scholarly journals Treatment Experience and Predictive Factors Associated with Response in Platinum-Resistant Recurrent Ovarian Cancer: A Retrospective Single-Institution Study

2021 ◽  
Vol 10 (16) ◽  
pp. 3596
Author(s):  
Radu Dragomir ◽  
Ioan Sas ◽  
Sorin Săftescu ◽  
Dorel Popovici ◽  
Roxana Margan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Predictive Factors ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Recurrent Ovarian Cancer ◽  
Serous Carcinoma ◽  
First Line ◽  
Chemotherapy Drugs ◽  
Platinum Resistant ◽  
Incidence And Mortality

Ovarian cancer (OC) represents the most common and lethal gynecologic malignancy, due to its increased incidence and mortality rate. It is usually diagnosed in advanced stages and, even though surgery and platinum-based treatments are initially efficient, recurrences emerge in over 70% of cases. Although there are multiple options of chemotherapy drugs from which to choose, little is known regarding the best strategy for prolonged survival. Thus, this study aimed to assess the effect that most frequently used chemotherapeutic regimens have upon time-to-treatment-failure (TTF) from the first line and beyond, considering clinical and biological factors which influence the treatment outcome of platinum-resistant recurrent OC. We retrospectively analyzed data from 78 patients diagnosed with platinum-resistant OC, who underwent chemotherapy-based treatment with or without anti-angiogenic therapy at OncoHelp Oncology Center, Romania (January 2016–February 2021). Our study identified positive predictive factors for TTF related to histology (serous carcinoma subtype), anthropometry (age over 60 for patients treated with topotecan with or without bevacizumab), renal function (creatinine levels between 0.65 and 1 mg/dL for patients treated with regimens containing bevacizumab and pegylated liposomal doxorubicin) and treatment choice (bevacizumab in combination with pegylated liposomal doxorubicin or topotecan used from the first line and beyond).

scholarly journals Assessing frequency and clinical outcomes of BRCA mutated ovarian cancer in Saudi women

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Naela Agha ◽  
Bader Alshamsan ◽  
Sharifa Al-Farsi ◽  
Heba Aly Ateya ◽  
Fahad A. Almugbel ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Saudi Arabia ◽  
Clinical Outcomes ◽  
Gene Mutations ◽  
Patient Characteristics ◽  
Research Center ◽  
Frequency Pattern ◽  
Saudi Women ◽  
Platinum Sensitive ◽  
King Faisal Specialist Hospital

Abstract Purpose BRCA gene mutations (BRCAm) have an impact on patients’ characteristics and clinical outcomes of ovarian cancer (OC). The frequency and patterns of BRCAm vary among countries and ethnicities. There are limited data from Saudi Arabia (SA); thus, this study aims to determine the frequency, pattern, and impact on patient characteristics and outcomes of BRCAm OC compared to wild-type BRCA (BRCAw) in Saudi women. Methods This retrospective study evaluated women diagnosed with non-mucinous OC, fallopian tube, or peritoneal carcinoma who had BRCA status tested in an accredited lab between January 2016 and December 2017. The associations between various parameters and BRCAm were estimated using logistic regression. Statistical analysis performed with SPSS (Version 27). Result Sixty-one women with a median age of 52 at diagnosis were analyzed. Germline BRCA mutations were found in 41% of cases (25/61). The most common deleterious germline BRCA1 mutation was c.1140dupG (39%). Most women (72%) had no family history of cancers and 82% had advanced stage. Regardless of BRCA mutations, an optimal overall response rate (ORR) to first-line treatment has been achieved although most cases relapsed (84%) and the majority were platinum-sensitive relapse (85%). Higher ORR to subsequent lines and better survival were obtained in women with BRCA-mutation. Conclusion The prevalence of BRCAm of OC was higher in Saudi women compared to regional and most of the international figures. The better clinical outcomes of BRCAm women agreed with the reported evidence. Further studies on BRCA mutations of OC and genetic counseling are highly recommended. Trial registration Trial approved by the Institutional Review Board of King Faisal Specialist Hospital and Research Center (RAC # 2171137) and conducted at King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh 11,211, Saudi Arabia.

Weekly association of gemcitabine and topotecan in early recurrent ovarian cancer patients: A French multicenter phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16016-16016
Author(s):  
F. Joly ◽  
T. Petit ◽  
P. Pautier ◽  
E. Guardiola ◽  
F. Mayer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Survival Time ◽  
Phase Ii ◽  
Stable Disease ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Recurrent Ovarian Cancer ◽  
First Line ◽  
Multicenter Phase

16016 Background: A weekly association of gemcitabine and topotecan was tested with the aim of evaluating its efficacy and tolerance in patients recurring after first line platinum and taxane-based chemotherapy. Methods: From December 2004 to April 2006, 77 patients whose disease has progressed within 12 months (time-free interval, TFI) after first line chemotherapy were enrolled in a multicenter phase II study. Primary endpoint was overall response rate (ORR). Gemcitabine (1000 mg/m2) and topotecan (2.5 mg/m2) were given day 1, 8 and 15 (q 28 d) for 6 to 9 cycles. Tumor response was assessed according to RECIST or Rustin criteria. Clinical response was assessed using symptoms improvement in responders and patients with stable disease. Follow-up was updated December 2006. Results: Initial characteristics were: median age 63 years (38 to 80), WHO PS 0–1 93%, serous histology 85%, TFI < 6 months 45%, measurable disease 71%. Four cycles (1 to 8) were administered in average. The only major toxicity was neutropenia (Grade 3 and 4 in 17% and 6% of patients) with one febrile neutropenia; one toxic death (pneumopathy) was observed. 34% of cycles were incomplete (d8 and/or d15 not administered) because of grade 1–2 thrombopenia or grade 1–4 neutropenia. Lenograstim and erythropoietin were administered in 14% and 34% of patients, respectively. Sixty-six (86%) patients were evaluable for response (2 cycles administered). The ORR was 14% (CR=3%, PR=11%); there were 53% of stable disease. ORR was 7% and 20% in patients with TFI < 6 months and = 6 months, respectively. Symptoms were improved in 18 (64%) of 28 patients and pain in 11 (39%) of 28 patients. Median event-free survival time was 3.7 months. Median overall survival time was 12.3 months (7.5 and 15.6 months in patients with TFI < 6 months and = 6 months, respectively; p=0.0244). Conclusions: In resistant/refractory ovarian cancer, weekly gemcitabine and topotecan is associated with low objective response rate but with a high proportion of stable disease and symptoms control leading to acceptable quality of life. No significant financial relationships to disclose.

Sequencing radium 223 (RA223) for metastatic castration-resistant prostate cancer (mCRPC) patients (pts) in the daily practice: Preliminary results from a retrospective study in Italian centers.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 322-322 ◽  
Author(s):  
Orazio Caffo ◽  
Viviana Frantellizzi ◽  
Luca Galli ◽  
Fabio Monari ◽  
Gaetano Facchini ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Objective Response ◽  
Daily Practice ◽  
Cross Resistance ◽  
Consecutive Series ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Radiation Mechanism ◽  
Castration Resistant ◽  
Radium 223

322 Background: The potential advantage of the sequential use of the active drugs (ADs) able to prolong overall survival (OS) in mCRPC (abiraterone, cabazitaxel, docetaxel, enzalutamide, RA223) could be limited by the development of common mechanisms of resistance. According to its unique targeted alpha-radiation mechanism of action, it could be postulated that RA223 does not induce and is not affected by cross-resistance with other agents and consequently its incorporation in therapeutic sequences may improve clinical outcomes. The present study is aimed to describe the clinical outcomes of pts who received RA223 and at least two other ADs for mCRPC. Methods: We collected data of pts who received sequentially 3 or more ADs of which one was RA223. For each pt we recorded the clinical outcome of all treatments received for mCRPC. We also compared the cumulative survival from the start of the first line to that of a contemporary series of 405 mCRPC pts without visceral mets sequentially treated with 3 or 4 ADs not comprising RA223. Results: A consecutive series of 119 mCRPC pts was collected: the median age was 72 yrs. Six pts received all 5 available ADs, 53 pts 4 ADs, and the remaining pts 3 ADs. Most of the pts received RA223 as the 3rd or 4th line of treatment (62 and 42, respectively), and the remaining were treated in less or more advanced lines (10 and 5 pts respectively). Overall the full 6-cycle treatment was completed in 61 pts (51.3%) and in 61.3% and 38.1% of pts when Ra223 was administered as 3rd and 4th treatment line respectively (p = 0.02). Partial response and stable disease as best objective response to RA223 was achieved in 11.3% and 24.5% of pts respectively, while a PSA reduction of ≥ 50% was observed in 7.2% of pts. Median OS from the start of the first line was 48 mos. In pts treated with 3 or 4 ADs that included Ra223, the median OS was significantly longer compared to that of pts whose treatment sequence did not include RA223 (48.4 vs 39.2 mos, p = 0.03). Conclusions: Despite the limitations of its retrospective nature, this preliminary data suggests that treatment sequencing of ADs that includes RA223 offers a survival advantage in mCRPC.

Clinicopathological features of patients with ovarian and breast cancer with BRCA mutation.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13524-e13524
Author(s):  
Metin Ozkan ◽  
Sedat Tarık Fırat ◽  
Ramazan Coşar ◽  
Oktay Bozkurt ◽  
Mevlude Inanc ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Germ Cell ◽  
Triple Negative ◽  
Brca Mutation ◽  
Brca1 Mutation ◽  
Germ Cell Tumors ◽  
Serous Carcinoma ◽  
Breast And Ovarian Cancer ◽  
Stage 4

e13524 Background: Breast cancer is the most common cancer and the leading cause of cancer death in women. Ovarian cancer contributes significantly to mortality and morbidity rates. BRCA1 and BRCA2 are the best known genes associated with breast and ovarian cancer, which are important in DNA repair and transcriptional regulation. Methods: In this study, we retrospectively analyzed the clinicopathological features of breast and ovarian cancer patients who were found to have BRCA 1/2 mutations in Erciyes University Medical Oncology between 2009-2019. Results: BRCA mutation was detected in 14 patients with breast cancer and 10 patients with ovarian cancer. The median age of patients with breast cancer was 41 (25-67). Of 14 BRCA mutated patients, 9 (64 %) patients had BRCA2 mutations while 5 (36 %) patients had BRCA1 mutations. All patients had invasive ductal carcinoma. Of 14 patients, 7 patients were grade 3, 6 patients were grade 2, 1 patient was grade 1. At the time of diagnosis, 5 of 14 patients were stage 3 and 5 patients were stage 4. 4 (80%) of 5 patients with stage 4 had BRCA 2 mutation. 5 of 10 patients who received adjuvant therapy after surgery had 4 or more lymph node metastases. Hormone receptor positive / HER2 negative disease was the most common molecular subgroup (8/14, 57%). Five patients were triple negative histology. 4 (80%) of triple negative patients had BRCA1 mutation. Ovarian cancer developed in 2 of 14 patients who had breast cancer with BRCA mutation. Median age of patients with ovarian cancer with BRCA mutation was 52.5 (19-67). 2 of 10 patients with ovarian cancer had germ cell tumors and 8 had epithelial serous carcinoma. Of 10 BRCA mutated patients, 7 (70 %) patients had BRCA2 mutations while 3 (30 %) patients had BRCA1 mutations. Both patients with germ cell tumors were stage 1 at the time of diagnosis, 7 of the patients with epithelial serous carcinoma were stage 3, and 1 was stage 2. While patients with germ cell tumors were followed without recurrence, 6 patients with epithelial serous carcinoma developed recurrence, and all of these patients were platinum sensitive. Breast cancer developed in 1 patient with BRCA1 mutation at follow-up. All patients were alive according to the last control date. Median DFS was 29 months. Conclusions: BRCA-related breast cancer is characterized by a more aggressive phenotype than sporadic breast cancer, BRCA1-associated breast cancer is more frequently high-grade and triple negative histology. BRCA-related ovarian cancer is more sensitive to treatment, especially platinum-based chemotherapy, and is associated with improved prognosis.

Combination of PARP and ATR inhibitors (olaparib and ceralasertib) shows clinical activity in acquired PARP inhibitor-resistant recurrent ovarian cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5516-5516
Author(s):  
Stephanie L. Wethington ◽  
Payal D Shah ◽  
Lainie P. Martin ◽  
Janos Laszlo Tanyi ◽  
Nawar A. Latif ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Kinase Inhibitors ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Clinical Trial Design ◽  
Recurrent Ovarian Cancer ◽  
Ca 125 ◽  
Clinical Activity ◽  
Brca Mutations

5516 Background: Following multiple blockbuster studies demonstrating long-term progression free and overall survival benefits with poly(ADP-ribose)polymerase inhibitors (PARPi), they have become an integral component of high grade serous ovarian cancer (HGSOC) treatment. Unfortunately, tumors ultimately acquire resistance and thus therapies that overcome PARPi-resistance are urgently needed. Preclinical studies show the addition of ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) to PARPi overcome PARPi-resistance. We present results of an investigator-initiated study of the combination PARPi (olaparib) and ATRi (ceralasertib) in patients who were on a PARPi and experienced disease progression. Methods: We conducted a non-randomized trial (NCT03462342) in platinum sensitive HGSOC immediately following prior PARPi treatment of a 28 day cycle of olaparib 300mg orally twice daily and ceralasertib 160mg orally once daily on days 1-7. Eligibility required a germline or somatic BRCA1/2 mutation, other homologous recombination deficient (HRD) mutation, or positive HRD score (>42 on Myriad My Choice). Clinical benefit from prior PARPi was required ( > 12 months on treatment for 1st line maintenance, > 6 months for ≥2nd line maintenance, or treatment of recurrence with response by CA-125 or imaging). No intervening treatment between the PARPi and enrollment was permitted. The primary objectives were safety and objective response rate (ORR). Results: Thirteen patients (pt) of median age 60 years (range 43-78) were enrolled. 9 pt (69%) had germline BRCA mutations, 3 (23%) somatic BRCA mutations and 1 (8%) a positive HRD score. Median time on prior PARPi was 13 months (range 4-60). Prior PARPi indication was 1st line maintenance in 8% (n = 1), 2nd line maintenance in 38% (n = 5) and recurrence in 54% (n = 7). Nine pt (69%) had received olaparib prior to enrollment. The time from prior PARPi to cycle 1, day 1 was 34 days (range 22-311). The ORR was 46% (n = 6); all 6 demonstrating a PR. Pt received a median of 8 (range 3-23) cycles of olaparib and ceralasertib. 4 pt remain on study (4-14 months). 4 pt (31%) experienced grade 3 toxicity: 23% (n = 3) thrombocytopenia, 16% (n = 2) anemia, and 16% (n = 2) neutropenia. There were no grade 4/5 toxicities. There were 4 dose reductions (3 olaparib, 1 ceralasertib). No pt discontinued treatment due to toxicity. Conclusions: The combination of olaparib and ceralasertib is well tolerated and shows clinical activity in in a cohort of patients with recurrent HRD HGSOC who have progressed on prior PARPi thus warranting further investigation. This study is the first to suggest the potential of ATR inhibitors to overcome PARPi resistance in an HRD patient population. Molecular profiling studies are underway to identify potential biomarkers associated with response to guide future clinical trial design. Clinical trial information: NCT03462342.

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