Abstract CT339: Prospective molecular identification of ovarian cancer patients benefiting from PARP inhibitor (PARPi, rucaparib) maintenance therapy - reaching beyond germline BRCA mutations

Author(s):  
Elizabeth Swisher ◽  
Iain McNeish ◽  
Robert L. Coleman ◽  
James D. Brenton ◽  
Scott H. Kaufmann ◽  
...  
2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 5558-5558
Author(s):  
Sana Intidhar Labidi-Galy ◽  
Thibault De La Motte Rouge ◽  
Olfa Derbel ◽  
Elsa Kalbacher ◽  
Anita Wolfer ◽  
...  

2020 ◽  
Vol 28 (3) ◽  
pp. 257-266
Author(s):  
Andrei Chicos ◽  
Lucian Negura ◽  
Rares Braescu ◽  
Aliona Morariu ◽  
Anca Negura ◽  
...  

AbstractHereditary predisposition to breast and ovarian cancer (HBOC) is diagnosed by molecular analysis of deleterious mutations in BRCA genes, allowing oncogenetic follow-up of patients and of their families. BRCA testing addresses only to HBOC families, using restrictive inclusion criteria based on familial history of cancer and age at diagnosis. Sporadic ovarian cancer has high incidence and mortality in Romania, with low median age of diagnosis and possibly a higher magnitude of hereditary contribution comparing to othe populations. However, sporadic ovarian cancers do not qualify for BRCA testing according to inclusion criteria, and a complete BRCA screening of all cancers is neither feasible nor recommended. Despite the large diversity of BRCA mutations worldwide, some recurrent mutations have higher frequencies in diverse populations. Precisely screening for recurrent mutations in a target population allows to rapidly identifying mutation carriers without sequencing the entire BRCA genes. In Romanian population and neighboring countries, several recurrent mutations have already been described. In a consecutive series of 50 sporadic ovarian cancer patients, not qualifying for BRCA complete testing, we screened for 9 most common BRCA mutations, by multiplex-PCR, RFLP and targeted Sanger sequencing. Our results revealed 6 different BRCA mutations in 8 unrelated patients, with a frequency of 16%, much higher than expected. We further recommend screening for the identified mutations in larger series of cancer patients. The results are highly beneficial to cancer patients, healthy relatives, and overall, considering prevention in cancer a priority, to public health system and future of oncogenetics in Romania


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e23010-e23010
Author(s):  
Vanessa Carranza ◽  
Bryan Carson Taylor ◽  
Susan H. Gitzinger ◽  
Joan B. Fowler ◽  
Jessica Hall

e23010 Background: About a third of ovarian cancer patients in the US have limited access to a gynecologic oncologist (GO) due to geographic disparities. A survey by The Society of Gynecologic Oncology (SGO) found that the majority of GOs found it was vital to coordinate local access to care, from diagnosis to survivorship, for patients living in areas of disparity. This allows rural/underserved patients broader access to novel therapies, as they increasingly become standard of care. It is critical for not only GOs to be current on the latest ovarian cancer data, but all clinicians who care for these patients. Methods: CEC Oncology developed two educational initiatives focused on PARP inhibitor therapy in ovarian cancer, which was targeted to all US healthcare professionals caring for ovarian cancer patients. Evaluations were collected from attendees attending an SGO Symposium and Ground Round (GR) series to assess impact on practice, increased competency, and intent to make a change in practice. Learning, knowledge, and competence was objectively assessed by analyzing pre-test, post-test, and follow-up survey data (sent 4-6 weeks post-activity). Chi-square analysis was conducted with a priori significance set at 0.05. Results: A total of 830 clinicians were educated, with SGO attendees primarily practicing in academic settings and GR attendees mostly from community practices. SGO attendees were asked case questions at baseline, immediately after the activity, and 4-6 weeks after the activity. Knowledge increased from pre- to post-test regarding current genetic testing recommendations (23% increase; P= .004) and appropriate selection of PARP inhibitor therapy (25% increase; P= .017). Knowledge was sustained at follow-up analysis. At follow-up, 90% of SGO and 84% of GR attendees made a change as a result of attending the activities. More attendees were able to incorporate germline multigene testing into practice, than originally intended; increase of 29% for SGO and 7% for GR audiences. All attendees experienced the barrier lack of patient education about the importance of genetic testing/counseling more than anticipated; increase of 7% for SGO and 13% for GR audiences. At follow-up, there was a 9% increase in GR attendees listing staying current with trial data and practice guidelines as a barrier. Conclusions: There were some notable differences seen in competence/performance among attendees of the two ovarian cancer educational initiatives. Differences may be attributed to practice setting (SGO primarily academic; GR primarily community.) Overall, GR attendees were more likely to face barriers, suggesting that community-based clinicians have fewer resources and experience more barriers to implementing best practices. Thus, it is vital to offer education for clinicians in community-based practices, particularly in areas that are considered ‘geographically disparate’.


Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3026
Author(s):  
Amos Stemmer ◽  
Inbal Shafran ◽  
Salomon M. Stemmer ◽  
Daliah Tsoref

Background: Three PARPis (olaparib, niraparib and rucaparib) are currently FDA-approved as maintenance therapy in newly diagnosed and recurrent ovarian cancer. However, thus far, no trial has compared the three approved PARPis in the overall population, in patients with BRCA mutations, or in those with wild-type BRCA. Methods: A frequentist network meta-analysis was used for indirect comparisons between the different PARPis with respect to progression free survival (PFS), overall survival (OS), and adverse events. Results: Overall, six randomized clinical trials involving 2,770 patients, were included in the analysis. Results from the indirect comparisons revealed no statistically significant differences between the three PARPis with respect to PFS or OS in the entire population and in patients with mutated and wild-type BRCA, separately. Niraparib showed a statistically significant increased risk for grade 3 and 4 thrombocytopenia (risk-difference [RD] from placebo: 0.3; 95% confidence interval [CI], 0.27‒0.34) and any grade neutropenia (RD from placebo: 0.22; 95% CI, 0.18‒0.25) as compared with the other PARPis. Conclusion: No statistically significant difference was found between the three PARPis with respect to PFS or OS (overall and in subpopulations by BRCA status). There is, however, a statistical difference in toxicity as niraparib is associated with a greater risk for thrombocytopenia and neutropenia.


ESMO Open ◽  
2020 ◽  
Vol 5 (6) ◽  
pp. e001110
Author(s):  
Susana Banerjee ◽  
Antonio Gonzalez-Martin ◽  
Philipp Harter ◽  
Domenica Lorusso ◽  
Kathleen N Moore ◽  
...  

Poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is the latest breakthrough in the management of newly diagnosed advanced ovarian cancer. The results of the SOLO-1 trial in 2018 led to European Medicines Agency and Food and Drug Administration approval of olaparib as first-line maintenance therapy in patients with BRCA1/2 mutation, establishing a new standard of care. Subsequently, the results of three phase III trials (PRIMA, PAOLA-1, VELIA) evaluating the use of first-line PARP inhibitors beyond patients with BRCA1/2 mutations and as combination strategies were presented in 2019, leading to the recent approval of maintenance niraparib irrespective of biomarker status and olaparib in combination with bevacizumab in homologous recombination deficiency-positive-associated advanced ovarian cancer. An ESMO Open - Cancer Horizons round-table expert panel discussed the four phase III trials of first-line PARP inhibitor therapy and how they are changing the clinical management of advanced ovarian cancer.


2016 ◽  
Author(s):  
Iain A. McNeish ◽  
Kevin K. Lin ◽  
James X. Sun ◽  
Sandra Goble ◽  
Amit Oza ◽  
...  

Author(s):  
Rebecca S. Kristeleit ◽  
Rowan E. Miller ◽  
Elise C. Kohn

The presence of a BRCA mutation, somatic or germline, is now established as a standard of care for selecting patients with ovarian cancer for treatment with a PARP inhibitor. During the clinical development of the PARP inhibitor class of agents, a subset of women without BRCA mutations were shown to respond to these drugs (termed “ BRCAness”). It was hypothesized that other genetic abnormalities causing a homologous recombinant deficiency (HRD) were sensitizing the BRCA wild-type cancers to PARP inhibition. The molecular basis for these other causes of HRD are being defined. They include individual gene defects (e.g., RAD51 mutation, CHEK2 mutation), homozygous somatic loss, and whole genome properties such as genomic scarring. Testing this knowledge is possible when selecting patients to receive molecular therapy targeting DNA repair, not only for patients with ovarian cancer but also endometrial and cervical cancers. The validity of HRD assays and multiple gene sequencing panels to select a broader population of patients for treatment with PARP inhibitor therapy is under evaluation. Other non-HRD targets for exploiting DNA repair defects in gynecologic cancers include mismatch repair (MMR), checkpoint signaling, and nonhomologous end-joining (NHEJ) DNA repair. This article describes recent evidence supporting strategies in addition to BRCA mutation for selecting patients for treatment with PARP inhibitor therapy. Additionally, the challenges and opportunities of exploiting DNA repair pathways other than homologous recombination for molecular therapy in gynecologic cancers is discussed.


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