Prevalence of germline BRCA1 and BRCA2 mutations and variants among ovarian, primary peritoneal and fallopian tube cancer patients: A multicentre Indian study

Gupta, Sudeep; Rajappa, Senthill J; Advani, SH; Agarwal, Amit; Aggarwal, Sandeep; Goswami, Chanchal; Palanki, Satya Dattatreya; Arya, Devavrat; Patil, Shekar; Kodagali, Rohit

doi:10.1093/annonc/mdz426.002

Cited by 4 publications

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“…In the studies that evaluated single-agent chemotherapy with or without bevacizumab in PROC, the 2-year OS ranged between 20% and 35%. 27 - 29 This suggests that PARPi can be evaluated as a treatment option in gBRCAm cases. This needs to be proven in randomized trials.…”

Section: Discussionmentioning

confidence: 99%

PARP Inhibitor in Platinum-Resistant Ovarian Cancer: Single-Center Real-World Experience

Agarwal

Baghmar

Dodagoudar

et al. 2021

JCO Global Oncology

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PURPOSE Poly (ADP-ribose) polymerase inhibitors (PARPi) have proven efficacy in treatment of BReast CAncer ( BRCA) gene mutation-positive platinum-sensitive ovarian cancers. There is paucity of data for their role in platinum-resistant ovarian cancer (PROC). We report here retrospective analysis of outcome of PARPi treatment in a group of patients including those of PROC. PATIENTS AND METHODS We analyzed all consecutive patients who received PARPi. The efficacy of PARPi monotherapy was assessed in patients with relapsed high-grade serous ovarian carcinoma with g BRCAm. The drug was procured through compassionate program. Drugs (olaparib and talazoparib) were provided in capsule form. RESULTS Between July 1, 2015, and June 30, 2019, 28 patients with ovarian cancer received PARPi. At the time of data censoring (September 30, 2019), four (14.3%) patients are still on treatment. Median age was 54.5 years (range, 39-75 years). Median number of previous lines of chemotherapy received was three (range, 1-6). Eleven platinum-sensitive patients received the drug as maintenance (five in complete response and six in partial response after chemotherapy), whereas 17 (60.7%) had platinum-resistant progressive disease while starting the drug. In PROC, objective response rate (complete response plus partial response) was 47%, median progression-free survival was 8.2 months (5.3-11.3), and overall survival was 14.9 months (11.2-18.5). No new side effects were observed. CONCLUSION This is the first study from India evaluating PARPi in platinum-resistant ovarian cancer. This study suggests that PARPi is a viable treatment option in patients with PROC with gBRCAm. This should be further evaluated in randomized clinical trial.

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Section: Discussionmentioning

confidence: 99%

PARP Inhibitor in Platinum-Resistant Ovarian Cancer: Single-Center Real-World Experience

Agarwal

Baghmar

Dodagoudar

et al. 2021

JCO Global Oncology

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“…In EOC, germline BRCA (gBRCA ) mutations are identified in 13 to 15% of the cases and somatic BRCA mutations are found in 5 to 10% of the cases [11,12]. The incidence of gBRCA mutation varies widely based on the ethnicity (8 to 17% in Caucasians compared with 15 to 30% in Asians) [13][14][15][16][17][18]. Mutations that interfere with normal function of BRCA are reported to modulate outcomes of treatment with platinum/molecular-targeted drugs [19,20].…”

Section: Introductionmentioning

confidence: 99%

Maintenance therapy for newly diagnosed epithelial ovarian cancer– a review

et al. 2022

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Epithelial ovarian cancer (EOC) is the most lethal gynaecological cancer among women worldwide, with the 5-year survival rate ranging between 30 and 40%. Due to the asymptomatic nature of the condition, it is more likely to be diagnosed at an advanced stage, requiring an aggressive therapeutic approach. Cytoreductive surgery (CRS) along with systemic chemotherapy with paclitaxel and carboplatin has been the mainstay of the treatment in the frontline management of EOC. In recent years, neo-adjuvant chemotherapy, followed by interval CRS has become an important strategy for the management of advanced EOC. Due to the high rate of recurrence, the oncology community has begun to shift its focus to molecular-targeted agents and maintenance therapy in the frontline settings. The rationale for maintenance therapy is to delay the progression or relapse of the disease, as long as possible after first-line treatment, irrespective of the amount of residual disease. Tumours with homologous recombination deficiency (HRD) including BReast CAncer gene (BRCA) mutations are found to be sensitive to polyadenosine diphosphate-ribose polymerase (PARP) inhibitors and understanding of HRD status has become important in the frontline setting. PARP inhibitors are reported to provide a significant improvement in progression-free survival and have an acceptable safety profile. PARP inhibitors have also been found to act regardless of BRCA status. Recently, PARP inhibitors as maintenance therapy in the frontline settings showed encouraging results in EOC; however, the results from further trials and survival data from ongoing trials are awaited for understanding the role of this pathway in treatment of EOC. This review discusses an overview of maintenance strategies in newly diagnosed EOC along with considerations for maintenance therapy in EOC with a focus on PARP inhibitors.

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