Handle with care – effektives Toxizitätsmanagement während Chemotherapie eines serösen high-grade Ovarialkarzinoms

2021 ◽  
Vol 53 (04) ◽  
pp. 179-182
Author(s):  
Peter Holzhauer
Keyword(s):  
Parp Inhibitor ◽  
Brca2 Mutation ◽  
High Grade ◽  
Genetische Testung ◽  
Maligne Erkrankung ◽  
Carboplatin Auc

ZusammenfassungHier wird der komplikationsreiche Behandlungsverlauf einer heute 50-jährigen Patientin dargestellt. Operativ konnte bei schon weit fortgeschrittener Peritonealkarzinose keine Tumorfreiheit erreicht werden. Wegen des sehr reduzierten Allgemeinzustands war initial nur eine Monochemotherapie mit Carboplatin AUC 5 möglich. Unter dieser deeskalierten Monotherapie kam es schon nach dem ersten Zyklus zu einer ausgeprägten Hämatotoxizität mit behandlungsbedürftiger Anämie, Thrombopenie sowie Leukopenie, sodass mehrmalige Transfusionen von Erythrozyten- und Thrombozytenkonzentraten und G-CSF-Gaben notwendig wurden. Die weiteren Zyklen mussten mit erheblich reduzierter Dosierung angepasst werden. Unter dieser suboptimalen Dosierung war die maligne Erkrankung progredient, die Patientin musste einen Sigmastent bei symptomatischer Sigmastenose erhalten.Ab diesem Zeitpunkt wurde die weitere Behandlung der Patientin in einem intensiven komplementär/supportiven Konzept und mit einer individualisierten Chemotherapiekombination fortgeführt. Darunter kam es zu einer rückläufigen Hämatotoxizität, die Chemotherapie konnte nach 6 Zyklen mit einer weitgehenden Remission aller Tumormanifestationen beendet werden. Die genetische Testung ergab eine BRCA2-Mutation. Daraufhin erhielt die Patientin eine orale Erhaltungstherapie mit dem PARP-Inhibitor Niraparib 4.

Maintenance olaparib plus bevacizumab (bev) after platinum-based chemotherapy plus bev in patients (pts) with newly diagnosed advanced high-grade ovarian cancer (HGOC): Efficacy by BRCA1 or BRCA2 mutation in the phase III PAOLA-1 trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6039-6039
Author(s):  
Domenica Lorusso ◽  
Jean-Pierre Lotz ◽  
Philipp Harter ◽  
Claire Cropet ◽  
Maria Jesus Rubio Pérez ◽  
...  
Keyword(s):  
Brca Mutation ◽  
Brca1 Mutation ◽  
Parp Inhibitor ◽  
Brca2 Mutation ◽  
Phase Iii ◽  
Primary Data ◽  
High Grade ◽  
Newly Diagnosed ◽  
First Line ◽  
Platinum Based Chemotherapy

6039 Background: In PAOLA-1/ENGOT-ov25 (NCT02477644), adding the PARP inhibitor olaparib to maintenance bev after first-line platinum-based chemotherapy plus bev led to a statistically significant progression-free survival (PFS) benefit in pts with advanced HGOC (HR 0.59; 95% CI 0.49–0.72) (Ray-Coquard et al. 2019). Retrospective subgroup analysis in GOG-0218 (Norquist et al. 2018) suggested BRCA mutation (BRCAm) status did not significantly impact the PFS benefit provided by bev. We explored the efficacy of olaparib plus bev by BRCA1 mutation ( BRCA1m) or BRCA2 mutation ( BRCA2m) in PAOLA-1. Methods: PAOLA-1 is a randomized, double-blind, Phase III trial in pts with newly diagnosed, FIGO stage III–IV, high-grade serous or endometrioid OC, fallopian tube or primary peritoneal cancer receiving platinum-based chemotherapy plus bev then maintenance bev. Pts unrestricted by surgical outcome or BRCAm status and in response to first-line therapy were randomized to maintenance olaparib tablets (300 mg bid for up to 24 months) plus bev (15 mg/kg q3w for up to 15 months in total) or placebo plus bev, stratified by first-line treatment outcome and tumor BRCAm status. Investigator-assessed PFS (modified RECIST v1.1) by BRCAm was a predefined analysis. Results: Of 806 randomized pts, 160 (20%) had tumor BRCA1m, 76 (9%) had tumor BRCA2m and 1 (<1%) had both. Median PFS follow-up was 24.1 and 27.4 months in BRCA1m and BRCA2m pts, respectively. At primary data cutoff, PFS was prolonged with olaparib plus bev versus placebo plus bev in BRCA1m pts and BRCA2m pts (Table). The percentage of BRCA1m pts who received olaparib plus bev and were progression-free at 1 and 2 years was 95% and 73% (vs. 70% and 29% for placebo plus bev) and for BRCA2m pts was 89% and 84% (vs. 84% and 53%) (Kaplan-Meier estimates). Conclusions: In PAOLA-1, maintenance olaparib plus bev provided a significant PFS benefit versus placebo plus bev in all pts analysed, regardless of whether they had BRCA1m or BRCA2m. The median PFS in the control arm suggests a role for bev in this subgroup and the hazard ratio versus an active control arm shows the value of adding maintenance olaparib to bev. Clinical trial information: NCT02477644. [Table: see text]

ARIEL4: An international, multicenter randomized phase 3 study of the PARP inhibitor rucaparib vs chemotherapy in germline or somatic BRCA1- or BRCA2-mutated, relapsed, high-grade ovarian carcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS5603-TPS5603 ◽  
Author(s):  
Amit M. Oza ◽  
Domenica Lorusso ◽  
Ana Oaknin ◽  
Tamar Safra ◽  
Elizabeth Swisher ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Parp Inhibitor ◽  
Brca2 Mutation ◽  
Single Agent ◽  
Objective Response ◽  
The United States ◽  
Parp Inhibitors ◽  
Ca 125 ◽  
High Grade ◽  
Platinum Sensitive

TPS5603 Background: In high-grade epithelial ovarian carcinoma (OC), ≈18% of patients (pts) have tumors with a germline BRCA1 or BRCA2 mutation; ≈7% have tumors with a somatic BRCA1 or BRCA2 mutation (Pennington et al. Clin Cancer Res. 2014;20:764-75). The poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib is approved in the United States for treatment of pts with OC associated with a deleterious BRCA1 or BRCA2 mutation (germline and/or somatic) who have received ≥2 chemotherapies. Although PARP inhibitors have demonstrated clinical activity in OC in both treatment and maintenance settings, comparison to standard of care (SOC) has only been evaluated in the maintenance setting. Randomized studies are needed to assess the benefit-risk profile of PARP inhibitors vs current SOC as treatment for BRCA1- or BRCA2-mutated, relapsed, high-grade OC. Methods: ARIEL4 (NCT02855944) is evaluating rucaparib vs chemotherapy as treatment for pts with germline or somatic BRCA1- or BRCA2-mutated, relapsed, high-grade OC (regardless of histology) who have received ≥2 prior chemotherapy regimens. Approximately 345 pts will be randomized 2:1 to receive rucaparib (600 mg BID) (n = 230) or chemotherapy (n = 115) and stratified by progression-free interval after their most recent platinum regimen. Pts with platinum-resistant (progressive disease [PD] 1– < 6 mo after last platinum) or partially platinum-sensitive disease (PD 6– < 12 mo after last platinum) will be randomized to rucaparib or weekly paclitaxel; pts with platinum-sensitive disease (PD ≥12 mo after last platinum) will be randomized to rucaparib or platinum-based therapy (single-agent or doublet at the discretion of the investigator). Pts receiving chemotherapy have the option to cross over to rucaparib upon radiographic disease progression. The primary endpoint is progression-free survival. Secondary endpoints include investigator-assessed objective response rate (ORR) (RECIST version 1.1), ORR/CA-125 response, duration of response, overall survival, and pt-reported outcomes. Safety will be summarized descriptively using standard adverse event reporting. Clinical trial information: NCT02855944.

BRCA Reversion Mutations in Circulating Tumor DNA Predict Primary and Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma

2018 ◽  
Vol 9 (2) ◽  
pp. 210-219 ◽  
Author(s):  
Kevin K. Lin ◽  
Maria I. Harrell ◽  
Amit M. Oza ◽  
Ana Oaknin ◽  
Isabelle Ray-Coquard ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Parp Inhibitor ◽  
Acquired Resistance ◽  
Circulating Tumor Dna ◽  
High Grade ◽  
Tumor Dna

scholarly journals Precision Oncology of High-Grade Ovarian Cancer Defined through Targeted Sequencing

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5240
Author(s):  
Sandra Wessman ◽  
Beatriz Bohorquez Fuentes ◽  
Therese Törngren ◽  
Anders Kvist ◽  
Georgia Kokaraki ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Molecular Characterization ◽  
Parp Inhibitor ◽  
Clinical Information ◽  
Undifferentiated Carcinoma ◽  
Serous Carcinoma ◽  
Precision Oncology ◽  
High Grade ◽  
Histologic Diagnosis ◽  
Germline Testing

Background: We examined whether molecular characterization of high-grade epithelial ovarian cancer can inform the diagnosis and/or identify potential actionable targets. Methods: All of the consecutively sequenced high-grade ovarian tumours with consent between 2014 until 2019 were included. A total of 274 tumours underwent next generation sequencing using a targeted panel. Results: Patients with high-grade ovarian epithelial cancer were consented to prospective molecular characterization. Clinical information was extracted from their medical record. Tumour DNA was subjected to sequencing, and selected patients received PARP inhibitor therapy. Conclusions: Tumours from 274 women were sequenced, including high-grade serous carcinoma (n = 252), clear cell carcinoma (n = 4), carcinosarcoma (n = 9), endometrioid carcinoma (n = 3), undifferentiated carcinoma (n = 1), and mixed tumours (n = 5). Genomic profiling did not influence histologic diagnosis. Mutations were identified in TP53, BRCA1, BRCA2, as well as additional homologous recombination repair pathway genes BARD1, ATR, CHEK2, PALB2, RAD51D, RAD50, SLX4, FANCA, RAD51C, and RAD54L. In addition, mutations in PTEN and CDKN2A were identified. Several somatic mutations with implications for germline testing were identified, including RMI1, STK11, and CDH1. Germline testing identified 16 previously unknown BRCA1/2 carriers. Finally, 20 patients were treated with the PARP inhibitor olaparib based on the sequencing results.

scholarly journals ARIEL4: An international, randomised phase 3 study of the PARP inhibitor rucaparib vs chemotherapy for the treatment of BRCA-mutated, relapsed, high-grade ovarian cancer

2017 ◽  
Vol 28 ◽  
pp. v352
Author(s):  
R.S. Kristeleit ◽  
D. Lorusso ◽  
A. Oaknin ◽  
T. Safra ◽  
E.M. Swisher ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Parp Inhibitor ◽  
High Grade ◽  
Phase 3

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.

Sign in / Sign up

Export Citation Format

Share Document