In the past few years, the advent of PARP inhibitors has been a revolution in the management of ovarian cancer. Patients harboring somatic or germ line BRCA1/2 mutations exhibit different clinical ...and treatment response behavior. The BRCA gene is involved in repairing DNA repair via homologous recombination, and mutation of this gene leads to homologous recombination deficiency (HRD).
HRD constitutes a therapeutic opportunity for these patients, thanks to the development of poly(ADP-ribose) polymerase inhibitors (PARPi) in the late 2000s. Indeed, using PARPi in patients with HRD simultaneously compromises two mechanisms of DNA repair, resulting in synthetic lethality.
This breakthrough in clinical practice has raised remaining questions: which population will most benefit from PARPi? Are all ovarian cancers susceptible to synthetic lethal strategy? At which stage of ovarian cancer should PARPi be used? Is earlier always better? Are PARPi all equivalent? Which strategies are reasonable to overcome PARPi resistance? Which combination strategies should be efficient?
Gynecological carcinosarcomas are rare and aggressive diseases, with a poor prognosis. The rarity of these tumors explains the lack of robust and specific data available in the literature. The ...objective of this study was to investigate the impact of initial adjuvant treatment and recurrent therapeutic strategies.
A multicentric cohort study within the French national prospective Rare Malignant Gynecological Tumors (TMRG) network was conducted. Data from all included carcinosarcomas diagnosed between 2011 and 2018 were retrospectively collected.
425 cases of uterine and ovarian carcinosarcomas (
= 313 and
= 112, respectively) were collected and analyzed from 12 participating centers. At diagnosis, 140 patients (48%) had a FIGO stage III-IV uterine carcinosarcoma (UCS) and 88 patients (83%) had an advanced ovarian carcinosarcoma (OCS) (FIGO stage ≥ III). Two hundred sixty-seven patients (63%) received adjuvant chemotherapy, most preferably carboplatin-paclitaxel regimen (
= 227, 86%). After a median follow-up of 47.4 months, the median progression-free survival (mPFS) was 15.1 months (95% CI 12.3-20.6) and 14.8 months (95% CI 13.1-17.1) for OCS and UCS, respectively. The median overall survival for OCS and UCS was 37.1 months (95% CI 22.2-49.2) and 30.6 months (95% CI 24.1-40.9), respectively. With adjuvant chemotherapy followed by radiotherapy, mPFS was 41.0 months (95% CI 17.0-NR) and 18.9 months (95% CI 14.0-45.6) for UCS stages I-II and stages III-IV, respectively. In the early stage UCS subgroup (i.e., stage IA,
= 86, 30%), mPFS for patients treated with adjuvant chemotherapy (
= 24) was not reached (95% CI 22.2-NR), while mPFS for untreated patients (
= 62) was 19.9 months (95% IC 13.9-72.9) (HR 0.44 (0.20-0.95)
= 0.03). At the first relapse, median PFS for all patients was 4.2 months (95% CI 3.5-5.3). In the first relapse, mPFS was 6.7 months (95% CI 5.1-8.5) and 2.2 months (95% CI 1.9-2.9) with a combination of chemotherapy or monotherapy, respectively (
< 0.001).
Interestingly, this vast prospective cohort of gynecological carcinosarcoma patients from the French national Rare Malignant Gynecological Tumors network (i) highlights the positive impact of adjuvant CT on survival in all localized stages (including FIGO IA uterine carcinosarcomas), (ii) confirms the importance of platinum-based combination as an option for relapse setting, and (iii) reports median PFS for various therapeutic strategies in the relapse setting.
Background: In spite of the frequency and clinical impact of BRCA1/2 alterations in high-grade epithelial ovarian cancer (HGEOC), real-world information based on robust data warehouse has been scarce ...to date. Methods: Consecutive patients with BRCA-mutated HGEOC treated between 2011 and 2016 within French comprehensive cancer centers from the Unicancer network were extracted from the ESME database. The main objective of the study was the assessment of clinicopathological and treatments parameters. Results: Out of the 8021 patients included in the ESME database, 266 patients matching the selection criteria were included. BRCA1 mutation was found in 191 (71.8%) patients, while 75 (28.2%) had a BRCA2 mutation only; 95.5% of patients received a cytoreductive surgery. All patients received a taxane/platinum-based chemotherapy (median = six cycles). Complete and partial response were obtained in 53.3% and 20.4% of the cases, respectively. Maintenance therapy was administered in 55.3% of the cases, bevacizumab being the most common agent. After a median follow up of 51.7 months, a median progression-free survival of 28.6 months (95% confidence interval (CI) 26.5; 32.7) and an estimated 5-year median overall survival of 69.2% (95% CI 61.6; 70.3) were reported. Notably, BRCA1- and BRCA2-mutated cases exhibited a trend towards different median progression-free survivals, with 28.0 (95% CI 24.4; 32.3) and 33.3 months (95% CI 26.7; 46.1), respectively (p-value = 0.053). Furthermore, five-year OS for BRCA1-mutated patients was 64.5% (95% CI 59.7; 69.2), while it was 82.5% (95% CI 76.6; 88.5) for BRCA2-mutated ones (p-value = 0.029). Conclusions: This study reports the largest French multicenter cohort of BRCA-mutated HGEOCs based on robust data from the ESME, exhibiting relevant real-world data regarding this specific population.
Identifying prognostic factors and evaluating the impact of adjuvant chemotherapy in patients with sex cord stromal tumors (SCST) is crucial. In this study, we aimed to address these challenges.
We ...conducted a retrospective analysis of data from 13 centers of the French Rare malignant gynecological tumors (TMRG) network. We enrolled 469 adult patients with malignant SCST who received upfront surgery since 2011 to July 2015.
75% were diagnosed with adult Granulosa cell tumors, and 23% had another subtype. With a median follow-up of 6.4 years, 154 patients (33%) developed a first recurrence, 82 (17%) two recurrences, and 49 (10%) three recurrences. Adjuvant chemotherapy was administered in 14.7% of patients at initial diagnosis. In relapse, perioperative chemotherapy was administered in 58.5%, 28.2%, and 23.8% of patients, respectively, in the first, second, and third relapse.
In the first-line therapy, age under 70 years, FIGO stage, and complete surgery were associated with longer progression-free survival (PFS). Chemotherapy had no impact on PFS in early-stage disease (FIGO I-II). The PFS was similar using BEP or other chemotherapy regimens (HR 0.88 0.43; 1.81) in the first-line therapy. In case of recurrence, PFS was statistically prolonged by complete surgery, but perioperative chemotherapy use did not impact PFS.
Chemotherapy use did not impact survival in the first-line or relapse setting in SCST. Only surgery and its quality demonstrated benefit for PFS in ovarian SCST in any lines of treatment.
•Surgery remains the mainstay of treatment for sex cord stromal tumors (SCST) in both the initial treatment and relapses.•Adjuvant Chemotherapy does not improve PFS for patients in 1st line setting with stage I-II but also in relapse setting•Adjuvant chemotherapy with BEP does not appear to improve PFS compared to other regimes.
Carboplatin and pegylated liposomal doxorubicin combination is a standard regimen in platinum-sensitive recurrent ovarian cancer patients. The pegylated liposomal doxorubicin shortage from 2011 to ...2013 urged assessment of the efficacy and tolerance of non-pegylated liposomal doxorubicin in combination with carboplatin.
MYCA was a multicenter 2-step phase Ib-II single arm trial meant to assess the safety and efficacy of carboplatin AUC 5 mg/min.mL combined with non-pegylated liposomal (dose escalation from 40 to 50 mg/m2 during phase Ib step; and 50 mg/m2 during phase II step), every 4 weeks in patients with platinum-sensitive relapse. The primary objective was disease control rate (DCR) at 12 months.
From 2012 to 2014, 87 patients were enrolled. They were treated as second (78%) or third line (22%) treatment. Total of 67 patients (78%) completed 6 cycles. G-CSF support was prescribed to 58% patients. The DCR at 12 months was 30.0% (95% CI, 20.3–39.7); the median PFS was 10.0 months (95% CI, 8.6–11.0). The median overall survival was 28.1 months (95% CI, 22.3–32.5); and the objective response rate was 58% (95% CI, 47–68). Grade 3–4 neutropenia, anemia and thrombocytopenia were observed in 17%, 13% and 1%, respectively; febrile neutropenia in 6%. One patient who did not receive GCSF support died from febrile neutropenia.
Non-pegylated liposomal doxorubicin-carboplatin combination exhibits an acceptable safety profile, with GCSF prophylaxis. Acknowledging the lack of direct comparison, efficacy in terms of 12 month DCR was comparable with standard treatments.
•Carboplatin + non-pegylated liposomal doxorubicin (NPLD) is effective in platinum-sensitive recurrent ovarian cancers.•The disease control rate at 12 months was 30%.•This combination is well tolerated but should be prescribed with G-CSF support.•NPLD could be an alternative to pegylated liposomal doxorubicin in association with carboplatin.
BRCA-mutated high-grade epithelial ovarian cancers represent a specific subset of gynecological malignancies. Real-world comprehensive data have been elusive to date. As such, we conducted a ...comprehensive description of clinicopathological and therapeutical characteristics via the Epidemiological Strategy and Medical Economics (ESME) data warehouse, which collects data from 18 French comprehensive cancer centers from the Unicancer network. This led to useful findings regarding the natural disease history of these patients in clinical practice, prior to the advent of poly-ADP ribose polymerase inhibitors. Background: In spite of the frequency and clinical impact of BRCA1/2 alterations in high-grade epithelial ovarian cancer (HGEOC), real-world information based on robust data warehouse has been scarce to date. Methods: Consecutive patients with BRCA-mutated HGEOC treated between 2011 and 2016 within French comprehensive cancer centers from the Unicancer network were extracted from the ESME database. The main objective of the study was the assessment of clinicopathological and treatments parameters. Results: Out of the 8021 patients included in the ESME database, 266 patients matching the selection criteria were included. BRCA1 mutation was found in 191 (71.8%) patients, while 75 (28.2%) had a BRCA2 mutation only; 95.5% of patients received a cytoreductive surgery. All patients received a taxane/platinum-based chemotherapy (median = six cycles). Complete and partial response were obtained in 53.3% and 20.4% of the cases, respectively. Maintenance therapy was administered in 55.3% of the cases, bevacizumab being the most common agent. After a median follow up of 51.7 months, a median progression-free survival of 28.6 months (95% confidence interval (CI) 26.5; 32.7) and an estimated 5-year median overall survival of 69.2% (95% CI 61.6; 70.3) were reported. Notably, BRCA1- and BRCA2-mutated cases exhibited a trend towards different median progression-free survivals, with 28.0 (95% CI 24.4; 32.3) and 33.3 months (95% CI 26.7; 46.1), respectively (p-value = 0.053). Furthermore, five-year OS for BRCA1-mutated patients was 64.5% (95% CI 59.7; 69.2), while it was 82.5% (95% CI 76.6; 88.5) for BRCA2-mutated ones (p-value = 0.029). Conclusions: This study reports the largest French multicenter cohort of BRCA-mutated HGEOCs based on robust data from the ESME, exhibiting relevant real-world data regarding this specific population.
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