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Margarita Amenedo Gancedo

Bio: Margarita Amenedo Gancedo is an academic researcher. The author has contributed to research in topics: Internal medicine & Oncology. The author has an hindex of 1, co-authored 1 publications receiving 735 citations.

Papers
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Journal ArticleDOI
Robert L. Coleman1, Amit M. Oza2, Domenica Lorusso, Carol Aghajanian3, Ana Oaknin4, Andrew Dean, Nicoletta Colombo5, Johanne I Weberpals6, Andrew R Clamp7, Giovanni Scambia8, Alexandra Leary9, Robert W Holloway, Margarita Amenedo Gancedo, Peter C.C. Fong10, Jeffrey C. Goh11, David M. O'Malley12, Deborah K. Armstrong13, Jesus Garcia-Donas, Elizabeth M. Swisher14, Anne Floquet, Gottfried E. Konecny15, Iain A. McNeish16, Clare L. Scott17, Terri Cameron, Lara Maloney, Jeff Isaacson, Sandra Goble, Caroline Grace, Thomas Harding, Mitch Raponi, James Sun18, Kevin K. Lin, Heidi Giordano, Jonathan A. Ledermann19, Martin Buck, A Dean, Michael Friedlander, J C Goh11, Paul R. Harnett, G Kichenadasse20, C L Scott17, H Denys, Luc Dirix, Ignace Vergote, Laurie Elit, Prafull Ghatage, Amit M. Oza2, Marie Plante, Diane Provencher, J I Weberpals6, Stephen Welch, A Floquet, Laurence Gladieff, Florence Joly, A Leary9, Alain Lortholary, Jean-Pierre Lotz, J. Medioni, Olivier Tredan, Benoit You, A El-Balat, C Hänle, P Krabisch, T Neunhöffer, M Pölcher, Pauline Wimberger, Amnon Amit, S Kovel, M Leviov, Tamar Safra, Ronnie Shapira-Frommer, Salomon M. Stemmer, Alessandra Bologna, N Colombo5, Domenica Lorusso, Sandro Pignata, Roberto Sabbatini, G Scambia8, Stefano Tamberi, Claudio Zamagni, P C Fong10, A O'Donnell, M Amenedo Gancedo, A Casado Herraez, J Garcia-Donas, E M Guerra, A Oaknin4, I Palacio, Iris L. Romero, A Sanchez, Susana Banerjee, A Clamp7, Y Drew, Hani Gabra, D Jackson, Jonathan A. Ledermann19, I A McNeish16, Christine Parkinson, Melanie E Powell, C Aghajanian3, D K Armstrong13, Michael J. Birrer, Mary K. Buss, Setsuko K. Chambers, L-m Chen, Robert L. Coleman1, R W Holloway, G E Konecny15, L Ma, Mark A. Morgan, R T Morris, David G. Mutch, D M O'Malley12, B M Slomovitz, E M Swisher14, T Vanderkwaak, M Vulfovich 
TL;DR: This trial assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity.

1,139 citations

Proceedings ArticleDOI
01 Oct 2022
TL;DR: The ARIEL3 study as mentioned in this paper showed that progression-free survival (PFS) improved significantly with rucaparib maintenance treatment versus placebo, and the PFS benefit was maintained through the next subsequent line of therapy.
Abstract:

Introduction/Background

In ARIEL3 (NCT01968213), progression-free survival (PFS) improved significantly with rucaparib maintenance treatment versus placebo. We present updated PFS2 and preplanned final overall survival (OS) analyses.

Methodology

ARIEL3 enrolled patients with platinum-sensitive, high-grade ovarian carcinoma who had received ≥2 previous platinum-based chemotherapy regimens and had responded to their last platinum-based regimen. Patients were randomised 2:1 to receive rucaparib 600 mg twice daily or placebo, with 3 protocol-defined nested cohorts: BRCA-mutant, homologous recombination deficient (HRD) and intent-to-treat (ITT). Efficacy outcomes for the nested cohorts included the secondary endpoint of OS (with analysis planned after 70% of events) and the exploratory endpoint of PFS2 (defined as time from randomisation to second event of investigator-assessed disease progression or death due to any cause). Patients were followed for the incidence of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). Data cutoff dates were 31 December 2019 (safety), 4 April 2022 (efficacy) and 12 April 2022 (monitoring of MDS/AML).

Results

After a median follow-up of 77.0 months in the ITT population, 410/564 (72.7%) of OS events had occurred. OS and PFS2 are presented in table 1. A PARP inhibitor was administered as subsequent treatment to ≈45% of patients who received placebo. Safety data were consistent with those of prior reports. MDS/AML was reported in 14 (3.8%) and 6 (3.2%) patients in the rucaparib and placebo arms, respectively (P=0.72). Among these, 8 patients in the rucaparib arm and 6 in the placebo arm developed MDS/AML after completion of study drug treatment.

Conclusion

These data support the use of rucaparib as a maintenance treatment for recurrent ovarian carcinoma. Although no OS benefit was observed, the PFS benefit for rucaparib was maintained through the next subsequent line of therapy.

6 citations

Proceedings ArticleDOI
01 Dec 2022
TL;DR: Rucaparib as discussed by the authors showed that maintenance treatment significantly improved progression-free survival (PFS) vs placebo compared to placebo, and the PFS benefit was maintained through subsequent line of therapy.
Abstract:

Objectives

In ARIEL3 (NCT01968213), rucaparib maintenance treatment significantly improved progression-free survival (PFS) vs placebo. We present updated PFS2 and preplanned final overall survival (OS) analyses.

Methods

Patients were randomized to receive rucaparib 600 mg BID or placebo. Efficacy was analyzed across the 3 protocol-defined nested cohorts (BRCA-mutant, homologous recombination deficient [HRD], and intent-to-treat [ITT]). PFS2 was an exploratory endpoint, defined as time from randomization to second event of investigator-assessed disease progression, or death due to any cause. OS was a secondary endpoint with analysis planned after 70% of death events. The data cutoff was April 4, 2022, for efficacy and December 31, 2019, for safety. Patients were followed after treatment discontinuation for incidence of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML); MDS/AML are reported as of April 12, 2022.

Results

Median follow-up was 77.0 months as of the efficacy data cutoff. In the ITT population, death events had occurred in 410/564 (72.7%) patients. PFS2 and OS are presented in the table 1. Among placebo-arm patients, ≈45% received a PARP inhibitor as a subsequent treatment. Safety was consistent with prior reports; MDS/AML was reported in 14 (3.8%) rucaparib-arm and 6 (3.2%) placebo-arm patients (P=0.72) (reported post-study drug treatment in 8 cases in the rucaparib arm and 6 in the placebo arm).

Conclusions

These data support the use of rucaparib as a maintenance treatment for recurrent ovarian carcinoma; although no OS benefit was seen, the PFS benefit for rucaparib was maintained through the subsequent line of therapy.

5 citations


Cited by
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Journal ArticleDOI
TL;DR: The use of maintenance therapy with olaparib provided a substantial benefit with regard to progression‐free survival among women with newly diagnosed advanced ovarian cancer and a BRCA1/2 mutation, with a 70% lower risk of disease progression or death with olAParib than with placebo.
Abstract: Background Most women with newly diagnosed advanced ovarian cancer have a relapse within 3 years after standard treatment with surgery and platinum-based chemotherapy. The benefit of the o...

1,552 citations

Journal ArticleDOI
TL;DR: In patients with advanced ovarian cancer receiving first-line standard therapy including bevacizumab, the addition of maintenance olaparib provided a significant progression-free survival benefit, which was substantial in patients with HRD-positive tumors, including those without a BRCA mutation.
Abstract: Background Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a BRCA mutation. The effect of combining mainte...

962 citations

Journal ArticleDOI
TL;DR: Urgent progress is needed to develop evidence and consensus-based treatment guidelines for each subgroup, and requires close international cooperation in conducting clinical trials through academic research groups such as the Gynecologic Cancer Intergroup.

882 citations

Journal ArticleDOI
TL;DR: The authors review the progress made to date with PARP inhibitors, describe the expanding landscape of novel anticancer therapies targeting the DNA damage response and potential predictive biomarkers, mechanisms of resistance and combinatorial strategies are discussed.
Abstract: Genomic instability is a key hallmark of cancer that arises owing to defects in the DNA damage response (DDR) and/or increased replication stress. These alterations promote the clonal evolution of cancer cells via the accumulation of driver aberrations, including gene copy-number changes, rearrangements and mutations; however, these same defects also create vulnerabilities that are relatively specific to cancer cells, which could potentially be exploited to increase the therapeutic index of anticancer treatments and thereby improve patient outcomes. The discovery that BRCA-mutant cancer cells are exquisitely sensitive to inhibition of poly(ADP-ribose) polymerase has ushered in a new era of research on biomarker-driven synthetic lethal treatment strategies for different cancers. The therapeutic landscape of antitumour agents targeting the DDR has rapidly expanded to include inhibitors of other key mediators of DNA repair and replication, such as ATM, ATR, CHK1 and CHK2, DNA-PK and WEE1. Efforts to optimize these therapies are ongoing across a range of cancers, involving the development of predictive biomarker assays of responsiveness (beyond BRCA mutations), assessment of the mechanisms underlying intrinsic and acquired resistance, and evaluation of rational, tolerable combinations with standard-of-care treatments (such as chemotherapeutics and radiation), novel molecularly targeted agents and immune-checkpoint inhibitors. In this Review, we discuss the current status of anticancer therapies targeting the DDR.

671 citations

Journal ArticleDOI
TL;DR: To improve survival in this aggressive disease, access to appropriate evidence‐based care is requisite and individualized precision medicine will require prioritizing clinical trials of innovative treatments and refining predictive biomarkers that will enable selection of patients who would benefit from chemotherapy, targeted agents, or immunotherapy.
Abstract: Ovarian cancer is the second most common cause of gynecologic cancer death in women around the world. The outcomes are complicated, because the disease is often diagnosed late and composed of several subtypes with distinct biological and molecular properties (even within the same histological subtype), and there is inconsistency in availability of and access to treatment. Upfront treatment largely relies on debulking surgery to no residual disease and platinum-based chemotherapy, with the addition of antiangiogenic agents in patients who have suboptimally debulked and stage IV disease. Major improvement in maintenance therapy has been seen by incorporating inhibitors against poly (ADP-ribose) polymerase (PARP) molecules involved in the DNA damage-repair process, which have been approved in a recurrent setting and recently in a first-line setting among women with BRCA1/BRCA2 mutations. In recognizing the challenges facing the treatment of ovarian cancer, current investigations are enlaced with deep molecular and cellular profiling. To improve survival in this aggressive disease, access to appropriate evidence-based care is requisite. In concert, realizing individualized precision medicine will require prioritizing clinical trials of innovative treatments and refining predictive biomarkers that will enable selection of patients who would benefit from chemotherapy, targeted agents, or immunotherapy. Together, a coordinated and structured approach will accelerate significant clinical and academic advancements in ovarian cancer and meaningfully change the paradigm of care.

663 citations