Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response—final results from GeparSixto

Loibl, Sibylle; Weber, Karsten E.; Timms, Kirsten M.; Elkin, Eric P.; Hahnen, Eric; Fasching, Peter A.; Lederer, Bianca; Denkert, Carsten; Schneeweiß, Andreas; Braun, Susanne; Salat, Christoph; Rezai, Mahdi; Blohmer, Jens-Uwe; Zahm, DM; Jackisch, Christian; Gerber, Bernd; Klare, Peter; Kümmel, Sherko; Schem, Christian; Paepke, Stefan; Schmutzler, Rita K.; Rhiem, Kerstin; Penn, Suzanna; Reid, Julia; Nekljudova, Valentina; Hartman, A-R; Minckwitz, Gϋnter von; Untch, Michael

doi:10.1093/annonc/mdy460

Cited by 234 publications

(201 citation statements)

References 22 publications

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“…27 The use of PARP inhibition is also being explored in patients with early-stage breast cancer and germline BRCA mutations, including in the neoadjuvant and adjuvant settings. [28][29][30][31] The randomized OlympiA phase III study will examine adjuvant use of olaparib in patients with high-risk HER2-negative breast cancer with gBRCA mutations and should reveal whether PARP inhibition can improve outcomes in breast cancer if given in an earlier setting. 31 NOTE.…”

Section: Dna Damagementioning

confidence: 99%

Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy

Gourley

Balmañà

Ledermann

et al. 2019

JCO

168

133

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The DNA damage response (DDR) pathway coordinates the identification, signaling, and repair of DNA damage caused by endogenous or exogenous factors and regulates cell-cycle progression with DNA repair to minimize DNA damage being permanently passed through cell division. Severe DNA damage that cannot be repaired may trigger apoptosis; as such, the DDR pathway is of crucial importance as a cancer target. Poly (ADP-ribose) polymerase (PARP) is the best-known element of the DDR, and several PARP inhibitors have been licensed. However, there are approximately 450 proteins involved in DDR, and a number of these other targets are being investigated in the laboratory and clinic. We review the most recent evidence for the clinical effect of PARP inhibition in breast and ovarian cancer and explore expansion into the first-line setting and into other tumor types. We critique the evidence for patient selection techniques and summarize what is known about mechanisms of PARP inhibitor resistance. We then discuss what is known about the preclinical rationale for targeting other members of the DDR pathway and the associated tumor cell genetics that may confer sensitivity to these agents. Examples include DNA damage sensors (MLH1), damage signaling molecules (ataxia-telangiectasia mutated; ataxia-telangiectasia mutated–related and Rad3-related; CHK1/2; DNA-dependent protein kinase, catalytic subunit; WEE1; CDC7), or effector proteins for repair (POLQ [also referred to as POLθ], RAD51, poly [ADP-ribose] glycohydrolase). Early-phase clinical trials targeting some of these molecules, either as a single agent or in combination, are discussed. Finally, we outline the challenges that must be addressed to maximize the therapeutic opportunity that targeting DDR provides.

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Section: Dna Damagementioning

confidence: 99%

Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy

Gourley

Balmañà

Ledermann

et al. 2019

JCO

168

133

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“…The results of this study strongly suggested that TNBC patients with HRD positive status treated with platinum-based NACT achieved more favorable response rates both in terms of pCR and residual cancer burden (RCB) compared to negative ones [28][29][30]. Similarly, in a retrospective analysis of Geparsixto, HRD TNBC patients randomized in the carboplatin arm achieved doubled pCR rates versus the non-HRD subgroup (63% and 29%, respectively), albeit without significant advantage in DFS or overall survival (OS) [31]. All these studies proved a strong correlation between HRD status and responsiveness to platinum-based NACT among TNBC patients.…”

Section: Brca1/2 Mutationsmentioning

confidence: 99%

Early Triple Negative Breast Cancer: Conventional Treatment and Emerging Therapeutic Landscapes

Diana

Carlino

Franzese

et al. 2020

Cancers

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Triple negative breast cancers (TNBCs) are characterized by worse prognosis, higher propensity to earlier metastases, and shorter survival after recurrence compared with other breast cancer subtypes. Anthracycline- and taxane-based chemotherapy is still the mainstay of treatment in early stages, although several escalation approaches have been evaluated to improve survival outcomes. The addition of platinum salts to standard neoadjuvant chemotherapy (NACT) remains controversial due to the lack of clear survival advantage, and the use of adjuvant capecitabine represents a valid treatment option in TNBC patients with residual disease after NACT. Recently, several clinical trials showed promising results through the use of poly ADP-ribose polymerase (PARP) inhibitors and by incorporating immunotherapy with chemotherapy, enriching treatment options beyond conventional cytotoxic agents. In this review, we provided an overview on the current standard of care and a comprehensive update of the recent advances in the management of early stage TNBC and focused on the latest emerging biomarkers and their clinical application to select the best therapeutic strategy in this hard-to-treat population.

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“…В нескольких клинических испытаниях изучалось, улучшает ли исходная химиотерапия на основе платины результаты при ТНРМЖ [9] (Gepasixto, 2018; исследование BRIGHTNESS). Исследования НСТ последовательно показывают, что добавление химиотерапии на основе платины увеличивает частоту полного патоморфологического ответа при ТНРМЖ, хотя влияние на долговременное рецидивирование заболевания остается менее определенным, особенно если в лечение уже включен другой алкилирующий агент (т. е. циклофосфамид) [10]. Панель экспертов проголосовала против рутинного включения платины у пациенток с уже назначенными режимами химиотерапии алкилирующими препаратами, таксанами и на основе антрациклинов.…”

Section: опухоли женской репродуктивной системы Tumors Of Female Reprunclassified

General recommendations for the management of breast cancer (St. Gallen Expert Consensus developed at the 16<sup>th </sup>th International Breast Cancer Conference)

Семиглазов

Палтуев

Семиглазов

2020

Opuholi ženskoj reproduktivnoj sistemy

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Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response—final results from GeparSixto

Abstract: The addition of carboplatin to neoadjuvant PM improved DFS significantly in TNBC. Long-term survival analyses support the neoadjuvant use of carboplatin in TNBC. HR deficiency in TNBC and HRD score in non-tmBRCA TNBC are predictors of response. HRD does not predict for carboplatin benefit.

Cited by 234 publications

References 22 publications

Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy

Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy

Early Triple Negative Breast Cancer: Conventional Treatment and Emerging Therapeutic Landscapes

General recommendations for the management of breast cancer (St. Gallen Expert Consensus developed at the 16<sup>th </sup>th International Breast Cancer Conference)

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