Dominique Spaeth

Centre d'Oncologie de Gentilly · oncology

e15140 Background: Small subsets of pts treated with targeted therapies (TT) present exceptional and unexpected response (1-10%), which could be driven and correlated by a low level of genomic alterations in genes identified as causally implicated in cancer. Conversely, the multiplication of the genomic alterations in such genes would decrease the...

Purpose The interim analysis of the phase IIIb LUCY trial demonstrated the clinical effectiveness of olaparib in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC), with median progression-free survival (PFS) of 8.11 months, which was similar to that in the olaparib...

Introduction Considering the growing interest in matched cancer treatment, our aim was to evaluate the ability of a comprehensive genomic profiling (CGP) assay to propose at least one targeted therapy given an identified genomic alteration or signature (actionability), and to collect the treatment modifications based on the CGP test results in clin...

Background: Initial TRITON2 (NCT02952534) results demonstrated the efficacy of rucaparib 600 mg BID in patients with metastatic castration-resistant prostate cancer (mCRPC) associated with a BRCA1 or BRCA2 (BRCA) or other DNA damage repair (DDR) gene alteration. Objective: To present the final data from TRITON2. Design, setting, and participant...

5521 Background: Niraparib (NI) maintenance is a standard of care in platinum-sensitive ROC. Based on pivotal randomized trials, toxicity profile appears manageable through adapted drug dosing. However, data on tolerance and feasibility for unselected patients (pts) are missing, especially regarding pts’ reported adverse events (AE). Methods: NIQOL...

Introduction: The subcutaneous (H-SC) formulation of trastuzumab was demonstrated to be as effective and safe as intravenous (H-IV) and highly preferred by patients in early breast cancer. The present randomized MetaspHER trial (NCT01810393) has been the first study assessing patient's preference in metastatic setting and we report the final analy...

Background: Talazoparib (TALA) is a highly potent, dual-mechanism PARP inhibitor that has demonstrated clinical benefit in EMBRACA Phase III trial for patients with germline BRCA1/2 (BRCA1/2)-mutated locally advanced or metastatic HER2- breast cancer. Objective: The aim of the study is to ensure the effectiveness and safety of TALA in the real-worl...

Background: Around 50% of gastric cancers are diagnosed at an advanced stage. Several chemotherapy regimens are now internationally validated. Few data are available on the routine daily management of advanced gastric or gastroesophageal junction cancers. We aimed to describe chemotherapy practices, tolerance, and efficacy overall survival (OS) an...

Background In advanced oestrogen receptor-positive, HER2-negative breast cancer, acquired resistance to aromatase inhibitors frequently stems from ESR1-mutated subclones, which might be sensitive to fulvestrant. The PADA-1 trial aimed to show the efficacy of an early change in therapy on the basis of a rising ESR1 mutation in blood (bESR1mut), whil...

Background Anti-angiogenic rechallenge with bevacizumab plus chemotherapy is effective in recurrent ovarian cancer (rOC); however, data are limited on tyrosine kinase inhibitors after progression on maintenance bevacizumab. Methods In the randomized phase II TAPAZ trial, patients with rOC during the first year of bevacizumab maintenance therapy we...

Background: Following disappointing results with PD-1/PD-L1 inhibitors in ovarian cancer, it is essential to explore other immune targets. The aim of this study is to describe the tumor immune microenvironment (TME) according to genomic instability in high grade serous ovarian carcinoma (HGSOC) patients receiving primary debulking surgery followed...

Introduction: To evaluate in real-life conditions the effectiveness and safety of a biosimilar of epoetin alpha (Retacrit®) in chemotherapy-induced anemia and the impact of iron supplementation. Methods: This was a longitudinal, observational, prospective study of 12-16 weeks conducted in 195 French centers. The primary endpoint was the achievem...

Although cemiplimab has been approved for locally advanced (la) and metastatic (m) cutaneous squamous-cell carcinomas (CSCCs), its real-life value has not yet been demonstrated. An early-access program enrolled patients with la/mCSCCs to receive cemiplimab. Endpoints were best overall response rate (BOR), progression-free survival (PFS), overall su...

Background In the phase III OlympiAD trial, olaparib significantly increased progression-free survival (PFS) compared with chemotherapy of physician's choice in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor 2 (HER2)-negative metastatic breast cancer (mBC). The phase IIIb LUCY trial assessed the clinical effectiveness o...

Background Despite standard-of-care androgen-deprivation therapy and an increasing number of treatment options, the mortality rate for prostate cancer remains high. Progress to metastatic castration-resistant prostate cancer (mCRPC) necessitates additional treatments. Abiraterone acetate plus prednisone or prednisolone (AAP) prolongs survival in ch...

Introduction Dans l’essai de phase 2 évaluant le cémiplimab (CEM) chez des patients (pts) ayant un carcinome épidermoïde cutané (CEC) localement évolué ou métastatique, le taux de meilleure réponse (TMR) était de 47 % et la survie globale (SG) à un an de 81 %. Une autorisation temporaire d’utilisation (ATU) nominative a permis à ces pts d’accéder a...

Background: Trabectedin and pegylated liposomal doxorubicin (PLD) is an effective combination therapy for platinum-sensitive recurrent ovarian cancer (ROC), particularly for disease relapsing within 6-12 months of platinum therapy. The non-interventional PROSPECTYON study evaluated trabectedin/PLD in French clinical practice. Patients and methods...

Background Metastatic prostate cancer has a 30% 5-year survival rate despite recent therapeutic advances. There is a need to improve the clinical understanding and treatment of this disease, particularly in the real-world setting and among patients who are under-represented in clinical trials.Objective We aimed to evaluate the characteristics and c...

1010 Background: The question of which is the best endocrine partner to CDK4/6 inhibitors in first line for ER+ HER2- metastatic breast cancer (MBC) remains open. ESR1 mutations might be of paramount importance, as they confer resistance to AI but not to SERD. In pts treated with first line palbociclib-AI combination (PADA-1 trial, NCT03079011), we...

Background: In ER+ HER2- metastatic breast cancer (MBC), activating mutations (mut) confer resistance to aromatase inhibitors (AI) when used as single agent. The impact of mut, when detected at baseline (prior to the initiation of therapy), on the efficacy of first line combined AI- CDK4/6 inhibitor therapy remains however unknown. Methods: The PAD...

Aim of the study: Our goal was to evaluate the impact of progression type (prostate-specific antigen [PSA] only, radiological or clinical) at initiation of first-, second- and third life-extending therapy (LET) on treatment outcomes in metastatic castration-resistant prostate cancer (mCRPC) patients, by performing a post-hoc analysis using data fr...

Background: The phase 2 TRITON2 (NCT02952534) study is evaluating the poly(ADP-ribose) polymerase inhibitor rucaparib in mCRPC patients with a deleterious germline or somatic mutation in BRCA1, BRCA2, ATM, or 1 of 12 other DNA damage repair (DDR) genes who have progressed on prior androgen receptor-directed therapy and 1 taxane-based therapy. Here...

Background: The phase 2 TRITON2 (NCT02952534) study is evaluating the poly(ADP-ribose) polymerase inhibitor rucaparib in mCRPC patients with a deleterious germline or somatic mutation in BRCA1, BRCA2, ATM, or 1 of 12 other DNA damage repair (DDR) genes who have progressed on prior androgen receptor-directed therapy and 1 taxane-based therapy. Here...

Background: Molecular targeted agents (MTA) resulted in breakthroughs in selected niches. It is often assumed that tumor regression is consecutive to an oncogenic de-addiction effect. An emerging hypothesis suggests that genomic instability may be associated with poor response to MTA. Indeed, the accumulation of defects in multiple oncogenes or tu...

3542 Background: Determination of KRAS, NRAS ( RAS) and BRAF mutations is a standard of care for the management of patients with metastatic colorectal cancer (mCRC). RAS mutations are well characterized resistance biomarkers to anti-EGFR antibodies and BRAF V600 mutations indicate poor prognosis. Tissue biopsy has traditionally been used to determi...

TPS3159 Background: Molecular targeted agents (MTA) resulted in breakthroughs in selected niches. It is often assumed that tumor regression is consecutive to an oncogenic de-addiction effect. An emerging hypothesis suggests that genomic instability may be associated with poor response to MTA. Indeed, the accumulation of defects in multiple oncogene...

290 Background: The evaluation of anticancer drugs safety currently relies on the NCI-CTCAE classification. Most often in clinical trials, attention is focused on severe adverse events (AE) i.e.grade 3 or more. However, AE of lower grades can have a significant deleterious impact, especially when recurrent or permanent. We aimed at defining a new m...

189 Background: We previously reported that cancer pain was associated with a poor prognosis in mCRPC patients (pts) treated with docetaxel (D) ( Oudard, BJU Int 2009). Asymptomatic chemo-naive pts treated with novel androgen receptor targeted agent (H) have a greater overall survival (OS) than those with mild symptoms ( Miller, Eur Urol 2018). We...

Introduction Le brigatinib est une nouvelle option thérapeutique pour les patients présentant un cancer bronchique non à petites cellules (CBNPC) métastatique avec translocation ALK. Peu de données existent sur son efficacité en dehors d’essais cliniques [1]. Méthodes BRIGALK est une étude de cohorte analysant les caractéristiques des patients tra...

Background: Most targeted therapies in cancer have reached approval based on clinical studies performed in unselected patients. Small subsets of patients present exceptional responses (ER), which could be driven by a low level of genomic alterations in genes identified as causally implicated in cancer. Methods: This is an exploratory, multicenter,...

Abstract Background: The optimal sequence of life-extending therapies in metastatic cas-tration-resistant prostate cancer (mCRPC) is unknown. Objective: To evaluate outcomes among mCRPC patients treated with docetaxel (DOC), cabazitaxel (CABA), and a novel androgen receptor–targeted agent (ART; abiraterone acetate or enzalutamide) according to th...

Background: Treatment option in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel (DOC), cabazitaxel (CABA) and new hormone therapy (NHT) is limited. Rechallenge with DOC is limited because of cumulative toxicities. This study investigated the activity and safety of CABA rechallenge in mCRPC....

Purpose: The objective of the study was to describe the occurrence of stomatitis and noninfectious lung disease in patients with metastatic renal cell carcinoma (mRCC) treated with second-line everolimus in a real-world setting. Methods: This multicenter, prospective, observational study was conducted in France by physicians with experience of t...

Background: The Prostate Cancer Registry is a prospective, international observational study that began in June 2013 and will assess the characteristics and management of > 3000 mCRPC patients (pts) in routine clinical practice for ≤ 3 years. Methods: Data were collected from men with mCRPC irrespective of treatment (tx). This interim analysis repo...

Background: The Prostate Cancer Registry is a prospective study of >3000 men with mCRPC in routine care. These patients (pts) have a high level of comorbidities which are often underrepresented in RCTs. Methods: Data were collected from pts with mCRPC irrespective of treatment (tx). Outcomes in pts with comorbidities were assessed. Results: At stud...

HannaH (NCT00950300) and PrefHer (NCT01401166) studies validated the subcutaneous (H-s.c.) formulation of trastuzumab as effective and safe as intravenous (H-i.v.) and highly preferred by patients in early breast cancer. The present randomised MetaspHer trial (NCT01810393) is the first study assessing patient's preference in metastatic setting. Me...

5028 Background: The Prostate Cancer Registry is a prospective, international observational study that began in June 2013 and will assess the characteristics and management of > 3000 mCRPC patients (pts) in routine clinical practice for ≤ 3 years. Methods: Data were collected from men with mCRPC irrespective of treatment (tx). This interim analysis...

5033 Background: Only 2 chemotherapies have shown an overall survival (OS) benefit in mCRPC: docetaxel (DOC) and CABA. In patients (pts) previously treated with a new hormonal therapy (NHT: enzalutamide or abiraterone), DOC and CABA, therapeutic options are limited. We previously reported some activity of DOC rechallenge in good responders to first...

e16537 Background: The Prostate Cancer Registry is a prospective study of >3000 men with mCRPC in routine care. These patients (pts) have a high level of comorbidities which are often underrepresented in RCTs. Methods: Data were collected from pts with mCRPC irrespective of treatment (tx). Outcomes in pts with comorbidities were assessed. Results:...

Introduction: Oral therapies have shifted the follow-up of patients with cancer from hospital to home. As a consequence, the number of incoming calls has increased. To understand the source, reasons, management and burden of calls, we underwent a French national survey. The objective was to describe the way calls are managed in oncology department...

PurposeThis report describes the results of an observational, retrospective cohort study, evaluating the use of iron sucrose (IS) and red blood cell (RBC) transfusions in patients with cancer in routine clinical practice in France. A parallel investigated cohort treated with ferric carboxymaltose (FCM) has been reported earlier. Methods Data of pat...

212 Background: The Prostate Cancer Registry is the first prospective, international observational study in mCRPC documenting characteristics and management in routine clinical practice, independent of treatment used. The study began in June 2013 enrolling > 3000 mCRPC patients (pts) followed for ≤ 3 years. Methods: Source-verified data were collec...

Background Platinum-based systemic chemotherapy is considered the backbone for management of advanced urothelial carcinomas. However there is a lack of real world data on the use of such chemotherapy regimens, on patient profiles and on management after treatment failure. Methods Fifty-one randomly selected physicians from 4 European countries reg...

Background To retrospectively assess the efficacy and safety of Vinflunine (VFL) under routine conditions and identify overall survival (OS) prognostic factors. Methods Twenty centres participated in the retrospective study (minimum 4 patients undergoing VFL treatment for advanced/metastatic UC after platinum-based regimen progression. Primary end...

Background Recommendations on erythropoiesis-stimulating agents (ESAs) for the management of chemotherapy-induced anemia (CIA) are well established (Schrijvers D et al. Ann Oncol 2010;21[suppl 5]:v244-7). Iron supplementation can further improve treatment response of CIA, particularly in the case of iron deficiency (Pedrazzoli P et al. J Clin Oncol...

Background Recommendations on erythropoiesis-stimulating agents for the management of chemotherapy-induced anemia (CIA) are well established (Schrijvers D et al. Ann Oncol 2010;21[suppl 5]:v244-7). Iron supplementation can further improve treatment response of CIA, particularly in the case of iron deficiency (Pedrazzoli P et al. J Clin Oncol 2008;2...

Background: The Prostate Cancer Registry is the first international, prospective, observational study documenting the characteristics and management of patients with mCRPC in routine clinical practice, independent of treatment prescribed. The registry aims to provide real-world insights into how different therapies are used in routine practice, inc...

Background: The 21-gene Oncotype DX Recurrence Score assay is a validated assay to help decide the appropriate treatment for estrogen receptor-positive (ER+), early-stage breast cancer (EBC) in the adjuvant setting. The choice of adjuvant treatments might vary considerably in different countries according to various treatment guidelines. This pros...

Background: Fatigue associated with chemotherapy-induced anemia (CIA) is common in patients with breast cancer, and can have adverse effects on quality of life (QoL). Erythropoiesis-stimulating agents (ESAs) reduce the need for transfusions and may improve QoL in patients with symptomatic CIA. Information on hemoglobin (Hb) levels and effects of fa...

Background Everolimus is an agent frequently associated with specific toxicities. Predictive markers of efficacy are needed to help define which patients could benefit from it. The goal of this exploratory study was to identify potential predictive biomarkers in the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) activation pathway using pr...

Aim: Erythropoiesis-stimulating agents (ESAs) such as darbepoetin alfa (DA) can be used to reduce the need for transfusions and improve QoL in patients (pts) with symptomatic chemotherapy-induced anaemia (CIA). eAQUA was a phase 4, prospective, observational study, assessing Hb outcome and fatigue-related QoL (electronic assessment) in pts with sol...

Aim: RECORD I results indicate that stomatitis and non-infectious lung disease were the most frequent AEs leading to dose reduction or treatment discontinuation with everolimus (eve). AFINITE study was designed to prospectively collect data related to these two AEs and their management in real life practice. Methods: Between 09/10 and 08/12, 284 mR...

Aim: REG is a multi-kinase inhibitor with survival benefits in pts with pretreated mCRC, as demonstrated in the phase III CORRECT study. As a result, REG has been made available for medical practice use in the US, and in the EU. However, prescribing conditions in the real-life setting are known to be less stringent than selection criteria in clinic...

The population of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) who develop central nervous system (CNS) metastases is growing. Treatment strategies in this population are highly diverse. The objective of the study was to assess health care costs for the management of HER2 positive BC with CNS metastases....