302P A risk score integrating lymphocytes ratios (LRs) and lactate dehydrogenase (LDH) levels to predict prognosis in metastatic breast cancer (MBC) patients G. Pelizzari1 , L. Gerratana1 , D. Basile1 , S. Zago2 , M.G. Vitale1 , M. Bartoletti1 , C. Lisanti1 , V. Fanotto1 , C. Corvaja1 , L. Bortot1 , A. Liguori3 , M. Cinausero1 , S. Russo4 , C. Andreetta4 , M. Bonotto4 , M. Mansutti4 , A.M. Minisini4 , F. Curcio5 , G. Fasola4 , F. Puglisi6 1
Department of Medicine (DAME), University of Udine, Udine, Italy,2
Clinical Pathology, Hospital “Santa Maria degli Angeli”, Pordenone, Italy,3
Medical Oncology Unit, Department of Human Pathology "G. Barresi", AOU Policlinico G. Martino Universita di Messina, Messina, Italy,4
Department of Oncology, ASUIUD Santa Maria della Misericordia, Udine, Italy,5
Clinical Pathology Institute, ASUIUD Santa Maria della Misericordia, Udine, Italy,6
University of Udine - Udine, Italy, Department of Medical Oncology and Cancer Prevention, CRO National Cancer Institute, Aviano, Italy Background:Monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR) and LDH levels have been associated with worse prognosis in several malignan-cies, including MBC. This study aimed at exploring the prognostic impact of a novel risk score, integrating baseline LRs and LDH levels in MBC patients (pts). Methods:This retrospective study analyzed 396 consecutive pts with a diagnosis of MBC, treated between 2007 and 2017 at the Oncology Department of Udine (Italy). MLR and NLR cut-offs were previously obtained through ROC analysis using propen-sity score-matched healthy controls (Gerratana et al 2018). The LDH cut-off value (480 U/L) was chosen according to the local laboratory upper reference limit. Based on these data, an integrated LRs-LDH score (LLS) was calculated ranging from 0 (LRs and LDH low), through 1 (LRs or LDH high), to 2 (both LRs and LDH high). The prognos-tic impact of baseline LLS was investigated through Cox regression, and differences in survival were tested by log-rank test.
Results:After a median follow-up of 52.8 months, median overall survival (OS) was 30.9 months and median progression free survival (PFS) was 9.2 months. Pts with base-line elevated MLR, NLR or LDH were 64.2% (251/391), 70.8% (277/391), and 31.5% (70/222), respectively. The 78.8% (308/391) of pts had elevated LRs (MLR, NLR or both). Considering subgroup analysis, no interaction was seen between LDH and LRs. By multivariate analysis, after adjustment for molecular profiles, performance status, number of metastatic sites, central nervous system and liver involvement, a worse prog-nosis in terms of OS was seen for pts with elevated levels of both LRs and LDH (LLS 2: HR 2.41, 95% CI: 1.31-4.37, p¼.003), compared to pts with normal LRs and LDH (LLS 0). Notably, significant differences in OS were observed according to the LLS (LLS 2: median OS 19.2 months, LLS 1: median OS 43.9 months, LLS 0: median OS 54.9 months; p<.0001).
Conclusions:Baseline LLS is able to predict survival in pts with MBC and provides independent prognostic information. Prospective studies are needed to validate this novel score and to explore how it may affect different treatment strategies. Legal entity responsible for the study:University of Udine.
Funding:Has not received any funding.
Disclosure:All authors have declared no conflicts of interest.
303P EMBRACA: Comparison of efficacy and safety of talazoparib (TALA) and physician’s choice of therapy (PCT) in patients (pts) with advanced breast cancer (aBC), a germline BRCA1/2 mutation (gBRCAm), and prior platinum treatment
M. Martın1 , W. Eiermann2 , H.S. Rugo3 , J. Ettl4 , S.A. Hurvitz5 , A. Gonc¸alves6 , R. Yerushalmi7, D. Markova8, I.C. Tudor8, J.L. Blum9, A.L. Hannah10, J.K. Litton11
1
Medical Oncology, Instituto de Investigacion Sanitaria Gregorio Mara~non, CIBERONC, GEICAM, Universidad Complutense, Madrid, Spain,2
Chest Surgery, Interdisziplin€ares Onkologisches Zentrum Mu¨nchen, Munich, Germany,3
Breast Cancer Center, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA,4
Obstetrics and Gynecology, Klinikum Rechts der Isar, Technische Universit€at Mu¨nchen, Munich, Germany,5Hematology/Oncology, University of California, Los Angeles, CA, USA,
6
Medical Oncology, Institut Paoli-Calmettes, Marseille, France,7Medical Oncology, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel,8
Biostatistics, Pfizer, Inc., San Francisco, CA, USA,9
Medical Oncology, Baylor Sammons Cancer Center, Dallas, TX, USA,10
Medical Oncology, Pfizer, Inc., San Francisco, CA, USA,11
Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Background: TALA is a dual-mechanism PARP inhibitor that prevents DNA damage repair by trapping PARP on DNA, resulting in cell death in BRCA1/2-mutated cells. Methods: EMBRACA is an open-label, randomised, 2-arm phase 3 trial in which effi-cacy and safety of TALA (1 mg/day) is compared with standard single-agent PCT (cape-citabine, eribulin, gem(cape-citabine, or vinorelbine) in pts with aBC and gBRCAm. In this analysis clinical outcomes were assessed in 2 subgroups of pts who had either received prior platinum (PP) or had no prior platinum (NPP) treatment.
Results: Of 431 pts randomised, 76 had PP in any setting (46 TALA; 30 PCT) and 355 were NPP (241 TALA; 114 PCT). Mean (SD) age was 46.4 (11.15) years. Pts in all groups had received a median of 1 prior cytotoxic regimen for aBC. TALA demon-strated a statistically significant improvement in both objective response rate (odds ratio [OR] [95% CI]: PP 3.16 [0.88-15.67], P¼.0456; NPP 5.36 [2.89-9.89], P<.0001) and progression-free survival (hazard ratio [95% CI]: PP 0.76 [0.40-1.45], P¼.41; NPP 0.52 [0.39-0.71], P<.0001) compared with PCT. Mean (SD) duration of TALA therapy
was 7.2 (6.52) mo (PP) and 8.7 (7.09) mo (NPP), with 15% (PP) and 19% (NPP) of pts receiving TALA for12 mo. Median duration of response (DOR) to TALA was longest in NPP pts (5.4 mo), followed by PP pts (4.2 mo); pts receiving PCT had a DOR of approximately 3.0 mo regardless of prior platinum status. Pts on TALA achieved a clini-cal benefit rate at 24 weeks (PP 59%; NPP 71%) with OR significantly favouring TALA over PCT in both groups. Of pts receiving TALA, nausea was the most common adverse event (AE) in PP pts (59%) and anaemia in NPP pts (53%). Serious AEs occurred in both PP (33%) and NPP pts (32%) taking TALA.
Conclusions: In pts with advanced gBRCAm breast cancer, TALA demonstrated statis-tically significant improvements in clinical outcomes for both PP and NPP subgroups compared with PCT. Although TALA treatment benefitted both groups, the benefit was greater if TALA was used before platinum therapy.
Clinical trial identification: NCT01945775.
Editorial acknowledgement: Editorial and medical writing support funded by Pfizer Inc. were provided by Edwin Thrower, PhD, Mary Kacillas and Paula Stuckart of Ashfield Healthcare Communications, Middletown, Connecticut.
Legal entity responsible for the study: Pfizer, Inc.
Funding: This study was sponsored by Medivation LLC, a Pfizer company. Disclosure: M. Martın: Consulting fees: Pfizer; Fees for non-CME services received directly from commercial interests or their agents: Pfizer. H.S. Rugo: Fees for con-tracted research to the University of California: Eisai, Genentech, GSK, Lilly, Macrogenics, Merck, Novartis, OBI Pharma, Pfizer, Plexxikon; Travel: Lilly, Mylan, Puma. J. Ettl: Consulting fees: Novartis, Pfizer, Roche, Eisai; Contracted research: Celgene; Honoraria: Pfizer, Roche, Teva, and Pierre Fabre. S.A. Hurvitz: Contracted research: Amgen, Bayer, BioMarin, BI, Cascadian Therapeutics, Dignitana, Genentech/ Roche, GSK, Lilly, Medivation, Merrimack, Novartis, OBI Pharma, Pfizer, Puma Biotechnology, Sanofi; Travel: Bayer, Lilly, Novartis, and OBI Pharma. D. Markova, I.C. Tudor: Employee: Pfizer, Inc. J.L. Blum: Consulting fees: Pfizer. A.L. Hannah: Consulting fees: Basilea, Medivation/Pfizerand Nektar; Ownership interest: NeoGenomics Laboratories. J.K. Litton: Institutional-contracted research: Pfizer, Novartis, EMD-Serono, AstraZeneca, GlaxoSmithKline, Genentech; Advisory board participation: AstraZeneca and Pfizer, both uncompensated. All other authors have declared no conflicts of interest.
304P EMBRACA: Efficacy and safety in comparing talazoparib (TALA) with physician’s choice of therapy (PCT) in patients (pts) with advanced breast cancer (aBC) and a germline BRCA mutation (gBRCAm); BRCA1/ BRCA2 subgroup analysis
A. Gonc¸alves1 , W. Eiermann2 , H.S. Rugo3 , J. Ettl4 , S.A. Hurvitz5 , R. Yerushalmi6 , M. Martın7 , M. Al-Adhami8 , I.C. Tudor9 , J.L. Blum10 , A.L. Hannah11 , J.K. Litton12 1
Medical Oncology, Institut Paoli-Calmettes, Marseille, France,2
Chest Surgery, Interdisziplin€ares Onkologisches Zentrum Mu¨nchen, Munich, Germany,3
Breast Cancer Center, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA,4
Obstetrics and Gynecology, Klinikum Rechts der Isar, Technische Universit€at Mu¨nchen, Munich, Germany,5
Hematology/Oncology, University of California, Los Angeles, CA, USA,6
Medical Oncology, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel,7
Medical Oncology, Instituto de Investigacion Sanitaria Gregorio Mara~non, CIBERONC, GEICAM, Universidad Complutense, Madrid, Spain,8
Biostatistics, Pfizer Inc., Groton, CT, USA,9
Biostatistics, Pfizer, Inc., San Francisco, CA, USA,10
Medical Oncology, Baylor Sammons Cancer Center, Dallas, TX, USA,11
Medical Oncology, Pfizer, Inc., San Francisco, CA, USA,12
Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Background: TALA is a dual-mechanism PARP inhibitor that traps PARP on DNA, prevents DNA damage repair, and causes cell death in BRCA1/2-mutated cells. Methods: EMBRACA is an open-label, randomized, 2-arm phase 3 trial comparing the efficacy and safety of TALA (1 mg/day) with standard single-agent PCT (capecitabine, eribulin, gemcitabine, or vinorelbine) in pts with aBC and a gBRCAm). In this analysis clinical outcomes were assessed in BRCA1 and BRCA2 subgroups.
Results: Of 431 pts randomized, 196 were BRCA1 (133 TALA; 63 PCT), 235 were BRCA2 (154 TALA; 81 PCT). Mean (SD) age was 45.4 (11.66) years (BRCA1) and 50.4 (11.45) years (BRCA2). Pts in all groups had received a median of 1 prior cytotoxic reg-imen for aBC. TALA demonstrated a statistically significant improvement in both objective response rate (odds ratio [OR] [95% CI] BRCA1 7.01 [2.99-19.54]; BRCA2 4.15 [1.90-8.52]; both P<.0001) and progression-free survival (hazard ratio [95% CI] BRCA1 0.59 [0.39-0.90]; BRCA2 0.47 [0.32-0.70]) in BRCA1 and BRCA2 subgroups compared with PCT. Mean (SD) duration of TALA therapy was 7.5 (7.07) mo (BRCA1) and 9.2 (6.88) mo (BRCA2), with 15% (BRCA1) and 22% (BRCA2) of pts receiving TALA for12 mo. Median duration of response (DOR) to TALA was longest in BRCA2 pts (6.3 mo), followed by BRCA1 pts (4.2 mo); BRCA1 and BRCA2 pts receiving PCT had a DOR of approximately 3.0 mo. Pts on TALA achieved a clinical benefit rate at 24 weeks (BRCA1 62%; BRCA2 74%) with OR significantly favouring TALA over PCT in both groups. Of pts receiving TALA, anaemia was the most common adverse event (AE) in BRCA1 pts (56%) and fatigue in BRCA2 pts (50%). Serious AEs occurred in both BRCA1 and BRCA2 pts (32%) receiving TALA.
Conclusions: In pts with advanced gBRCAm breast cancer, TALA demonstrated statis-tically significant improvements in clinical outcomes for both BRCA1 and BRCA2 sub-groups compared with PCT.
