Germline BRCA1and BRCA2 mutations in patients with HER2-negative metastatic breast cancer (mBC) treated with first-line chemotherapy: Data from the German PRAEGNANT registry.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1048-1048
Author(s):  
Peter A. Fasching ◽  
Chunling Hu ◽  
Steven Hart ◽  
Andreas D. Hartkopf ◽  
Florin A Taran ◽  
...  
Keyword(s):  
Regression Models ◽  
Cox Regression ◽  
Brca Mutation ◽  
Statistical Significance ◽  
Brca2 Mutation ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Parp Inhibitors ◽  
First Line ◽  
Metastatic Setting

1048 Background: Germline BRCA1/2 ( gBRCA) mutations (mt) are some of the few actionable alterations in mBC patients. The PARP inhibitors olaparib/talazoparib are more effective than chemotherapy (ctx) in patients with a gBRCAmt and HER2 negative(-) mBC. In mBC patients the TNT-study suggested a better progression-free survival (PFS) for g BRCA-mt compared to patients with a gBRCA1/2 wildtype (wt) when treated with platinum and not with a taxane. Otherwise little is known about the prognostic effect of g BRCA1/2mt in mBC patients. Methods: PRAEGNANT (NCT02338167) is a prospective mBC registry with a focus on molecular biomarkers. Patients were eligible for this analysis if their mBC was HER2- and treated with ctx for the first time (referred to as first-line ctx). Hormone receptor (HR) positive patients had to have all hormone therapies exhausted. Mutation frequencies and their association with patient and tumor characteristics were analyzed. Multivariable Cox regression models were built with commonly established prognostic factors and g BRCA mutation status as predictors of PFS and overall survival (OS) from first-line ctx. Results: Out of 2932 PRAEGNANT patients, 576 were HER2- and received first-line ctx. Of those 529 patients with g BRCA genotype results and follow up information could be analyzed. 24 patients (4.5%) had a g BRCAmt (11 BRCA1, 13 BRCA2). Mutation rate in HR positive patients was 3.9% (17/432) and 7.2% (7/97) in HR negative patients. Most patients received ctx either as the first treatment in the metastatic setting or after one line of hormone therapy (n=382; 72.2%). Multivariable Cox regression models showed an adjusted hazard ratio for gBRCAmt vs. gBRCAwt patients of 0.70 (95% CI: 0.43-1.15) for PFS and of 0.41 (95% CI: 0.18-0.93) for OS. Most frequent ctx treatments were taxane (52%) or capecitabine based (21%). Additionally, the prevalence of somatic BRCA1/2 mutations in this population will be presented. Conclusions: In this HER2- mBC population under ctx g BRCA mutation rates were within the expected range of about 5%. Within the analyzed population patients with a g BRCA mutation seemed to have a better OS than patients without a mutation. PFS results pointed in the same direction without statistical significance. However, with only 24 mutations replication of these results in additional cohorts is warranted. Clinical trial information: NCT02338167.

Analysis of real-world (RW) data for metastatic breast cancer (mBC) patients (pts) with somatic BRCA1/2 (sBRCA) or other homologous recombination (HR)-pathway gene mutations (muts) treated with PARP inhibitors (PARPi).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10512-10512
Author(s):  
Felipe Batalini ◽  
Russell Madison ◽  
Dean C. Pavlick ◽  
Ethan Sokol ◽  
Tamara Snow ◽  
...  
Keyword(s):  
Cox Regression ◽  
Gene Mutations ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Parp Inhibitors ◽  
Free Survival ◽  
Pathogenic Variants ◽  
Kaplan Meier ◽  
Pathway Gene ◽  
Comprehensive Genomic Profiling

10512 Background: PARPi are approved for treatment of pts w/ HER2-negative mBC and germline BRCA1/2 (g BRCA) pathogenic or likely pathogenic variants (muts); however, clinical benefit has also been demonstrated in mBC pts w/ sBRCA or other HR-pathway gene muts. Using a RW Clinico-Genomic Database (CGDB), we assessed outcomes for pts w/ gBRCA muts compared to pts w/ either s BRCA or other HR-pathway muts treated w/ PARPi. Methods: 6,329 mBC pts from ̃280 US cancer clinics were included in the Flatiron Health (FH) -Foundation Medicine (FM) CGDB, which includes comprehensive genomic profiling (CGP) linked to de-identified, electronic health record (EHR)-derived clinical data. Eligible pts had mBC, received care in the FH network from 1/1/2011-9/1/2020, and had tissue CGP by FM. Pts classified as gBRCA: positive germline result in EHR and BRCA mut predicted germline per FM’s somatic, germline, zygosity algorithm (SGZ) (Sun et al PMID 29415044). Non-g BRCA: negative germline results in EHR and a somatic BRCA (s BRCA) mut per SGZ or BRCA wild-type w/ another HR mut per CGP result. Pts w/o a documented gBRCA result in EHR, unknown FM BRCA SGZ result, or conflicting results were excluded. RW overall survival (rwOS) and RW progression-free survival (rwPFS) from start of PARPi for pts w/ gBRCA and non- gBRCA mBC were compared using Kaplan-Meier analysis and Cox regression adjusted for mBC line number, prior platinum, age at PARPi initiation, race, and receptor status. Results: Among pts who received PARPi in the mBC setting, 44 had gBRCA and 18 had non -gBRCA: 9 s BRCA (5 BRCA1, 4 BRCA2), 4 PALB2, 2 ATM, and 1 each of ATM+CDK12, BARD1+FANCF+RAD54L, and CHEK2. Of HR muts 76% were confirmed biallelic: 33/44 gBRCA (11 unknown), 8/9 sBRCA, 3/4 PALB2, and 3/5 other (1 unknown). Neither median rwPFS nor rwOS from start of PARPi were significantly different between the non-g BRCA and g BRCA cohorts (rwPFS: 7.0 [4.6-11.3] vs 5.5 [4.3-7.2] months (mos), aHR: 1.19 [0.57 – 2.43]; rwOS: 15.0 [7.95-16.3] vs 11.5 [9.46-NA] mos, aHR: 0.85 [0.36-1.98]). For 9 pts w/ sBRCA mut, median rwPFS was 7.1 mos (range 1.4-12.4) and all pts had progressed by data cut off. Conclusions: Despite small pt numbers and limitations from RW data, our results suggest that pts w/ biallelic non-g BRCA mBC may derive similar benefit from PARPi when tumor CGP detects a s BRCA mut or germline or somatic mut in other HR-pathway genes. These findings are consistent w/ the results from TBCRC-048 (Tung et al PMID 33119476) and support further randomized trials exploring the efficacy of PARPi in this population.[Table: see text]

An open-label study of sunitinib (SU) plus exemestane (E) in the first-line treatment of hormone receptor (HR)-positive metastatic breast cancer (MBC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e12019-e12019 ◽  
Author(s):  
P. Ahlgren ◽  
M. Thirlwell ◽  
R. O’Regan ◽  
C. Mormont ◽  
L. Levesque ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Single Agent ◽  
Systemic Exposure ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Dose Finding ◽  
Synergistic Activity ◽  
First Line ◽  
Open Label ◽  
Metastatic Setting

e12019 Background: SU, an oral multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, FLT3, CSF-1R and RET has activity in heavily pretreated pts with MBC. The aromatase inhibitor (AI), E, has proven 1st-line activity that compares favorably with tamoxifen in pts with HR+ BC in the adjuvant setting (Jones et al. 2008). Combining agents that target different signaling pathways may have additive/synergistic activity; combining the AI letrozole with the anti-VEGF agent bevacizumab prolonged progression-free survival to >14 mos as 1st-line therapy for HR+ MBC (Dickler et al. 2008). An open-label, phase I, dose-finding study of first-line SU + E was conducted in HR+ MBC pts. Methods: Eligible pts (postmenopausal; female; ≥18 yrs) had an ECOG PS ≤1, LVEF ≥50% and locally recurrent (unresectable) or MBC. Exclusion criteria included HER2+ BC (unless pt had progressed after trastuzumab) and prior treatment in the metastatic setting. Pts received SU 37.5 mg/d + E 25 mg/d on a continuous daily dosing regimen; if dose-limiting toxicities (DLTs) were experienced by >1/6 pts in the first 8 wks then further pts would be enrolled at SU 25 mg/d + E 25 mg/d. Pharmacokinetic (PK) analyses were performed for each drug and the active SU metabolite SU12662. Results: As of December 2008, enrollment was completed (N=6; mean age 59 ± 11 yrs; 50% of pts had ≥3 metastatic sites). No DLTs were observed and no dose reductions were required throughout the treatment period. An overview of key data is shown below. One death occurred on study (non treatment-related Enterobacter sepsis). No treatment-related G4/5 AEs occurred. PK parameter values determined for SU and E suggested increases in the systemic exposure of both drugs when administered concurrently. Conclusions: These data indicate that SU + E was tolerable with manageable toxicities, with increases in PK parameters and a similar AE profile to that of either single agent alone. This combination should be considered in future clinical trials. [Table: see text] [Table: see text]

Prediction of benefit from treatment beyond the first line in patients with metastatic breast cancer (MBC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11565-e11565
Author(s):  
Marta Bonotto ◽  
Lorenzo Gerratana ◽  
Alessandro Minisini ◽  
Elena Poletto ◽  
Stefania Russo ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Statistical Significance ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Clinical Decision ◽  
Consecutive Series ◽  
First Line ◽  
Her2 Positive ◽  
Free Survival ◽  
The Impact

e11565 Background: Despite the availability of several therapeutic options for MBC, palliative treatments beyond 1st line lack of predictive factors that could help clinical decision making. We aimed to determine which is the impact of benefit at 1stline into the benefit from subsequent therapeutic lines. Methods: We analyzed a consecutive series of 472 MBC patients treated with chemotherapy (CT) and/or endocrine therapy (ET) at the Department of Oncology of Udine, Italy, between 2004 and 2012. We evaluated Progression Free Survival at 1st (PFS1), 2nd (PFS2), 3rd (PFS3) and 4th (PFS4) line of treatment. Three distinct analyses were conducted: the first for the lines of CT, the second for the lines of ET and the third by considering both CT and ET as a line of treatment. A PFS longer than 6 months was defined as “6-month benefit". Results: Median Overall Survival was 34.5 mo (25th – 75th percentile: 14.5 – 58.8), median overall PFS1 and PFS2 was 8.9 mo and 4.3 mo respectively. Median PFS1 and PFS2 in CT lines only was 7 mo and 3.7 mo, respectively. Median PFS1 and PFS2 in ET lines only was 9.4 mo and 4.6 mo respectively. Overall, 289 patients (63.5%) presented 6-month benefit at 1st line, 128 (40.5%) at 2nd, 76 (33.8%) at 3rd and 34 (23.3%) at 4th. Not having a 6-month benefit in overall PFS1 was associated with a lack of benefit both at 2nd line (OR=0.48; p=0.0026) and at any line beyond the 1st (OR=0.39; p< 0.0001). Taking into consideration CT lines only, not having a 6-month benefit in CT PFS1 was associated with a lack of benefit both at 2nd line (OR=0.45; p=0.0072) and at any line beyond the 1st (OR=0.43; p=0.0026). A lack of benefit at the 1st ET line was not associated with further ET outcome neither in 2nd line nor in any line beyond the 1st. Stratification according to immunophenotype highlighted a statistical significance only among HER2 positive tumors (OR=0.2; p=0.0152 in 2nd line and OR=0.14; p=0.0036 beyond 1st line). Conclusions: Our results suggest that the absence of a “6-month benefit” in PFS1 predicts a lack of benefit in subsequent therapy lines, especially in HER2 positive disease. However, a lack of benefit at first line ET appears not to be detrimental to further anti-hormonal lines.

scholarly journals Emerging Role of PARP Inhibitors in Metastatic Triple Negative Breast Cancer. Current Scenario and Future Perspectives

2021 ◽  
Vol 11 ◽  
Author(s):  
Giacomo Barchiesi ◽  
Michela Roberto ◽  
Monica Verrico ◽  
Patrizia Vici ◽  
Silverio Tomao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Metastatic Breast ◽  
Parp Inhibitors ◽  
Phase Iii ◽  
Targeted Agents

Triple negative tumors represent 15% of breast cancer and are characterized by the lack of estrogen receptors, progesterone receptor, and HER2 amplification or overexpression. Approximately 25% of patients diagnosed with triple negative breast cancer carry a germline BRCA1 or BRCA2 mutation. They have an aggressive biology, and chemotherapy has been the mainstay of treatment for a long time. Despite intensive therapies, prognosis is still poor, and many patients will eventually relapse or die due to cancer. Therefore, novel targeted agents that can increase the treatment options for this disease are urgently needed. Recently, a new class of molecules has emerged as a standard of care for patients with triple negative breast cancer and germline BRCA1 or BRCA2 mutation: poly (ADP-ribose) (PARP) inhibitors. In the first part of the review, we summarize and discuss evidence supporting the use of PARP inhibitors. Currently, two PARP inhibitors have been approved for triple negative metastatic breast cancer—olaparib and talazoparib—based on two phase III trials, which showed a progression-free survival benefit when compared to chemotherapy. Safety profile was manageable with supportive therapies and dose reductions/interruptions. In addition, other PARP inhibitors are currently under investigation, such as talazoparib, rucaparib, and veliparib. Subsequently, we will discuss the potential role of PARP inhibitors in the future. Clinical research areas are investigating PARP inhibitors in combination with other agents and are including patients without germline BRCA mutations: ongoing phase II/III studies are combining PARP inhibitors with immunotherapy, while phases I and II trials are combining PARP inhibitors with other targeted agents such as ATM and PIK3CA inhibitors. Moreover, several clinical trials are enrolling patients with somatic BRCA mutation or patients carrying mutations in genes, other than BRCA1/2, involved in the homologous recombination repair pathway (e.g., CHECK2, PALB2, RAD51, etc.).

Efficacy of eribulin in patients (pts) with metastatic breast cancer (MBC): A pooled analysis by HER2 and ER status.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 137-137
Author(s):  
Peter Kaufman ◽  
Chris Twelves ◽  
Javier Cortes ◽  
Linda T. Vahdat ◽  
Martin Olivo ◽  
...  
Keyword(s):  
Cox Regression ◽  
Advanced Disease ◽  
Statistical Significance ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
Open Label ◽  
Two Phase ◽  
The Difference ◽  
Line Setting

137 Background: Eribulin (E) has been assessed in two phase 3, open-label trials in pts with locally recurrent or MBC progressing after an anthracycline (A) and taxane (T). E significantly increased overall survival (OS) compared with treatment of physician’s choice (TPC) in one study (EMBRACE) and there was a non-significant trend for improved OS with E vs capecitabine (cape) in the other (Study 301). We present an unplanned pooled analysis of these data. Methods: In the EMBRACE trial, women had received 2–5 lines of chemotherapy for advanced disease. In this ≥ 3rd line setting, pts were randomized 2:1 to E mesylate (1.4 mg/m2 iv on days 1 and 8 every 21 days) or TPC. In study 301, pts who had received 0-2 prior chemotherapies for advanced disease were randomized 1:1 to either E (as above) or cape (1.25 g/m2orally b.i.d. days 1–14 every 21 days). We analysed OS by 2-sided stratified log-rank tests and Cox regression in the overall intent-to-treat population and in the HER2-, triple negative (TNBC) and HER2+ subgroups. Results: 1,864 pts (median age 54 yrs) were included; most had been treated in the 2nd (31.5%) or 3rd line (32.7%) MBC settings. Overall, E provided significantly improved OS vs control; this benefit was also significant in HER2− and TNBC, but not HER2+ pts (Table). E improved progression-free survival overall (4.0 vs 3.4 months, HR = 0.90, 95%CI = 0.81, 0.997, p = 0.046), in HER2– (3.7 vs 3.0 months, HR = 0.84, 95%CI = 0.74, 0.95, p = 0.006) and TNBC pts (2.8 vs 2.6 months, HR = 0.78, 95%CI = 0.63, 0.96, p= 0.018). As reported before, the E safety profile was similar in the studies. Conclusions: E significantly improved OS vs standard therapies in MBC pts with HER2− and TNBC in this pooled analysis; in pts with HER2+ disease the difference did not reach statistical significance but numbers were smaller. Clinical trial information: NCT00337103 and NCT00388726. [Table: see text]

Evaluating gender as a predictive marker for response to bevacizuamb (Bev) in metastatic colorectal carcinoma (mCRC): Pooled analysis of 3369 patients (pts) in the ARCAD database.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3539-3539
Author(s):  
Ofer Margalit ◽  
William S. Harmsen ◽  
Einat shacham-Shmueli ◽  
Molly Petersen ◽  
Ben Boursi ◽  
...  
Keyword(s):  
Cox Regression ◽  
Statistical Significance ◽  
Secondary Analysis ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Pooled Analysis ◽  
Specific Response ◽  
First Line ◽  
Significant Interaction Effect ◽  
Males And Females

3539 Background: Previous studies suggest a possible gender-specific response to Bev in mCRC, showing a benefit in males, while the effect in females is less significant. Therefore, we evaluated response to Bev according to gender. Methods: Data from 3369 mCRC patients enrolled on 4 first-line randomized trials testing Bev (2000-2007) were pooled. Association between gender and progression-free survival (PFS)/overall survival (OS) was evaluated by stratified Cox regression model, adjusted for potential confounders. Predictive value was evaluated by interaction (inter.) effect between gender and treatment. In a pre-planned secondary analysis, analyses were stratified using an age cut-point of 60 years (commonly used in breast cancer trials) to evaluate the possible role of menopausal-related effects. Results: OS was not statistically different between males and females (median OS [mOS], 18.8 vs. 17.6 months [mo], adjusted hazard ratio [HRadj], 0.93, 95% confidence interval [CI], 0.84-1.03, p, 0.15) in the overall population. Bev was associated with an improved mOS in males and females, with a 2.3 and 0.6 mo benefit, respectively, as well as an improved PFS. There was no statistically significant interaction effect between gender and treatment (see table). Further stratified by age (< vs. ≥ 60 years), Bev resulted in improved PFS and OS in both genders, at all ages, except for the effect in young females which did not reach statistical significance (see table). Conclusions: Our results confirmed the mOS benefit from addition of Bev to first-line chemotherapy in mCRC in both genders, although the benefit in females was < 1 month. For females under the age of 60, there are uncertainties for mOS benefit from addition of Bev and further evaluation is needed. [Table: see text]

Associations with response to poly (ADP-ribose) polymerase (PARP) inhibitors in metastatic breast cancer: Results of a meta-regression analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12567-e12567
Author(s):  
Alexandra Desnoyers ◽  
Ramy Saleh ◽  
Michelle Nadler ◽  
Eitan Amir
Keyword(s):  
Breast Cancer ◽  
Brca Mutation ◽  
Metastatic Breast ◽  
Parp Inhibitors ◽  
Hormone Receptor Status ◽  
Negative Association ◽  
Platinum Based Chemotherapy ◽  
Metastatic Setting ◽  
Germline Brca Mutation ◽  
Meta Regression

e12567 Background: PARP inhibitors (PARPi), when given as single agents, have modest antitumor activity in patients with advanced breast cancer and germline mutation in BRCA1 or BRCA2. It is unclear whether some subgroups derive greater benefit from treatment. Methods: Two electronic databases (MEDLINE, CENTRAL) and one registry (Clinicaltrials.gov) were searched from inception to November 2018 to identify trials of PARPi in patients with metastatic breast cancer. The response rates to PARPi were extracted and pooled. Analyses were performed for patients with a germline BRCA mutation. Meta-regression explored the influence of patient and tumor characteristics and previous chemotherapy on the objective response rate (ORR) as reported in individual studies. Analysis comprised of a linear regression weighted by individual study sample size using the weighted least squares (mixed effect) method. Quantitative significance was defined using methods described by Burnand et al. Results: Of 1855 citations, 11 studies comprising 813 patients were included in the analysis. 765 (94%) patients had a germline BRCA mutations; 48% of breast cancers were triple-negative. 76% of patients had received at least 1 previous line of chemotherapy in the metastatic setting and 30% were exposed to platinum-based chemotherapy. Pooled ORR was 47% in patients with a germline BRCA mutation. Meta-regression showed that previous chemotherapy in the metastatic setting ( = -0.94, p = 0.006), especially platinum-based chemotherapy ( = -0.89, p = 0.02) were associated with highly significant negative association with ORR. A highly quantitatively significant negative association was observed for age ( = -0.80, p = 0.10), but this did not meet statistical significance. Performance status ( = 0.44, p = 0.38) and hormone receptor status (hormone receptors positive: = 0.46, p = 0.30) were not associated with response. Conclusions: PARPi therapy is associated with lesser response in patient with prior chemotherapy exposure, especially platinum-based treatment. Younger patients may benefit more from PARPi. There was no association between ORR and hormone receptor status.

Results of a phase II randomized trial of cisplatin +/- veliparib in metastatic triple-negative breast cancer (TNBC) and/or germline BRCA-associated breast cancer (SWOG S1416).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1001-1001 ◽  
Author(s):  
Priyanka Sharma ◽  
Eve Rodler ◽  
William E. Barlow ◽  
Julie Gralow ◽  
Shannon Leigh Huggins-Puhalla ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brca Mutation ◽  
A Priori ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Parp Inhibitors ◽  
Efficacy Evaluation ◽  
Prior Therapy ◽  
Grade 3

1001 Background: PARP inhibitors(i) are effective in BRCA-mutation -associated metastatic breast cancer(MBC). However, there are no studies evaluating PARPi + platin chemotherapy in BRCA wild-type(wt) TNBC. Approximately 1/2 of BRCAwt TNBC demonstrate homologous recombination deficiency (HRD) resulting in a BRCA-like phenotype which might render them sensitive to PARPi. S1416 compared the efficacy of cisplatin plus PARPi veliparib (Vel) or placebo (P) in 3 groups of MBC: gBRCA+; BRCA-like; and non-BRCA-like. Methods: Patients (pts) with metastatic TNBC or g BRCA1/2-associated MBC, who had received < 1 line of prior therapy were treated with cisplatin (75mg/m2) plus Vel or P (300 mg po BID days 1-14), every 3 weeks. All pts underwent central gBRCA testing. A priori established multipronged biomarker panel was used to classify BRCAwt pts into BRCA-like and non-BRCA-like groups, and included myChoice HRD score, somatic BRCA1/2 mutations, BRCA1 methylation and non- BRCA1/2 HR germline mutations. Primary end-point was progression-free survival (PFS) in the three pre-defined groups; secondary end-points included objective response rate (ORR), overall survival (OS), toxicity. Results: 323/335 randomized pts were eligible for efficacy evaluation; 31% had received 1 prior chemotherapy for MBC. 248 pts were classified into the three groups: (1) 37 gBRCA+ (2) 101 BRCA-like; (3) 110 non- BRCA-like. Remaining 75 could not be classified due to missing biomarker information. In the gBRCA+ group (which reached 62% of its projected accrual), numerically better PFS was noted with Vel compared to P (HR=0.64; p=0.26) though this difference was not statistically significant. In BRCA-like group improved PFS was noted with Vel vs P (median PFS 5.7 vs 4.3 months HR=0.58; p=0.023, 1 years PFS 20% vs 7%). Numerically better OS (median OS 13.7 vs 12.1 months, HR=0.66; p=0.14) and ORR (45% vs 35%, p=0.38) were noted with Vel vs P in BRCA-like group. Non-BRCA-like group did not show benefit of veliparib for PFS (HR=0.85; p=0.43) neither did the unclassified group (HR=0.97). Grade 3/4 neutropenia (46% vs 19%) and anemia (23% vs 7%) occurred at higher frequency in Vel arm compared to P. Conclusions: Addition of Vel to cisplatin significantly improved PFS and showed a trend towards improved OS for BRCA-like advanced TNBC. Integral biomarkers used in this study identified a subgroup of BRCAwt TNBC who benefited from addition of PARPi to cisplatin; platinum plus PARPi combination should be explored further in BRCA-like TNBC. Clinical trial information: NCT02595905 .

Significantly Longer Progression-Free Survival Withnab-Paclitaxel Compared With Docetaxel As First-Line Therapy for Metastatic Breast Cancer

2009 ◽  
Vol 27 (22) ◽  
pp. 3611-3619 ◽  
Author(s):  
William J. Gradishar ◽  
Dimitry Krasnojon ◽  
Sergey Cheporov ◽  
Anatoly N. Makhson ◽  
Georgiy M. Manikhas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Antitumor Activity ◽  
Statistical Significance ◽  
Randomized Study ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Significant Prolongation

PurposeIn patients with metastatic breast cancer (MBC), nab-paclitaxel produced significantly higher antitumor activity compared with patients who received solvent-based paclitaxel. This phase II study examined the antitumor activity and safety of weekly and every 3 week (q3w) nab-paclitaxel compared with docetaxel as first-line treatment in patients with MBC.Patients and MethodsIn this randomized, multicenter study, patients (N = 302) with previously untreated MBC received nab-paclitaxel 300 mg/m2q3w, 100 mg/m2weekly, or 150 mg/m2weekly or docetaxel 100 mg/m2q3w.Resultsnab-Paclitaxel 150 mg/m2weekly demonstrated significantly longer progression-free survival (PFS) than docetaxel by both independent radiologist assessment (12.9 v 7.5 months, respectively; P = .0065) and investigator assessment (14.6 v 7.8 months, respectively; P = .012). On the basis of independent radiologist review, both 150 mg/m2(49%) and 100 mg/m2(45%) weekly of nab-paclitaxel demonstrated a higher overall response rate (ORR) than docetaxel (35%), but this did not reach statistical significance. This trend was supported by statistically significant investigator ORR for both weekly nab-paclitaxel doses versus docetaxel. nab-Paclitaxel q3w versus docetaxel was not different for PFS or ORR. On the basis of both the independent radiologist and investigator review, disease control rate was significantly higher for patients receiving either dose of weekly nab-paclitaxel compared with docetaxel. Grade 3 or 4 fatigue, neutropenia, and febrile neutropenia were less frequent in all nab-paclitaxel arms. The frequency and grade of peripheral neuropathy were similar in all arms.ConclusionThis randomized study in first-line MBC demonstrated superior efficacy and safety of weekly nab-paclitaxel compared with docetaxel, with a statistically and clinically significant prolongation of PFS (> 5 months) in patients receiving nab-paclitaxel 150 mg/m2weekly compared with docetaxel 100 mg/m2q3w.

Clinical significance of circulating tumor cells (CTCs) in hormone receptor-positive (HR+) metastatic breast cancer (MBC) patients (pts) receiving letrozole (Let) or Let plus bevacizumab (Bev): CALGB 40503 (Alliance).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1049-1049
Author(s):  
Mark Jesus Mendoza Magbanua ◽  
Oleksandr Oleksandr Savenkov ◽  
Erik Asmus ◽  
Karla V. Ballman ◽  
Janet H Scott ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Predictive Value ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Cox Regression Analysis ◽  
First Line Therapy ◽  
Study Results

1049 Background: CALGB 40503 randomized HR+ MBC postmenopausal pts to Let alone or Let+Bev as first-line therapy. Adding Bev to Let prolonged progression-free survival (PFS) but not overall survival (OS) (Dickler JCO 2016). We performed a correlative study to assess prognostic and predictive value of CTCs in this population. Methods: Blood was collected prior to initiation of treatment. CTCs were enumerated using US FDA-cleared CellSearch assay; samples with ≥5 CTCs per 7.5 mLs of blood were considered CTC-positive (CTC+). Correlation of CTCs with PFS and OS was assessed using Cox regression analysis. Median follow-up was 39 months (mo). Results: Of 343 pts treated, 294 had CTC data and were included in this analysis. Original study results that showed improved PFS (HR = 0.75; 95% CI: 0.59-0.96) but not OS (HR = 0.87; 95% CI: 0.65-1.18) in pts receiving Let+Bev compared to Let were recapitulated in this subset. In multivariable analysis, CTC+ pts (31%) had significantly reduced PFS (HR = 1.49; 95% CI: 1.12-1.97) and OS (HR = 2.08; 95% CI: 1.49-2.93) compared to CTC- pts. Moreover, CTC+ pts who did not receive Bev had worse PFS (HR = 2.31; 95% CI: 1.54-3.47) and OS (HR = 2.64; 95% CI: 1.59-4.40) (Table). CTC+ pts who received Bev had numerically longer median PFS (18.0 vs. 7.0 mo) and OS (33.6 vs. 27.1 mo) compared to CTC+ pts with no Bev; however, tests for interaction between CTC status and Bev (yes vs. no) were not statistically significant for PFS (p=0.70) or OS (p=0.84). Conclusions: CTCs were highly prognostic in this study involving addition of Bev to first-line Let in postmenopausal HR+ MBC. Further research to determine the potential predictive value of CTCs in the setting of both metastatic disease and early breast cancer is warranted. Support: U10CA180821, U10CA180882; Genentech; https://acknowledgments.alliancefound.org ; NCT00601900. Survival in HR+ MBC pts receiving Let or Let+Bev stratified by CTC status. Clinical trial information: NCT00601900. [Table: see text]

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