Search

In the KEYNOTE-355 (KN355) trial, pembrolizumab in combination with chemotherapy demonstrated superior efficacy and manageable safety compared with chemotherapy alone in patients with previously untreated locally recurrent inoperable and metastatic triple-negative breast cancer (mTNBC) with PD-L1 positive (Combined Positive Score [CPS]≥ 10) tumours. This study aimed to evaluate the clinical benefits and risks of pembrolizumab measured by quality-adjusted survival in the trial population.The study used data from the final analysis of KN355. The Quality-adjusted Time Without Symptoms of disease progression or Toxicity of treatment (Q-TWiST) analysis was used to compare treatments of pembrolizumab plus chemotherapy versus chemotherapy alone. Patients' survival time was partitioned into three health states - toxicity before disease progression (TOX), time without symptoms or toxicity before disease progression (TWiST), and relapse (REL). Utilities for these health states were estimated using EuroQol-5 Dimensions, 3 Levels (EQ-5D-3L) data collected in KN355. Q-TWiST was derived as the utility-weighted sum of the mean health state durations.Patients randomised to pembrolizumab plus chemotherapy had 3.7 months greater Q-TWiST (relative gain of 18%; P = 0.003) compared to those randomised to chemotherapy at the median follow-up of 44 months, and 4.3 months greater Q-TWiST (relative gain of 20%; P = 0.004) at the maximum follow-up of 52 months. The Q-TWiST gain increased with longer follow-up time.Pembrolizumab plus chemotherapy was associated with statistically significant and clinically important improvement in Q-TWiST compared to chemotherapy in previously untreated PD-L1-positive mTNBC.

Supplemental Tables 1-2. Table S1. Main characteristics of trials included in the analysis. Table S2. Sensitivity analysis: Subgroup comparisons of HR for EFS and OS. Supplemental Figures 1-2. Figure S1. Study selection chart. Figure S2. Survival curves of EFS and OS derived from the meta-analysis by pCR status and adjuvant therapy use.

Pathologic complete response (pCR) following neoadjuvant therapy has been associated with improved event-free survival (EFS) and overall survival (OS) in early-stage breast cancer. The magnitude of this association varies by breast cancer subtype, yet further research focusing on subtype-specific populations is limited. Here we provide an updated and comprehensive evaluation of the association between pCR and survival outcomes in triple-negative breast cancer (TNBC). A literature review identified neoadjuvant studies, including clinical trials, real-world cohort studies, and studies that pooled multiple trials or cohorts, which reported EFS/OS results by pCR in patients with early-stage TNBC. Meta-analyses were performed to evaluate the association between pCR and EFS/OS and to predict long-term survival outcomes based on pCR status. Sensitivity analyses were conducted to assess the impact of cross-study variations. Twenty-five studies with over 4,000 patients with TNBC were identified. A synthesis of evidence from these studies suggested substantial improvement in EFS and OS for pCR versus non-pCR [EFS HR (95% confidence interval): 0.24 (0.20–0.29); OS: 0.19 (0.15–0.24)]; consistent results were reported in sensitivity analyses. Collectively, our findings suggest that adjuvant therapy is associated with improved EFS/OS in patients with TNBC who received neoadjuvant therapy, regardless of pCR status.

Triple-negative breast cancer (TNBC) is associated with a high recurrence risk. However, the magnitude of direct and indirect costs associated with recurrence is lacking in the literature.Adults 18-65 years old diagnosed with TNBC were identified from the OptumHealth Reporting and Insights claims database (1999-2017) and stratified by recurrence. For patients with recurrence, the index date was defined as 30 days before recurrence; for patients without recurrence, it was randomly assigned based on the distribution of time between first treatments and index dates of the recurrence cohort. All-cause and breast cancer-related healthcare resource utilization (HRU), direct and indirect costs, and work loss up to 1 year were compared between cohorts using generalized linear models. Kaplan-Meier analyses and Cox proportional hazards models compared the risk of leaving the workforce.Among the 2340 patients analyzed, mean age was 54 years and 75% of patients had stage 0-2 cancer. Among the 1170 patients with recurrence, 236 were categorized as having metastatic recurrence and 934 as having locoregional recurrence. Relative to patients without recurrence, those with recurrence had significantly higher all-cause and breast cancer-related HRU. For instance, adjusted incidence rates (IRs) for all-cause inpatient admissions were 3.67 and 10.19 times higher for patients with locoregional and metastatic recurrence, respectively (p 0.001). Adjusted all-cause healthcare costs were $8575/month higher for metastatic recurrence and $3609/month higher for locoregional recurrence vs. patients without recurrence (p 0.001). Adjusted IRs for work loss days were approximately two times higher for locoregional and metastatic recurrence vs. without recurrence (p 0.001). Patients with locoregional recurrence incurred $335/month more indirect costs vs. patients without recurrence; those with metastatic recurrence incurred $769/month more (p 0.05). Patients with recurrence had a 63% higher rate of leaving the work force (p = 0.003).The incremental direct and indirect economic burden associated with recurrent TNBC is substantial relative to non-recurrence.

Lay abstract This study included 308 patients with early-stage triple-negative breast cancer treated in the USA at community oncology practices. Patients were female, 18 years or older and diagnosed with stage II, IIIA or IIIB breast cancer between March 2008 and March 2016, and the breast cancer was determined to be triple negative (i.e., negative for estrogen receptors, progesterone receptors and excess HER2 protein). There were 236 patients who received neoadjuvant treatment without subsequent adjuvant treatment (the Neo group) and 72 patients who received neoadjuvant treatment followed by adjuvant treatment (the Neo + adj group). The study looked at healthcare resource use and costs of care during two time periods: from neoadjuvant treatment start date to surgery (Time 1) and after surgery to recurrence or death (Time 2). Average monthly healthcare resource use and average monthly costs of care per patient were higher in Time 1 compared with Time 2 for both groups. These results demonstrate the economic and resource burden of early-stage triple-negative breast cancer especially in the time from neoadjuvant treatment initiation until surgery.

Aim: To analyze therapy for metastatic triple-negative breast cancer (mTNBC), factors contributing to survival and costs. Patients & methods: Using 2010–2016 SEER-Medicare data, we identified women (≥65 years) with mTNBC. Results: Of 302 eligible patients, 152 (50%) received systemic therapy. In multivariable regression analyses, only age

Objective: This study evaluated the cost–effectiveness of pembrolizumab/chemotherapy combinations for previously untreated metastatic triple-negative breast cancer patients in the USA with PD-L1 combined positive score ≥10. Methods: A partitioned-survival model was developed to project health outcomes and direct medical costs over a 20-year time horizon. Efficacy and safety data were from randomized clinical trials. Comparative effectiveness of indirect comparators was assessed using network meta-analyses. A series of sensitivity analyses were performed to test the robustness of the results. Results: Pembrolizumab/chemotherapy resulted in total quality-adjusted life-year (QALY) gains of 0.70 years and incremental cost–effectiveness ratio of US$182,732/QALY compared with chemotherapy alone. The incremental cost–effectiveness ratio for pembrolizumab/nab-paclitaxel versus atezolizumab/nab-paclitaxel was US$44,157/QALY. Sensitivity analyses showed the results were robust over plausible values of model inputs. Conclusion: Pembrolizumab/chemotherapy is cost effective compared with chemotherapy as well as atezolizumab/nab-paclitaxel as first-line treatment for PD-L1-positive metastatic triple-negative breast cancer from a US payer perspective.

Background: Recurrence is common among patients with early-stage triple-negative breast cancer (ESTNBC). There is minimal real-world evidence describing the patient characteristics and clinical outcomes following recurrence among patients receiving neoadjuvant chemotherapy for ESTNBC. Methods: This retrospective, observational study aimed to describe the demographic and clinical characteristics and clinical outcomes in ESTNBC patients experiencing locoregional recurrence in the US community oncology setting in the Concerto HealthAI Definitive Oncology Dataset. Eligibility criteria included female sex, age 18+ years, diagnosis of stage II, IIIA or IIIB ESTNBC between 3/2008 and 3/2016, and receipt of definitive surgical resection following neoadjuvant systemic therapy. Descriptive methods were used to evaluate patient characteristics and treatment patterns in this population. Locoregional recurrence was defined as recurrence in the same breast and/or regional nodal recurrence as documented by the provider in the medical record. Results: Of 308 patients who received neoadjuvant treatment for ESTNBC, 27.3% patients (n=84) observed recurrence, within which 25.0% (n=21) were locoregional and 75.0% (n=63) were metastatic. All 21 patients with locoregional recurrence were 65 or younger, with mean age of 50.6 (SD 8.7) at initial diagnosis. They were primarily White (47.6%, n=10) or African American (42.9%, n=9). Over half of patients were stage II at initial diagnosis (61.9%, n=13), while 38.1% (n=8) were stage III. The majority had ductal histology (90.5%, n=19) and had Grade 3 tumors (90.5%, n=19). Of the 21 patients with locoregional recurrence, less than one-tenth (9.5%, n=2) had achieved pathologic complete response (pCR) prior to their recurrence, compared to 41.2% (n=127) of the 308 patients receiving neoadjuvant treatment. In terms of treatment following locoregional recurrence, two-thirds of patients received radiation therapy (66.6%, n=14) with median duration of 47.5 days. Over half of patients (57.1%, n=12) had mastectomy following recurrence, while 14.3% (n=3) had partial mastectomy (breast conserving surgery). Most patients (85.7%, n=18) received systemic chemotherapy after recurrence. Median duration of systemic therapy following locoregional recurrence was 108 days. Nearly one-half (47.6%, n=10) had a subsequent metastatic diagnosis and nearly one-third (28.6%, n=6) had a record of death. Median time from locoregional recurrence to metastatic diagnosis was 36.6 months, but median time from locoregional recurrence to death was not reached. Conclusions: Among patients who received neoadjuvant therapy for ESTNBC in the real-world setting, nearly 7% (n=21) experienced locoregional recurrence. Nearly one-fourth of those patients had a prior pCR which potentially suggests a higher risk of recurrence associated with ESTNBC patients. Chemotherapy was the mainstay of treatment following recurrence. Most patients also received radiation therapy and surgery, but despite those nearly one-half of the patients went on to have a subsequent metastatic diagnosis. This probably reflects the limitations of existing treatment modalities for ESTNBC patients. Future studies with a bigger sample size could confirm our findings. Our study provides some benchmark perspective to such future studies. Citation Format: Amin Haiderali, Whitney C. Rhodes, Santosh Gautam, Min Huang, Jan Sieluk, Karen E. Skinner, Lee S. Schwartzberg. Locoregional recurrence in patients with early-stage triple-negative breast cancer receiving neoadjuvant systemic therapy: Patient characteristics and clinical outcomes [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-42.

Background: Pathologic complete response (pCR) is a common efficacy endpoint in neoadjuvant therapy trials for triple-negative breast cancer (TNBC). Previous studies have shown that pCR is strongly associated with improved long-term survival outcomes, including event-free survival (EFS) and overall survival (OS). However, the trial-level associations between treatment effect on pCR and long-term survival outcomes are not well established. This study sought to evaluate these associations by incorporating more recent clinical trials in TNBC. Methods: A literature review identified published randomized controlled trials (RCTs) of neoadjuvant therapy for TNBC that reported results for both pCR and EFS/OS. Meta-regression models were performed to evaluate the association of treatment effect on pCR and EFS/OS. Sensitivity analyses were conducted to assess the impact of divergent study designs. Results: Ten comparisons from 8 RCTs (N=2,478 patients) were identified from the literature review. The log (odds ratio) of pCR was a significant predictor of the log (hazard ratio) of EFS (P=.003), with a coefficient of determination of 0.68 (95% CI, 0.41–0.95). There was a weaker association between pCR and OS (P=.18), with a coefficient of determination of 0.24 (95% CI, 0.01–0.77). Consistent results were found in the exploratory analysis and sensitivity analyses. Conclusions: This is the first study that has shown a trial-level association between pCR and survival outcomes in TNBC. By incorporating the most up-to-date RCTs, this study showed a significant trial-level association between pCR and EFS. A positive association between pCR and OS was also recorded.

Background: For patients with stage II-III early-stage triple-negative breast cancer (ESTNBC), either neoadjuvant or adjuvant administration of chemotherapy is recommended. There is limited evidence describing the real-world patient characteristics and treatment patterns among patients receiving neoadjuvant +/- adjuvant chemotherapy for ESTNBC. Methods: We conducted a retrospective observational study to describe the demographic and clinical characteristics and treatment patterns in ESTNBC patients in the US community oncology setting. Eligibility criteria included female sex, age 18+, diagnosis of stage II, IIIA or IIIB ESTNBC between 3/2008 and 3/2016, receipt of definitive surgical resection, and neoadjuvant systemic therapy with or without adjuvant systemic therapy. Descriptive methods were used to compare demographic and clinical characteristics and treatment patterns among patients who received neoadjuvant systemic therapy only (Neo) versus patients who received neoadjuvant plus adjuvant systemic therapy (Neo+Adj). Results: 308 patients were eligible for the study. There were 236 patients (76.6%) who received Neo, while 72 (23.4%) received Neo+Adj. Mean age was 52.1 (SD 11.3), with 86.4% (n=266) of patients 65 or younger. Patients were predominantly White (56.8%, n=175) followed by African American (35.7%, n=110). Demographic characteristics did not differ by treatment group. The majority of patients were stage II at initial diagnosis (66.6%, n=205) and had ductal histology (93.5%, n=288). Over half of all patients (55.8%, n=172) had mastectomy; 44.2% (n=136) had breast conservation surgery. The majority of patients (79.5%, n=245) had no comorbid conditions and most (82.8%, n=255) had grade 3 tumors. Overall, 42.2% were peri/postmenopausal (n=130) at diagnosis. Distribution of stage at diagnosis was significantly different between groups (p=0.013). The pattern of findings suggests that the Neo group had earlier stage disease. Over one-third of patients with Neo were stage IIA at diagnosis (36.0%, n=85). Nearly one-fifth of patients with Neo+Adj were stage IIIB at diagnosis (19.4%, n=14), compared to 8.5% of patients receiving Neo (n=20). A significant difference in surgery type by treatment group was observed (p=0.035). Patients with Neo had a lower rate of mastectomy (52.5%, n=124) compared to Neo+Adj (66.7%, n=48), likely as a result of earlier stage disease at presentation. Among the Neo group, the most common neoadjuvant regimen was cyclophosphamide, doxorubicin and paclitaxel (59.3%, n=140), followed by cyclophosphamide, doxorubicin and docetaxel (14.4%, n=34). Most (85.2%, n=201) patients receiving Neo received one regimen in the neoadjuvant setting, while 13.1% (n=31) received two regimens. Among the Neo+Adj group, the most common neoadjuvant regimens were cyclophosphamide, doxorubicin and paclitaxel (38.9%, n=28) and cyclophosphamide with doxorubicin (23.6%, n=17), while the most common adjuvant regimens were paclitaxel (22.2%, n=16) and capecitabine (12.5%, n=9). Most (70.8%) patients receiving Neo+Adj received one neoadjuvant regimen followed by a different adjuvant regimen. Conclusions: In this sample of real-world patients with ESTNBC, the majority of patients were diagnosed with stage II disease, with limited or no comorbidities. This evaluation of treatment patterns confirmed that real-world treatment is limited to chemotherapy, which is consistent with the NCCN guidelines. Citation Format: Whitney C Rhodes, Santosh Gautam, Amin Haiderali, Min Huang, Jan Sieluk, Karen E Skinner, Lee S Schwartzberg. Patient characteristics and real-world treatment patterns in patients with early-stage triple-negative breast cancer receiving neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-33.

Background: Standard of care treatment for early-stage triple-negative breast cancer (ESTNBC) is chemotherapy. Minimal research has examined real-world effectiveness outcomes in patients with ESTNBC. Methods: This retrospective observational study evaluated event-free survival (EFS) and overall survival (OS) in patients with ESTNBC from US community oncology practices. Eligible patients were female and age 18+ at the time of stage II, IIIA or IIIB ESTNBC diagnosis that occurred between 3/2008 and 3/2016. All eligible patients received definitive surgery following neoadjuvant systemic therapy, with or without adjuvant systemic therapy. Kaplan-Meier analysis and Cox regression models were used to evaluate EFS and OS from the start of neoadjuvant therapy. EFS events are recurrence, second primary malignancy or death, whichever occurred first. Results: Of 308 patients included in the study, 236 (76.6%) received neoadjuvant only (Neo); 72 (23.4%) received neoadjuvant plus adjuvant systemic therapy (Neo+Adj). Overall, mean age was 52.1 years (SD 11.3), 56.8% were White (n=175), 35.7% African-American (n=110), 7.4% other/undocumented (n=23). Demographic characteristics did not differ between treatment groups. Two-thirds of patients (66.6%, n=205) were stage II at diagnosis, 33.4% (n=103) were stage IIIA or IIIB at diagnosis (22.4% and 11.0%, respectively). Most (82.8%, n=255) had grade 3 tumors and 42.2% were peri/postmenopausal (n=130) at diagnosis. Evidence of pathologic complete response (pCR) was observed in 41.2% of patients (n=127), while 57.5% of patients (n=177) had residual disease, and 1.3% (n=4) had undocumented/other response status. pCR was observed in 47.5% of Neo and 20.8% of Neo+Adj patients. Median EFS for all patients was not reached while mean EFS was 55.6 months (SD 1.6). Stage at diagnosis, surgery type and BMI were significant predictors of an EFS event, with stage II patients having less risk than stage III patients (Hazard ratio [HR]: 0.496 p Median OS for all patients was not reached while mean OS was 70.3 months (SD 1.5). Stage at diagnosis, surgery type and BMI were significant predictors of OS; patients with stage II had a reduced risk of death compared to stage III patients (HR: 0.299, p Conclusions: This real-world study found that stage at diagnosis, surgery type and BMI were significant predictors of EFS and OS events from the start of neoadjuvant treatment. This study highlights the need for improved therapies to extend EFS and OS for patients with ESTNBC. Given the association between pCR and EFS and OS, further analyses will evaluate EFS and OS by pCR status for each group. Time to recurrence analyses are also planned. Citation Format: Whitney C Rhodes, Santosh Gautam, Amin Haiderali, Min Huang, Jan Sieluk, Karen E Skinner, Lee S Schwartzberg. Real-world outcomes in patients receiving neoadjuvant chemotherapy for early-stage triple-negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-12.

Triple-Negative Breast Cancer; Economic burden Cáncer de mama triple negativo; Carga económica Càncer de mama triple negatiu; Càrrega econòmica Background Triple-negative breast cancer (TNBC) accounts for 10–20% of all breast cancers (BCs). It is more commonly diagnosed in younger women and often has a less favorable prognosis compared with other BC subtypes. Objective The objective of this study was to provide a literature-based extensive overview of the economic and humanistic burden of TNBC to assist medical decisions for healthcare payers, providers, and patients. Methods A systematic literature review was performed using multiple databases, including EMBASE, MEDLINE, Econlit, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, from database inception to 16 May 2021. In addition, a targeted search was performed in the Northern Light Life Sciences Conference Abstracts database from 2016 through June 2021. The bibliographies of included articles were reviewed to identify other potentially relevant publications. Quality assessment of the included studies was conducted. Results The review identified 19 studies assessing the economic burden and 10 studies assessing the humanistic burden of TNBC. Studies varied widely in study design, settings, patient populations, and time horizons. The estimates of mean per-patient annual direct medical costs ranged from around $20,000 to over $100,000 in stage I–III TNBC and from $100,000 to $300,000 in stage IV TNBC. Healthcare costs and resource utilization increased significantly with disease recurrence, progression, and increased cancer stage or line of therapy. Compared with the costs of systemic anticancer therapy, cancer management costs comprised a larger portion of total direct costs. The estimates of indirect costs due to productivity loss ranged from $207 to $1573 per patient per month (all costs presented above were adjusted to 2021 US dollars). Cancer recurrence led to significantly reduced productivity and greater rates of leaving the workforce. A rapid deterioration of health utility associated with disease progression was observed in TNBC patients. Treatment with pembrolizumab or talazoparib showed significantly greater improvements in health-related quality of life (HRQoL) compared with chemotherapy, as measured by EORTC QLQ-C30, QLQ-BR23, and FACT-B. Conclusion TNBC is associated with a substantial economic burden on healthcare systems and societies and considerably reduced productivity and HRQoL for patients. This study synthesized the published literature on the economic and humanistic burden of TNBC and highlighted the need for continued research due to the rapidly changing landscape of TNBC care.

Lay abstract This study included 450 patients with early-stage triple-negative breast cancer treated in the USA at community oncology practices. Patients were female, 18 years or older, diagnosed with stage II, IIIA or IIIB breast cancer between March 2008 and March 2016, and the breast cancer was determined to be triple negative (i.e., negative for estrogen receptors, progesterone receptors and excess HER2 protein). The study looked at the treatments received, whether those treatments worked and the response to treatment at the time of surgery. The study findings align with findings from other studies that complete response in tissue samples is associated with improved clinical outcomes. Triple-negative breast cancer remains challenging to treat, and there is a clear need for innovation in treatment options. Intervening in the early stages of triple-negative breast cancer is critical to improving outcomes.

Objective: Pathological complete response (pCR) has been a commonly used endpoint in neoadjuvant trials for breast cancer (BC). A pooled analysis of 12 neoadjuvant BC trials by Cortazar et al (2014) reported a positive association between pCR and long-term survival outcomes among patients with general BC and certain subtypes including triple negative BC (TNBC). To update and extend the evidence to assess the association of pCR and survival outcomes in TNBC, this study reviewed and summarized cohort studies and recent clinical trials in the literature. Methods: English publications reporting association between pCR and survival outcomes among TNBC patients receiving neoadjuvant chemotherapy were searched in MEDLINE, EMBASE, Cochrane CENTRAL, and Northern Light Sciences Conference Abstracts. Full-text publications from all years and conference abstracts since year 2016 were identified. Relevant clinical trials, real-world evidence (RWE) studies, and meta-analyses were included for review and extraction. Results: Of total 1,880 publications retrieved, 35 reported association between pCR and survival outcomes for neoadjuvant TNBC (9 clinical trials, 21 RWE studies, and 5 pooled/meta-analyses). The sample size of TNBC patients varied between 25 and 1,645. Different pCR definitions were used across studies, of which absence of tumor in the breast and axillary nodes was most common (N=29). The prognostic impact of pCR was evaluated for multiple survival outcomes: overall survival (OS; N=19), disease-free survival (DFS; N=14), relapse-free survival (RFS; N=7), event-free survival (N=5), distant DFS (N = 4), and local RFS (N=2). Kaplan-Meier analysis was used to assess the association between pCR and these outcomes in 31 studies. Clear separation of survival curves in favor of pCR was observed in all the studies. Log-rank tests were conducted in 18 studies, and statistically significant association was reported in majority of them, except for 1 RWE study with small sample size (N=35) and 1 pooled analysis with a different pCR definition (absence of tumor in the breast) than most of the others. Cox proportional hazards model was used in 17 studies, wherein hazard ratios of survival outcomes comparing pCR vs non-pCR ranged from 0.08 to 0.53. Conclusions: Despite divergent study designs and pCR definitions, evidence from both clinical and real-world settings consistently suggest that pCR is a strong predictor of OS and other survival outcomes among TNBC patients.

Background: Age, race, and tumor environment are major contributors in the variance of treatment outcomes in patients (pts) with breast cancer. Few studies have evaluated outcomes in real-world pts to identify high-risk populations. We aimed to compare differences in effectiveness outcomes by race among pts with metastatic triple negative breast cancer (mTNBC). Methods: This retrospective observational study evaluated effectiveness outcomes of progression-free survival (PFS) and overall survival (OS). Eligible pts were female, age ≥18 years, and diagnosed with mTNBC between 1/1/2010 and 1/31/2016 from 9 US community oncology practices. The sample was stratified by race (White, African-American [AA], Other). Kaplan-Meier methods were used to describe time-to-event outcomes. Cox regression models were used to examine the effect of race-based groups on PFS and OS. Results: The study included 608 pts (60.2% White, 33.9% AA, 5.9% Other; mean [standard deviation] age 57.5 [13.5] years). Pt characteristics largely did not differ across groups, except AA pts appeared younger (AA: 55.3 years vs. White: 58.6 vs. Other: 58.6, p=0.015) and less likely to have brain metastasis (AA: 8.3% vs. White: 15.0% vs. Other: 19.4% p=0.034). 505 pts (83.1%) received anti-cancer treatment (treated) following mTNBC diagnosis, while 103 pts (16.9%) did not receive anti-cancer treatment (untreated). The prognosis for untreated pts who did not receive anti-cancer therapy was poor, with a median OS of 4.8 months from mTNBC diagnosis compared to 12.8 months for treated pts (p=0.030). The proportion of treated pts did not differ by race (AA: 85.0% vs. White 82.5% vs. Other: 77.8%, p=0.518). Treatment class also did not differ by race (p=0.861), with Taxane therapy being the most common treatment. Among treated pts, median PFS and median OS from the start of first line treatment were 4.2 months and 12.0 months, respectively (Table 1). AA pts had a poorer prognosis than White pts as they were more likely to have a PFS event and also more likely to have an OS event compared to White pts (Hazard Ratio [HR]: 1.24, p=0.042; HR: 1.35, p=0.006; respectively). Conclusions: This evaluation of effectiveness outcomes indicates high unmet need as 1 in 6 mTNBC pts did not receive anti-cancer treatment. Furthermore, AA race was associated with poor outcomes. AA pts had shorter PFS and OS than other pts, and were more likely to experience progression or death than White pts.; despite being younger and less likely to have brain metastasis, which are typically associated with better outcomes. Future studies should be conducted to address unmet need and health outcome disparities in high-risk populations. Table 1.Effectiveness Outcomes by Race among Treated Pts WhiteAAOtherOverallp-value*PFS, # of events/# of pts267/302163/17526/28456/5050.193PFS, Median (95% CI of Median)4.37 (3.91-5.06)3.78 (3.12-4.34)4.21 (2.24-6.12)4.18 (3.72-4.57) OS, # of events/# of pts235/302155/17520/28410/5050.004OS, Median (95% CI of Median)13.74 (12.03-16.50)9.34 (7.69-10.95)10.42 (6.58-19.89)11.97 (10.26-13.38) AA African-American; CI confidence interval; PFS progression-free survival; OS overall survival; *p-value was derived using log rank χ 2 to evaluate differences across race groups Citation Format: Skinner KE, Dufour R, Haiderali A, Huang M, Schwartzberg LS. Real-world effectiveness outcomes by race in patients with metastatic triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-10-03.

Aim: To examine real-world treatment patterns and outcomes in neoadjuvant and adjuvant settings for early-stage triple-negative breast cancer (TNBC). Patients & methods: Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified patients (≥65 years) with newly diagnosed stage II/III TNBC in 2010–2015 who had surgery plus neoadjuvant and/or adjuvant (systemic and/or radiation) therapy. Treatment, survival, healthcare resource use and costs were assessed through 2016. Results: Of 1569 patients (>99% women), 6%/74%/20% received neoadjuvant-only/adjuvant-only/both (neo + adj) therapies, respectively. Median overall survival was 23 months/not reached (NR)/78 months, with longer survival at stage II (NR/NR/78 months) than stage III (22/43/38 months). Mean per patient per month costs were $10,620 and $17,872 in neoadjuvant and adjuvant periods. Conclusion: These findings provide insights into clinical and economic outcomes for early-stage TNBC in 2010–2016.

Aim: This study examined treatment patterns and effectiveness outcomes of patients with metastatic triple-negative breast cancer (mTNBC) from US community oncology centers. Materials & methods: Eligible patients were females, aged ≥18 years, diagnosed with mTNBC between 1 January 2010 and 31 January 2016. Kaplan–Meier and Cox regression methods were used. Results: Sample comprised 608 patients with average age of 57.5 years and 505/608 patients (83.1%) received systemic treatment. Overall survival (OS) from first-line treatment found that African–American patients had shorter OS than White (9.3 vs 13.7 months; hazard ratio: 1.35; p = 0.006). Conclusion: More than 15% of women with mTNBC were not treated, indicating a high unmet need. Overall prognosis remains poor, which highlights the opportunity for newer therapies to improve progression-free survival and OS.

Aim: Evaluation of monthly cost during metastatic triple-negative breast cancer (mTNBC) treatment. Patients & methods: Retrospective electronic medical record review of US females aged ≥18 years diagnosed with mTNBC between 1 January 2010 and 31 January 2016. Mean monthly costs per patient were evaluated from start of mTNBC treatment until transfer to hospice, end of record or 3 months prior to death. Results: The mean monthly cost of first line was $21,908 for 505 treated patients; 50.2% of cost was attributable to hospitalization and emergency department visits, and 32.7% to anticancer therapy. Similar patterns were observed for subsequent lines of therapy. Conclusion: The majority of costs were attributable to hospitalization and emergency department services, suggesting a need for effective interventions to reduce utilization of costly services.

e12512 Background: In the US, triple-negative breast cancer (TNBC) represents about 10–20% of breast cancers. Current information about the clinical and economic burden of early-stage TNBC in elderly patients is lacking. Methods: We used the SEER-Medicare database to identify patients with continuous Medicare Parts A/B enrollment, ≥66 years old, newly diagnosed between 2010 - 2015 (followed until 2016) with stage II-III TNBC, who initiated systemic neoadjuvant and/or adjuvant (including chemotherapy and radiation) therapy. Overall survival (OS) and event-free survival (EFS) from diagnosis were estimated using Kaplan-Meier (KM). Healthcare costs were determined during neoadjuvant and adjuvant periods. Results: Of 1569 patients ( > 99% women), 94 (6%) received neoadjuvant therapy, 1162 (74%) received adjuvant therapy, and 313 (20%) received both (neo/adj; Table). Age and race/ethnicity distributions were comparable in the three cohorts. Primary tumor T stage was T1c/T2 for 43%, 83%, and 58% in neoadjuvant, adjuvant, and neo/adj, respectively, and T3 for 14%, 10%, and 15%, respectively. The most common systemic regimens in both neoadjuvant and adjuvant periods were a taxane +/- anthracycline; 21% and 67% of patients in adjuvant and neo/adj cohorts received radiation therapy after surgery. Most claims were for outpatient treatment; hospitalizations were uncommon. The total mean expenditures per patient per month were US$10,620 and $24,408 during neoadjuvant and adjuvant periods, respectively. Conclusions: This study provides insights into patient characteristics, as well as clinical and economic outcomes for elderly patients with early-stage TNBC, treated from 2010-2016 in the US, highlighting the high monetary burden of TNBC and poor outcomes associated with stage III patients. [Table: see text]

Our objective was to estimate the cost effectiveness of ofatumumab plus chlorambucil (OChl) versus chlorambucil in patients with chronic lymphocytic leukaemia for whom fludarabine-based therapies are considered inappropriate from the perspective of the publicly funded healthcare system in Canada. A semi-Markov model (3-month cycle length) used survival curves to govern progression-free survival (PFS) and overall survival (OS). Efficacy and safety data and health-state utility values were estimated from the COMPLEMENT-1 trial. Post-progression treatment patterns were based on clinical guidelines, Canadian treatment practices and published literature. Total and incremental expected lifetime costs (in Canadian dollars [$Can], year 2013 values), life-years and quality-adjusted life-years (QALYs) were computed. Uncertainty was assessed via deterministic and probabilistic sensitivity analyses. The discounted lifetime health and economic outcomes estimated by the model showed that, compared with chlorambucil, first-line treatment with OChl led to an increase in QALYs (0.41) and total costs ($Can27,866) and to an incremental cost-effectiveness ratio (ICER) of $Can68,647 per QALY gained. In deterministic sensitivity analyses, the ICER was most sensitive to the modelling time horizon and to the extrapolation of OS treatment effects beyond the trial duration. In probabilistic sensitivity analysis, the probability of cost effectiveness at a willingness-to-pay threshold of $Can100,000 per QALY gained was 59 %. Base-case results indicated that improved overall response and PFS for OChl compared with chlorambucil translated to improved quality-adjusted life expectancy. Sensitivity analysis suggested that OChl is likely to be cost effective subject to uncertainty associated with the presence of any long-term OS benefit and the model time horizon.

Background Neoadjuvant studies in breast cancer (BC) patients have well-demonstrated that attaining pathological complete response (pCR) is associated with improved event-free survival (EFS) and overall survival (OS); and the association is strong in triple negative BC (TNBC) subtype. This study aimed to comprehensively evaluate the association of pCR and survival outcomes in TNBC by incorporating most recent studies; and to explore the impact of different study settings, thresholds of hormone receptor positivity defining TNBC and adjuvant chemotherapy usage on this association. Methods A literature search of neoadjuvant studies in TNBC was conducted up to October 2018. Clinical trials (CTs), real-world evidence (RWE) studies and meta-analyses (MA) with EFS/OS reported by pCR outcome were included. Main analyses were restricted to pCR definition of absence of tumor in the breast and axillary nodes, which is aligned with FDA guidance. Hazard ratios (HRs) evaluating the association between pCR and EFS/OS were derived from meta-analyses using fixed-effect and random-effects models. To further quantify the association, meta-analyses were conducted to synthesize the published survival curves by pCR outcome. A random-effects frailty model was utilized to account for between-study variation. Results Four randomized CTs, 2 single-arm CTs, 18 RWE studies and 1 MA for a total of 4,330 patients with TNBC were included in this study. Achieving pCR was strongly associated with improved survival outcomes (HR of EFS: 0.26, 95% CI: 0.22-0.30; and HR of OS: 0.20, 95% CI: 0.16-0.25). HR results were similar across study settings of CTs, RWE and MA. TNBC definition and adjuvant chemotherapy use did not have significant impact on HR results. The meta-analyses showed numerically longer survival in studies that reported adjuvant chemotherapy usage compared with those which did not, irrespective of attainment of pCR. Conclusions This study confirms the strong association between pCR and survival outcomes in TNBC based on evidence synthesis from both clinical and real-world settings. In addition, this study suggests potential survival benefit of subsequent adjuvant therapy for TNBC patients who received neoadjuvant therapy. Legal entity responsible for the study Merck & Co., Inc. Funding Merck & Co., Inc. Disclosure P.A. Fasching: Advisory / Consultancy: Merck & Co., Inc. M. Huang: Full / Part-time employment: Merck & Co., Inc. J. Cortes: Advisory / Consultancy: Merck & Co., Inc. J. Zhao: Full / Part-time employment: Merck & Co., Inc. J. O’Shaughnessy: Advisory / Consultancy: Merck & Co., Inc. P. Hu: Full / Part-time employment: Merck & Co., Inc. A. Haiderali: Full / Part-time employment: Merck & CO., Inc. V. Karantza: Full / Part-time employment: Merck & Co., Inc. G. Aktan: Full / Part-time employment: Merck & Co., Inc. A. Briggs: Advisory / Consultancy: Merck & Co., Inc. S. Ramsey: Advisory / Consultancy: Merck & Co., Inc. C.Z. Qi: Advisory / Consultancy, Employee of Analysis Group, Inc., which has received consulting fees from Merck & Co., Inc.: Merck & Co., Inc. J. Xie: Advisory / Consultancy, Employee of Analysis Group, Inc., which has received consulting fees from Merck & Co., Inc.: Merck & Co., Inc. C. Gu: Advisory / Consultancy, Employee of Analysis Group, Inc., which has received consulting fees from Merck & Co., Inc.: Merck & Co., Inc. K. Qian: Advisory / Consultancy, Employee of Analysis Group, Inc., which has received consulting fees from Merck & Co., Inc.: Merck & Co., Inc. M. Yuan: Advisory / Consultancy, Employee of Analysis Group, Inc., which has received consulting fees from Merck & Co., Inc.: Merck & Co., Inc. E.Q. Wu: Advisory / Consultancy, Employee of Analysis Group, Inc., which has received consulting fees from Merck & Co., Inc.: Merck & Co., Inc.

e12554 Background: Triple-negative breast cancer is a biologically aggressive disease that accounts for 15% of all breast cancers, of which around 4-5% are metastatic (mTNBC) at diagnosis. Notably, there is no standard of care for mTNBC in the first line (1L) setting. This, in addition to higher relapse rates and poor long-term survival, warrants evaluation of real-world treatment patterns, especially in the 1L setting, to better inform on clinical outcomes. Methods: This observational, retrospective, chart review study included a cohort of twenty-six mTNBC patients from six different sites Australia, who commenced 1L treatment between July 1, 2012 and June 30, 2015. Medical records of eligible patients were abstracted using electronic case report forms after gaining relevant ethics approvals. Data on treatment patterns and clinical outcomes in the 1L setting were then collected from the index date until the end of data abstraction or death. The index date is defined as the date of initiation of 1L systemic therapy for mTNBC. Results: In the 1L setting, patients that received combination (52%) chemotherapy was slightly higher than single-agent (48%) chemotherapy. The commonest combination used was Carboplatin-Gemcitabine (12%), and the most common monotherapy was Nab-Paclitaxel (24%). The overall response rate and disease control rate were estimated to be 32% and 60% in the 1L setting. The median duration of treatment and the median time to next line of therapy were calculated to be 98 days and 12.45 (95% CI 2.79, 20.30) months respectively. Importantly, the median progression free survival (sensitivity analysis) and the median overall survival were estimated to be 3.17 (95% CI 1.91, 5.09) and 10.41 (95% CI 5.36, 16.53) months respectively. Conclusions: Chemotherapy is currently the mainstay of treatment for mTNBC. However, disease progression and chemo-related toxicities warrant stratified use of more efficacious and tolerable treatment options, especially in the 1L setting. Results from this study could be useful in comparing the efficacy and cost effectiveness of these emerging targeted and immuno-therapies outside the clinical trial setting.

Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect of chemotherapy, but it may be prevented or mitigated with medications. Uncontrolled CINV can lead to reduced quality of life and can result in increased costs (due to health care utilization and missed work). We prospectively assessed the prevalence and burden of CINV in a US population. Final analysis was performed on 178 patients, beginning chemotherapy during 2007–2008 at oncology specialty settings. Patients kept a diary recording use of antiemetic medications just before the start of chemotherapy and use of antiemetic medications, health care resources, and episodes of nausea and vomiting during the 5 days following. In addition, they completed a Functional Living Index—Emesis (FLIE) questionnaire and a Work Productivity and Assessment Inventory–Nausea and Vomiting assessment, to determine the impact of CINV on daily functioning and on work productivity, respectively. Physicians independently recorded prescribed medications and health care utilization. Of the patients, 61.2% reported experiencing CINV (34.3% with acute CINV and 58.4% with delayed CINV). Based on the FLIE assessment, 37.2% of all patients reported reduced daily functioning, and of those with poorly managed CINV, about 90% reported a significant impact on daily functioning. Total costs due to CINV were on average $778.58 per patient from the day of administration through the 5 days following the first cycle of chemotherapy; patients with more severe CINV typically had higher costs. CINV remains a significant problem among US patients, suggesting a need for more effective prophylaxis use in clinical practice.

e13116Background: Treatment options are limited to chemotherapy for patients (pts) diagnosed with mTNBC. Patients with mTNBC are known to have poorer prognosis in clinical trials than other subgrou...

e21052Background: The landscape of systemic therapy for advanced melanoma has been changing quickly, beginning in March 2011 with ipilimumab approval, followed by approvals of BRAF/MEK inhibitors, ...

The control of chemotherapy-induced nausea and vomiting (CINV) is critical in preventing poor health outcomes and increasing patient quality of life. The objective of this study was to evaluate the impact of the addition of casopitant to dual-combination therapy of dexamethasone and ondansetron on quality of life in patients receiving highly emetogenic chemotherapy (HEC). In a multicenter, double-blind, randomized, placebo-controlled, add-on trial (N = 810), patients were randomized to intravenous (IV) ondansetron/dexamethasone alone (control) or in combination with either a single 150-mg oral dose of casopitant or 3-day IV/oral casopitant. Quality of life was assessed as impact of nausea and vomiting on daily life using the Functional Living Index Emesis (FLIE) questionnaire. Patients completed the FLIE questionnaire at baseline prior to receiving chemotherapy and after completion of the first cycle of HEC. Patients in the single oral dose and 3-day IV/oral casopitant groups scored higher mean total FLIE scores (115.7 and 114.0, respectively; p ≤ 0.0332) than patients in the control group (107.5), indicating that casopitant patients experienced less impact from nausea and vomiting on daily life. The overall absolute difference in the proportion of patients reporting CINV with no impact on daily life between the single oral casopitant group and the control group was 13%; the difference between the 3-day IV/oral casopitant group and the control group was 14%. The addition of casopitant to ondansetron and dexamethasone in patients receiving HEC was significantly more effective in reducing the impact of nausea and vomiting on all daily life activities as assessed by the FLIE compared with ondansetron/dexamethasone dual therapy.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world, accounting for approximately 30% of adult leukemias. The majority of CLL patients are elderly and have co-existing medical conditions. This limits therapeutic options and precludes many from receiving the recognized standard of care regimen, fludarabine, cyclophosphamide and rituximab (FCR). A number of recent studies have evaluated alternative chemoimmunotherapies for these patients. The objective of this study was to describe patient characteristics, treatment patterns, and resource utilization for patients who are unfit for a standard fludarabine-based regimen as first-line treatment for CLL in Spain, Italy, and the UK. A retrospective chart review was undertaken at 18 sites in Spain, 16 in Italy, and 17 in the UK, to identify CLL patients who initiated treatment between January 2011 and December 2012, with a target sample size of 150 per country. Eligible patients were defined as those who initiated first-line CLL treatment that did not include fludarabine (UK and Spain) or standard-dose fludarabine (Italy) which ensured that elderly patients with comorbidities were included. The variability in definitions was due to increased use of reduced-dose fludarabine regimens in Italy for patients not otherwise suitable for a standard dose of fludarabine. Data on demographic and disease-related characteristics, treatment patterns, and health resource utilization were abstracted from diagnosis until December 2013. Among eligible patients (Spain, n=127, Italy, n=121, UK, n=94), the mean age at treatment initiation was 75.9, 73.8, and 76.8 years, respectively. In the UK, 89.4% had 2 or more comorbidities compared to 74.8% in Spain and 65.3% in Italy. In all countries, chlorambucil monotherapy was the single most common regimen, prescribed to 59.6% of patients in the UK, 38.6% in Spain, and 30.6% in Italy. Bendamustine plus rituximab was the next most common regimen in the UK (17.0%) and Italy (23.1%). In Spain, the second-most common regimen was chlorambucil plus rituximab (18.9%). In Italy, 9.9% of patients received the reduced-dose fludarabine regimen, FCR-Lite. In both Spain and the UK, 40% of patients were hospitalized during the follow-up period, compared to 27% in Italy. Emergency room use ranged from 2% in the UK to 40% in Spain. A large majority of patients in all countries utilized outpatient services and laboratory monitoring, with more frequent of visits in Spain and Italy relative to the UK. Hospitalization costs were the largest cost driver (€3284 in Spain, €1312 in Italy, €10291 in the UK). Observed differences in hospital costs across countries were due to variation in: the proportion of individuals being hospitalized, with hospitalizations less common in Italy; length of hospital stay, with a minority of long and costly hospital stays in the UK; and hospital per diem costs. In Spain, outpatient visits comprised the second largest category of costs, while in Italy the second largest category was laboratory tests. In the UK, the second largest category was hospice care, although this was heavily influenced by a small number of individuals with very lengthy hospice stays. For the majority of UK patients, outpatient care was the second-highest category of costs. In conclusion, CLL patients who initiated first-line therapy during 2011 and 2012, with a regimen that did not include fludarabine (UK and Spain) or did not contain standard-dose fludarabine (Italy), were elderly, with 2 or more comorbidities. The most frequently administered treatment was chlorambucil monotherapy. Resource utilization patterns varied across countries; while some differences may have resulted from differences in patient and disease characteristics, they likely also reflect variation in management strategies between these countries. These results provide valuable baseline data to understand the potential impact of future treatments for this patient population. Abstract 2646. Table 1.SpainItalyUK% with utilizationMean annual cost per patient (€)% with utilizationMean annual cost per patient (€)% with utilizationMean annual cost per patient (€)Hospitalization40.5328426.9131240.410291Hospice008.42055.36380Emergency room40.311515.01072.24Laboratory95.052899.052687.178Outpatient95.0116794.021968.8874Transfusions25.25117.04330.1226 Disclosures Delgado: Roche: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding; Mundipharma: Consultancy, Honoraria; Celgene: Honoraria; Novartis: Consultancy, Honoraria. Rossi:Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Raine:GSK: Employment. Haiderali:GSK: Employment.

Introduction: A systematic review of clinical trials investigating interventions used for the first-line treatment of patients with CLL who are not eligible for fludarabine-based therapy was undertaken and the feasibility of performing an adjusted indirect comparison (AIC) for OChl versus B, GA101Chl and RChl was explored. Methods: Trials were identified by a systematic review; details of the methodology can be found in abstract B1333 of Hematologica (Woods et al, 2013). The trial designs, patient populations and treatment doses were examined to identify any evident systematic differences among the trials that might be expected to result in heterogeneity. The feasibility of performing an AIC using conventional methods and also alternative methods such as matching-adjusted indirect comparison (MAIC) was evaluated. Results: The trial evidence network is presented in Figure 1. Figure 1. Evidence Network Figure 1. Evidence Network The following trials were examined in detail to assess the feasibility of conducting an AIC with Chl as the common comparator. µ COMPLEMENT-1 comparing OChl with Chl (Hillmen et al., 2013). µ Knauf et al (2009; 2010, 2012) comparing B with Chl µ CLL11 comparing RChl and GA101Chl with Chl (Goede et al., 2014). Differences were found between studies in terms of treatment regimens, study design, subject characteristics and study endpoints. There were substantial differences in the actual median total dose of Chl monotherapy received by each patient, ranging from 728 mg in COMPLEMENT-1 through 522 mg for Knauf et al. to 384 mg in CLL11. Patient inclusion and exclusion criteria differed among trials, including disease stage (no Stage A patients in Knauf et al), absence or presence of criteria for fitness for fludarabine therapy, as determined by age or co-morbidity measurements such as the Cumulative Illness Rating Scale (CIRS) scores. The COMPLEMENT-1 population was older than that studied by Knauf et al. but younger than the population in the CLL11 trial. The majority of patients had ECOG Performance Status (PS) 1 in the COMPLEMENT-1 trial but PS 0 in the Knauf et al., trial. The definitions of response also varied among trials with COMPLEMENT-1 and CLL11 using the 2008 NCI-WG criteria and Knauf et al. using the earlier 1996 criteria. Discussion: Naïve indirect comparisons are subject to a variety of confounding factors which may bias the estimates in an unpredictable direction with uncertain magnitude. There are a large number of differences between the identified trials which make adjustments for heterogeneity difficult. Different Chl monotherapy regimens have shown differing efficacy (Catovsky et al., 2011) and, there is no available evidence which might be used to calculate the magnitude of this effect. Methods such as MAIC and predictive models may overcome some of the heterogeneity between clinical trials and in some cases allow for comparisons of treatments in the absence of a common comparator. Within this set of studies, there was an insufficient set of matching variables to enable for matching and validation of the match with other variables and/or a common comparator arm. Furthermore, although these methods may account for differences in patient characteristics, they cannot adjust for other differences, such as the definition or ascertainment of endpoints. Conclusions: To avoid bias, any indirect comparison of these interventions should adequately account for heterogeneity within the evidence network, with careful consideration of the factors identified in this review. The effectiveness of these interventions in comparison to Chl in routine clinical practice may differ from the efficacy observed in the trials, particularly where the Chl regimen used in routine practice differs from that investigated in the trials. Disclosures Wolowacz: GlaxoSmithKline. Sorrel Wolowacz is a full-time employee of RTI Health Solutions, which received funding from GlaxoSmithKline group of companies to conduct this study: Research Funding. Mitchell:GlaxoSmithKline. Sarah Mitchell is a full-time employee of RTI Health Solutions, which received funding from GlaxoSmithKline group of companies to conduct this study: Research Funding. Haiderali:GSK: Employment.